Patients with chronic hepatitis C less likely to take medications over time
* Findings point to need for interventions to help patients take drugs properly
Patients being treated for chronic hepatitis C become less likely to take their medications over time, according to a new study from the Perelman School of Medicine at the University of Pennsylvania. Since the study also showed better response to the drugs when they're taken correctly, the researchers say the findings should prompt clinicians to assess patients for barriers to medication adherence throughout their treatment, and develop strategies to help them stay on track. The study is published online this month in Annals of Internal Medicine.
"Our findings are particularly timely since many chronic hepatitis C patients are now being prescribed direct-acting antiviral drugs, which have a complex dosing regimen that may be even harder for patients to maintain than the two-drug standard therapy," said lead author Vincent Lo Re, MD, MSCE, an assistant professor of Infectious Disease and Epidemiology. "These data show us that we need to develop and test interventions to help patients be more successful at taking their medicine and have the best chance at being cured."
Literacy issues, financial hurdles, and socioeconomic problems such as unstable living situations can all hamper patients' abilities to properly maintain their drug regimen. The authors suggest that refilling patients' pill boxes for them, creating easy-to-follow dosing and refill schedules, and helping them set alarms to remind them to take their medicine may all help improve adherence.
The Penn researchers studied 5,706 chronic hepatitis C patients who had been prescribed the standard treatment for the virus -- pegylated interferon (given as a single weekly shot) and ribavirin (a twice-daily oral medicine) -- using pharmacy refill data and test results for virologic response during treatment. They found that patients who refilled their prescriptions on time had a higher likelihood of being cured of the infection. However, over the course of patients' treatment, adherence waned, and more often for ribavarin. That pattern, Lo Re notes, is similar to that among patients taking drugs for other chronic conditions, during which patients often develop so-called "pill fatigue."
The newer, more powerful direct-acting antiviral drugs, which must be taken every 8 hours, will add to the complexity, and cost, of chronic hepatitis C treatment. In addition, if the newer direct-acting antiviral drugs aren't taken properly, the hepatitis C virus may become resistant to treatment, compromising the chance of cure. Hepatitis Cis a communicable disease spread via blood, from needle-sharing during IV drug use, tattooing or piercing, or even from more casual contact like sharing razors and toothbrushes. Worldwide, approximately 180 million people have the disease, about 4 million of them in the United States.
Monitoring for and treating drug-related side effects may also be a key factor in boosting adherence, Lo Re says. The study results showed that patients who received medication for thyroid dysfunction, anemia, or low white blood cell counts - common side effects associated with hepatitis C drugs - were more likely to remain adherent to their antiviral therapy. Although those drugs added more steps into their self care, Lo Re said the resulting relief for symptoms, including depression, fatigue and irritability, and more frequent visits to health care providers typically required with administration of these drugs, may play a role in patients' ability to maintain the regimen overall.
"We know that a major barrier to adherence is side effects of these drugs. People don't feel good when they're on them," he said. "If we can identify those problems and treat them when they occur, patients may be more motivated and feel well enough to continue with their prescribed regimen."
Source: University of Pennsylvania School of Medicine
Friday, September 30, 2011
Wednesday, September 28, 2011
Updated Hepatitis C Practice Guidelines Now Available from AASLD
Short version - new AASLD HCV Practice Guidelines are now available here
Updated Hepatitis C Practice Guidelines Now Available from AASLD
ARLINGTON, Va., Sept. 28, 2011 /PRNewswire via COMTEX/ -- On Monday, September 26, 2011, the American Association for the Study of Liver Diseases published online at its journal Hepatology's website ( http://onlinelibrary.wiley.com/doi/10.1002/hep.24641/full ) an update to its practice guidelines for hepatitis C - "An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases." AASLD is the premiere organization for research and education in the area of liver disease. The authors of the update are Marc Ghany, David R. Nelson, Doris B. Strader, David L. Thomas, and Leonard B. Seeff, all of whom are thought leaders in the field of hepatology.
The guidelines are noteworthy because they address treatment of patients with hepatitis C using two recently FDA approved drugs - telaprevir and boceprevir. Both long-awaited drugs were approved by the FDA in May 2011, are direct acting antivirals (DAA), and improve cure rates for patients with hepatitis C genotype 1. In addition, both drugs are in the forefront of a wave of new drugs that will reach the market in the near future. According to AASLD President T. Jake Liang, MD, "The AASLD has been very proactive in modifying our HCV guidelines to reflect this change. Ever since we knew of the improved treatment response with the addition of DAAs, the AASLD Practice Guideline Committee has moved quickly to update the existing guideline. Just 4 months after the official approval of the first two DAAs, the updated guideline is available on the website of our journal Hepatology."
DAAs promise great hope, but AASLD has expedited the writing and review of its practice guideline because those drugs do require a level of expertise for practitioners if optimum outcomes can be reached. In addition, treatment schedules will be complex and different for each DAA. The newly approved treatment schedules have more side effects than pegylated interferon and ribavirin, and should be managed carefully. The drugs are intended for use only in combination with pegylated interfreron and ribavirin, and if not used in combination with those drugs, treatment will be ineffective and will cause emergence of antiviral-resistant mutants that could be difficult to treat subsequently.
Dr. Liang said, "The DAAs will likely change the landscape of treatment for hepatitis C. However a note of caution is necessary to remind all of us that the treatment regimens are complicated and different. They are associated with more side effects than the standard peginterferon and ribavirin combination, and therefore need careful management."
Some of the concerns noted by AASLD are:
They are only approved for use in patients with HCV genotype 1.
They are not approved for use in post-transplant recurrent HCV.
They are not approved for use in HIV/HCV coinfected patients.
They are not approved for use in children.
Gary Davis, MD, Chair of AASLD's special interest group on hepatitis C acknowledges the complexities the new DAAs pose, but is still optimistic about these recent developments and the promise of new drugs. Dr. Davis said, "Hepatologists, gastroenterologists, and others who treat patients with chronic hepatitis C now have the option of two newly approved drugs that directly interfere with the ability of the hepatitis C virus to persist in the patient. Administration of these drugs is not straight-forward and increases the complexities of patient management. The new AASLD guidelines review how and when to use these agents in the clinic. This timely document should be a great asset in the management of our patients with hepatitis C."
Dr. Liang echoes those sentiments, adding, "The approval of DAAs for treatment of hepatitis C reflects an important milestone in our efforts to combat the global public health burden of viral hepatitis."
About the American Association for the Study of Liver Diseases
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. Visit our website at aasld.org.
Media Contact: Gregory Bologna703/299-9766gbologna@aasld.org
SOURCE American Association for the Study of Liver Diseases (AASLD)
Copyright (C) 2011 PR Newswire. All rights reserved
Updated Hepatitis C Practice Guidelines Now Available from AASLD
ARLINGTON, Va., Sept. 28, 2011 /PRNewswire via COMTEX/ -- On Monday, September 26, 2011, the American Association for the Study of Liver Diseases published online at its journal Hepatology's website ( http://onlinelibrary.wiley.com/doi/10.1002/hep.24641/full ) an update to its practice guidelines for hepatitis C - "An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases." AASLD is the premiere organization for research and education in the area of liver disease. The authors of the update are Marc Ghany, David R. Nelson, Doris B. Strader, David L. Thomas, and Leonard B. Seeff, all of whom are thought leaders in the field of hepatology.
The guidelines are noteworthy because they address treatment of patients with hepatitis C using two recently FDA approved drugs - telaprevir and boceprevir. Both long-awaited drugs were approved by the FDA in May 2011, are direct acting antivirals (DAA), and improve cure rates for patients with hepatitis C genotype 1. In addition, both drugs are in the forefront of a wave of new drugs that will reach the market in the near future. According to AASLD President T. Jake Liang, MD, "The AASLD has been very proactive in modifying our HCV guidelines to reflect this change. Ever since we knew of the improved treatment response with the addition of DAAs, the AASLD Practice Guideline Committee has moved quickly to update the existing guideline. Just 4 months after the official approval of the first two DAAs, the updated guideline is available on the website of our journal Hepatology."
DAAs promise great hope, but AASLD has expedited the writing and review of its practice guideline because those drugs do require a level of expertise for practitioners if optimum outcomes can be reached. In addition, treatment schedules will be complex and different for each DAA. The newly approved treatment schedules have more side effects than pegylated interferon and ribavirin, and should be managed carefully. The drugs are intended for use only in combination with pegylated interfreron and ribavirin, and if not used in combination with those drugs, treatment will be ineffective and will cause emergence of antiviral-resistant mutants that could be difficult to treat subsequently.
Dr. Liang said, "The DAAs will likely change the landscape of treatment for hepatitis C. However a note of caution is necessary to remind all of us that the treatment regimens are complicated and different. They are associated with more side effects than the standard peginterferon and ribavirin combination, and therefore need careful management."
Some of the concerns noted by AASLD are:
They are only approved for use in patients with HCV genotype 1.
They are not approved for use in post-transplant recurrent HCV.
They are not approved for use in HIV/HCV coinfected patients.
They are not approved for use in children.
Gary Davis, MD, Chair of AASLD's special interest group on hepatitis C acknowledges the complexities the new DAAs pose, but is still optimistic about these recent developments and the promise of new drugs. Dr. Davis said, "Hepatologists, gastroenterologists, and others who treat patients with chronic hepatitis C now have the option of two newly approved drugs that directly interfere with the ability of the hepatitis C virus to persist in the patient. Administration of these drugs is not straight-forward and increases the complexities of patient management. The new AASLD guidelines review how and when to use these agents in the clinic. This timely document should be a great asset in the management of our patients with hepatitis C."
Dr. Liang echoes those sentiments, adding, "The approval of DAAs for treatment of hepatitis C reflects an important milestone in our efforts to combat the global public health burden of viral hepatitis."
About the American Association for the Study of Liver Diseases
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. Visit our website at aasld.org.
Media Contact: Gregory Bologna703/299-9766gbologna@aasld.org
SOURCE American Association for the Study of Liver Diseases (AASLD)
Copyright (C) 2011 PR Newswire. All rights reserved
Monday, September 26, 2011
Enanta's Lead NS5A Inhibitor Candidate for HCV, EDP-239, Selected as One of Windhover's Top 10 Infectious Disease Projects to Watch
Enanta's Lead NS5A Inhibitor Candidate for HCV, EDP-239, Selected as One of Windhover's Top 10 Infectious Disease Projects to Watch
WATERTOWN, Mass., Sept. 26, 2011 /PRNewswire via COMTEX/ -- Enanta Pharmaceuticals, Inc. announced today that its lead development candidate from its NS5A hepatitis C virus (HCV) inhibitor program, EDP-239, has been recognized on Windhover's list of the "Top 10 Most Interesting Infectious Disease Projects to Watch." EDP-239 was chosen by independent experts at Windhover Information and Herndon Company.
NS5A, a clinically-validated target, is a non-structural viral protein that is essential to viral replication. Research efforts have shown that targeting NS5A gives rise to profound antiviral activity, and as a result, this protein has emerged as an important target for antiviral drug development. Enanta's NS5A program and intellectual property estate in the HCV field were derived from its internal drug discovery efforts.
"Enanta appreciates Windhover's recognition of our EDP-239 program for HCV, which showcases the strength of our internal drug discovery efforts aimed against important infectious disease targets," said Jay Luly, Ph.D, president and chief executive officer, Enanta Pharmaceuticals. "We are on-track to initiate a Phase 1 clinical trial for EDP-239 in the coming months, following preclinical studies that demonstrated picomolar potency against multiple genotypes of the virus, an excellent safety profile and a preclinical pharmacokinetic profile amenable to once-a-day dosing in humans."
"Selected companies have been screened using a strict set of judging criteria for the Top 10 award and represent what our committees considered the most attractive infectious disease opportunities the industry has to offer," said David Cassak, Vice President, Content, Windhover Conferences, a division of Elsevier Business Intelligence. "Winners have met rigorous criteria, including: unmet medical need, market potential, diversity of indications, strong science, multi-level partnering opportunities (biotech and pharma), potential for new opportunities beyond initial indications and corporate stability."
About the Hepatitis C Virus
Hepatitis C is a liver disease affecting over 170 million people worldwide. The virus is spread through direct contact with the blood of an infected person. Hepatitis C increases a person's risk of developing chronic liver disease, cirrhosis, liver cancer and death. Liver disease associated with HCV infection is growing rapidly, and there is an acute need for new therapies that are safer and more effective. Specifically targeted antiviral therapies for HCV, such as NS3/4a protease and NS5A inhibitors, may have the potential to increase the proportion of patients in whom the virus can be eradicated.
About Enanta
Enanta Pharmaceuticals is a research and development company that uses its novel chemistry approach and drug discovery capabilities to create best in class small molecule drugs in the infectious disease field. Enanta is developing novel protease, NS5A, nucleoside(tide) polymerase, and cyclophilin-based inhibitors targeted against the Hepatitis C virus (HCV). Additionally, the Company has created a new class of macrolide antibiotics, called Bicyclolides, which overcomes bacterial resistance. Antibacterial focus areas include overcoming resistance to superbugs, treating respiratory tract infections, and developing intravenous and oral treatments for hospital and community MRSA infections. Enanta is a privately held company headquartered in Watertown, Mass. Enanta's news releases and other information are available on the company's web site at www.enanta.com .
For Enanta Investor Relations, please contact:Paul Mellett617-607-0761
For Enanta Public Relations, please contact MacDougall Biomedical Communications:Kari Watson508-647-0209 or kwatson@macbiocom.com
SOURCE Enanta Pharmaceuticals
Copyright (C) 2011 PR Newswire. All rights reserved
WATERTOWN, Mass., Sept. 26, 2011 /PRNewswire via COMTEX/ -- Enanta Pharmaceuticals, Inc. announced today that its lead development candidate from its NS5A hepatitis C virus (HCV) inhibitor program, EDP-239, has been recognized on Windhover's list of the "Top 10 Most Interesting Infectious Disease Projects to Watch." EDP-239 was chosen by independent experts at Windhover Information and Herndon Company.
NS5A, a clinically-validated target, is a non-structural viral protein that is essential to viral replication. Research efforts have shown that targeting NS5A gives rise to profound antiviral activity, and as a result, this protein has emerged as an important target for antiviral drug development. Enanta's NS5A program and intellectual property estate in the HCV field were derived from its internal drug discovery efforts.
"Enanta appreciates Windhover's recognition of our EDP-239 program for HCV, which showcases the strength of our internal drug discovery efforts aimed against important infectious disease targets," said Jay Luly, Ph.D, president and chief executive officer, Enanta Pharmaceuticals. "We are on-track to initiate a Phase 1 clinical trial for EDP-239 in the coming months, following preclinical studies that demonstrated picomolar potency against multiple genotypes of the virus, an excellent safety profile and a preclinical pharmacokinetic profile amenable to once-a-day dosing in humans."
"Selected companies have been screened using a strict set of judging criteria for the Top 10 award and represent what our committees considered the most attractive infectious disease opportunities the industry has to offer," said David Cassak, Vice President, Content, Windhover Conferences, a division of Elsevier Business Intelligence. "Winners have met rigorous criteria, including: unmet medical need, market potential, diversity of indications, strong science, multi-level partnering opportunities (biotech and pharma), potential for new opportunities beyond initial indications and corporate stability."
About the Hepatitis C Virus
Hepatitis C is a liver disease affecting over 170 million people worldwide. The virus is spread through direct contact with the blood of an infected person. Hepatitis C increases a person's risk of developing chronic liver disease, cirrhosis, liver cancer and death. Liver disease associated with HCV infection is growing rapidly, and there is an acute need for new therapies that are safer and more effective. Specifically targeted antiviral therapies for HCV, such as NS3/4a protease and NS5A inhibitors, may have the potential to increase the proportion of patients in whom the virus can be eradicated.
About Enanta
Enanta Pharmaceuticals is a research and development company that uses its novel chemistry approach and drug discovery capabilities to create best in class small molecule drugs in the infectious disease field. Enanta is developing novel protease, NS5A, nucleoside(tide) polymerase, and cyclophilin-based inhibitors targeted against the Hepatitis C virus (HCV). Additionally, the Company has created a new class of macrolide antibiotics, called Bicyclolides, which overcomes bacterial resistance. Antibacterial focus areas include overcoming resistance to superbugs, treating respiratory tract infections, and developing intravenous and oral treatments for hospital and community MRSA infections. Enanta is a privately held company headquartered in Watertown, Mass. Enanta's news releases and other information are available on the company's web site at www.enanta.com .
For Enanta Investor Relations, please contact:Paul Mellett617-607-0761
For Enanta Public Relations, please contact MacDougall Biomedical Communications:Kari Watson508-647-0209 or kwatson@macbiocom.com
SOURCE Enanta Pharmaceuticals
Copyright (C) 2011 PR Newswire. All rights reserved
Peregrine completes enrollment for Phase II Bavituximab trial.
Peregrine completes enrollment for it's phase II trial looking it's phosphatidylserine (PS)-targeting monoclonal antibody Bavituximab for treatment of HCV. This is a 66 Tx-naive genotype 1 trial comparing Bavituximab + RBV vs peg-INF + RBV. Peregrine is looking for EVR data Q4 2011 or Q1 2012.
Peregrine Completes Patient Enrollment in Randomized Phase II HCV Trial for Bavituximab
HCV Trial Evaluating 12 Weeks of Therapy With Bavituximab With Ribavirin; Early Virologic Response (EVR) Data Expected by End of 2011 or Early 2012
TUSTIN, CA, Sep 26, 2011 (MARKETWIRE via COMTEX) -- Peregrine Pharmaceuticals, Inc. PPHM 0.00% , a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections, today announced that it has completed patient enrollment in its second randomized Phase II clinical trial for bavituximab. In this trial, 66 patients with previously untreated genotype-1 hepatitis C virus (HCV) infection were treated with 12 weeks of ribavirin in combination with bavituximab or pegylated interferon alpha-2a. Bavituximab is a phosphatidylserine (PS)-targeting monoclonal antibody with broad therapeutic potential and also is being evaluated in randomized Phase II trials for second-line and front-line NSCLC and pancreatic cancer, as well as in several investigator-sponsored trials (ISTs) in additional oncology indications.
"Bavituximab has been generally safe and well tolerated in three prior Phase I HCV trials and we look forward to assessing its use in combination with ribavirin for patients chronically infected with HCV," said Joseph S. Shan, M.P.H., Vice President of Clinical and Regulatory Affairs of Peregrine. "Once all of the patients have completed 12 weeks of therapy, we will determine the proportion of patients achieving an early-virologic response, or EVR, and expect to report data by the end of this year or early next year."
Bavituximab may address a fundamental "immune evasion" mechanism exploited by many infectious pathogens. A growing body of published data from researchers worldwide shows that bavituximab's PS target, exposed on the surface of cells infected by viruses and protozoan parasites, suppresses the immune system's ability to fight disease. PS-targeting antibodies such as bavituximab bind to PS and block the immunosuppressive signals created by the target, thereby allowing the immune system to mount a robust immune response against the pathogen.
About the Phase II HCV Trial In this multicenter Phase II randomized trial, up to 66 patients with previously untreated genotype-1 chronic HCV infection were randomly assigned to one of three treatment arms. Patients are receiving daily oral ribavirin (1000 mg) with either weekly bavituximab (0.3 mg/kg or 3 mg/kg) or pegylated interferon alpha-2a (180 ug) for up to 12 weeks and are being tested for safety parameters and antiviral activity.
The primary endpoint of the study is the proportion of patients achieving early virologic response (EVR), an early predictor of which patients are likely to clear virus with continued treatment. EVR is defined as a greater than or equal to 2 log reduction in HCV RNA after 12 weeks of treatment. Secondary endpoints include safety, tolerability and HCV viral kinetics. For further information about this trial, please visit www.peregrinetrials.com or http://www.clinicaltrials.gov/ct2/results?term=bavituximab .
About Peregrine Pharmaceuticals Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials for the treatment of cancer and serious viral infections. The company is pursuing multiple clinical programs in cancer and hepatitis C virus infection with its lead product candidate bavituximab and novel brain cancer agent Cotara(R). Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. ( www.avidbio.com ), which provides development and biomanufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at www.peregrineinc.com .
Safe Harbor Statement: Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals' intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that the company will not be in a position to report data for the Phase II trial in by the end of the year, the risk that results from the randomized Phase II trial will not be consistent with results experienced in the earlier single-arm Phase I studies, the risk that results from the randomized Phase II trial may not support registration filings with the U.S. Food and Drug Administration, and the risk that Peregrine may not have or raise adequate financial resources to complete the planned clinical programs. Factors that could cause actual results to differ materially or otherwise adversely impact the company's ability to obtain regulatory approval for its product candidates include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in the company's SEC reports including, but not limited to, the annual report on Form 10-K for the year ended April 30, 2011 and quarterly report on Form 10-Q for the quarter ended July 31, 2011. The company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release.
Contact:
Amy Figueroa or Jay Carlson
Peregrine Pharmaceuticals
(800) 987-8256
info@peregrineinc.com
Peregrine Completes Patient Enrollment in Randomized Phase II HCV Trial for Bavituximab
HCV Trial Evaluating 12 Weeks of Therapy With Bavituximab With Ribavirin; Early Virologic Response (EVR) Data Expected by End of 2011 or Early 2012
TUSTIN, CA, Sep 26, 2011 (MARKETWIRE via COMTEX) -- Peregrine Pharmaceuticals, Inc. PPHM 0.00% , a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections, today announced that it has completed patient enrollment in its second randomized Phase II clinical trial for bavituximab. In this trial, 66 patients with previously untreated genotype-1 hepatitis C virus (HCV) infection were treated with 12 weeks of ribavirin in combination with bavituximab or pegylated interferon alpha-2a. Bavituximab is a phosphatidylserine (PS)-targeting monoclonal antibody with broad therapeutic potential and also is being evaluated in randomized Phase II trials for second-line and front-line NSCLC and pancreatic cancer, as well as in several investigator-sponsored trials (ISTs) in additional oncology indications.
"Bavituximab has been generally safe and well tolerated in three prior Phase I HCV trials and we look forward to assessing its use in combination with ribavirin for patients chronically infected with HCV," said Joseph S. Shan, M.P.H., Vice President of Clinical and Regulatory Affairs of Peregrine. "Once all of the patients have completed 12 weeks of therapy, we will determine the proportion of patients achieving an early-virologic response, or EVR, and expect to report data by the end of this year or early next year."
Bavituximab may address a fundamental "immune evasion" mechanism exploited by many infectious pathogens. A growing body of published data from researchers worldwide shows that bavituximab's PS target, exposed on the surface of cells infected by viruses and protozoan parasites, suppresses the immune system's ability to fight disease. PS-targeting antibodies such as bavituximab bind to PS and block the immunosuppressive signals created by the target, thereby allowing the immune system to mount a robust immune response against the pathogen.
About the Phase II HCV Trial In this multicenter Phase II randomized trial, up to 66 patients with previously untreated genotype-1 chronic HCV infection were randomly assigned to one of three treatment arms. Patients are receiving daily oral ribavirin (1000 mg) with either weekly bavituximab (0.3 mg/kg or 3 mg/kg) or pegylated interferon alpha-2a (180 ug) for up to 12 weeks and are being tested for safety parameters and antiviral activity.
The primary endpoint of the study is the proportion of patients achieving early virologic response (EVR), an early predictor of which patients are likely to clear virus with continued treatment. EVR is defined as a greater than or equal to 2 log reduction in HCV RNA after 12 weeks of treatment. Secondary endpoints include safety, tolerability and HCV viral kinetics. For further information about this trial, please visit www.peregrinetrials.com or http://www.clinicaltrials.gov/ct2/results?term=bavituximab .
About Peregrine Pharmaceuticals Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials for the treatment of cancer and serious viral infections. The company is pursuing multiple clinical programs in cancer and hepatitis C virus infection with its lead product candidate bavituximab and novel brain cancer agent Cotara(R). Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. ( www.avidbio.com ), which provides development and biomanufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at www.peregrineinc.com .
Safe Harbor Statement: Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals' intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that the company will not be in a position to report data for the Phase II trial in by the end of the year, the risk that results from the randomized Phase II trial will not be consistent with results experienced in the earlier single-arm Phase I studies, the risk that results from the randomized Phase II trial may not support registration filings with the U.S. Food and Drug Administration, and the risk that Peregrine may not have or raise adequate financial resources to complete the planned clinical programs. Factors that could cause actual results to differ materially or otherwise adversely impact the company's ability to obtain regulatory approval for its product candidates include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in the company's SEC reports including, but not limited to, the annual report on Form 10-K for the year ended April 30, 2011 and quarterly report on Form 10-Q for the quarter ended July 31, 2011. The company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release.
Contact:
Amy Figueroa or Jay Carlson
Peregrine Pharmaceuticals
(800) 987-8256
info@peregrineinc.com
Friday, September 23, 2011
Small Cap Network.com on Hepatitis C drug development....
The Hepatitis C Race Is On: MRK, VRTX, VRUS, ACHN, PFE, IDIX
By James E. Brumley
Published: September 21, 2011 10:24:49 AM PDT
The race for an effective hepatitis C treatment may not be as high-profile as, say efforts to find a cure for cancer or HIV. It's a bigger market than most may imagine though, judging from the number of companies doing R&D in the arena. Here's a quick look at the key one.
Merck & Co., Inc. (NYSE:MRK) has one of only two FDA-approved hepatitis C drugs. Its version is called Victrelis - a protease inhibitor. It was only approved in May, so there's no sales momentum yet. If the efficacy seen in Phase II testing is any clue though, it should be a revenue driver. Merck said two-thirds of patients receiving Victrelis in combination with other treatments had a strong virologic response in that the virus was no longer detected in the blood six months weeks after the treatment was stopped.
Vertex Pharmaceuticals Incorporated (NASDAQ:VRTX) has the other FDA-approved hepatitis C treatment. Theirs is called Incivek - another protease inhibitor. Vertex's entry in the race seems even better than Merck's; nearly 80% of patients saw no sign of the irus in the blood 24 weeks after treatment.
Pharmasset, Inc. (NASDAQ:VRUS) is anything but a household name, and its drug is only in Phase II testing. But, PSI-7977 (a nucleoside polymerase inhibitor) is very promising. When used in combination with interferon and ribavirin, Pharmasset produces a 12-week sustained virological response rate of 91% for previously untreated hepatitis C patients.
Achillion Pharmaceuticals, Inc. (NASDAQ:ACHN) actually has several versions of its treatment currently anywhere from pre-clinical studies to Phase II trials. They're all built on the same basic platform though; all act as protease inhibitors. The underlying mechanism for these compounds is novel, targeting the NS4A protein of HCV. By inhibiting this target, Achillion Pharmaceuticals says the formation of a functional replicase complex (a key step in viral replication of the viral RNA genome) is blocked. ACH-1625 is the one to watch closely now.
Update/Correction: Achillion is exploring two distinct programs - protease inhibitors and NS5A inhibitors. The protease inhibitor program includes its lead Phase 2 compound ACH-1625, while the Phase 1 program is evaluating a novel pan-genotypic compound designated ACH-2684. The second class of compounds the company is developing are NS5A inhibitors, and is the backbone ACH-2928 (also in Phase 1 development).
Pfizer Inc. (NYSE:PFE) is in the hepatitis C race, but for a company of it size and financial backing, it's surprisingly lagging. Its polymerase inhibitor (PF-868554) is only in Phase II trials right now. Given the lateness of the effort and the fact that Pfizer has multiple partners on this front, it's hard to say HCV is a priority its going to push forward in a meaningful way.
Finally, Idenix Pharmaceuticals, Inc. (NASDAQ:IDIX) has a small army of hepatitis C treatment in the hopper (four in all, but they're all significantly different than one another). The one that's furthest along is IDX184, currently in Phase II, while work on IDX320 has been halted for the time being. Idenix Pharmaceuticals began 12-week trials of IDX184 in July of this year, and is expected to share interim results sometime in the fourth quarter. IDX184 has also been halted - albeit temporary - in the past by the FDA over safety concerns.
The hepatitis C market could be worth as much as $10 billion within five years, according to industry analysts. It affects tens of million of people worldwide every year.
By James E. Brumley
Published: September 21, 2011 10:24:49 AM PDT
The race for an effective hepatitis C treatment may not be as high-profile as, say efforts to find a cure for cancer or HIV. It's a bigger market than most may imagine though, judging from the number of companies doing R&D in the arena. Here's a quick look at the key one.
Merck & Co., Inc. (NYSE:MRK) has one of only two FDA-approved hepatitis C drugs. Its version is called Victrelis - a protease inhibitor. It was only approved in May, so there's no sales momentum yet. If the efficacy seen in Phase II testing is any clue though, it should be a revenue driver. Merck said two-thirds of patients receiving Victrelis in combination with other treatments had a strong virologic response in that the virus was no longer detected in the blood six months weeks after the treatment was stopped.
Vertex Pharmaceuticals Incorporated (NASDAQ:VRTX) has the other FDA-approved hepatitis C treatment. Theirs is called Incivek - another protease inhibitor. Vertex's entry in the race seems even better than Merck's; nearly 80% of patients saw no sign of the irus in the blood 24 weeks after treatment.
Pharmasset, Inc. (NASDAQ:VRUS) is anything but a household name, and its drug is only in Phase II testing. But, PSI-7977 (a nucleoside polymerase inhibitor) is very promising. When used in combination with interferon and ribavirin, Pharmasset produces a 12-week sustained virological response rate of 91% for previously untreated hepatitis C patients.
Achillion Pharmaceuticals, Inc. (NASDAQ:ACHN) actually has several versions of its treatment currently anywhere from pre-clinical studies to Phase II trials. They're all built on the same basic platform though; all act as protease inhibitors. The underlying mechanism for these compounds is novel, targeting the NS4A protein of HCV. By inhibiting this target, Achillion Pharmaceuticals says the formation of a functional replicase complex (a key step in viral replication of the viral RNA genome) is blocked. ACH-1625 is the one to watch closely now.
Update/Correction: Achillion is exploring two distinct programs - protease inhibitors and NS5A inhibitors. The protease inhibitor program includes its lead Phase 2 compound ACH-1625, while the Phase 1 program is evaluating a novel pan-genotypic compound designated ACH-2684. The second class of compounds the company is developing are NS5A inhibitors, and is the backbone ACH-2928 (also in Phase 1 development).
Pfizer Inc. (NYSE:PFE) is in the hepatitis C race, but for a company of it size and financial backing, it's surprisingly lagging. Its polymerase inhibitor (PF-868554) is only in Phase II trials right now. Given the lateness of the effort and the fact that Pfizer has multiple partners on this front, it's hard to say HCV is a priority its going to push forward in a meaningful way.
Finally, Idenix Pharmaceuticals, Inc. (NASDAQ:IDIX) has a small army of hepatitis C treatment in the hopper (four in all, but they're all significantly different than one another). The one that's furthest along is IDX184, currently in Phase II, while work on IDX320 has been halted for the time being. Idenix Pharmaceuticals began 12-week trials of IDX184 in July of this year, and is expected to share interim results sometime in the fourth quarter. IDX184 has also been halted - albeit temporary - in the past by the FDA over safety concerns.
The hepatitis C market could be worth as much as $10 billion within five years, according to industry analysts. It affects tens of million of people worldwide every year.
Monday, September 19, 2011
BMS-790052 Phase II results demonstrate up to 83% SVR24 in study of genotype 1 HCV patients...
(Bristol Myers Squibb's NS5A replication complex inhibitor BMS-790052 + P/R continues to look very good in it's phase II trialinterim SVR24 data update from ICAAC. 83% SVR24 in this treatment-naive genotype 1 population, adverse events very comparable to the P/R control arm.)
BMS-790052 Plus Peginterferon Alfa and Ribavirin Demonstrated up to 83% Sustained Virologic Response 24 Weeks Post-Treatment (SVR24) in Phase II Study of Genotype 1 Hepatitis C Patients
In this study,adverse event profile of regimen containing BMS-790052 was consistent with that of treatment with peginterferon alfa and ribavirin plus placebo
PRINCETON, N.J., Sep 17, 2011 (BUSINESS WIRE) -- --Company has initiated Phase III development program for BMS-790052
Bristol-Myers Squibb Company BMY -0.72% today announced results from a Phase II clinical trial of 48 treatment-naive genotype 1 hepatitis C infected patients in which treatment with BMS-790052, an NS5A replication complex inhibitor, in combination with peginterferon alfa and ribavirin (pegIFNalfa/RBV) maintained undetectable viral load at 24 weeks post-treatment (SVR24) in 83% (60 mg), 83% (10 mg) and 42% (3 mg) of patients, compared with 25% of patients in the pegIFNalfa/RBV control group after 48 weeks of combination therapy. In this study, serious adverse events were reported in one patient (8.3%) from each of the BMS-790052 treatment groups and in zero patients from the control group. The data were reported today at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Chicago. The investigational direct acting antiviral BMS-790052 is now in Phase III development.
"The hepatitis C treatment landscape is rapidly evolving and although there have been positive advances recently, there remains a need for additional therapies with a more favorable efficacy and safety profile," said Stanislas Pol, MD, PhD, Professor of Hepatology at Universite Paris V (Rene Descartes), Paris, France and head of the Hepatology unit at Cochin Hospital, Paris, France. "In this Phase II study, adding BMS-790052 once daily to peginterferon alfa and ribavirin produced SVR rates and safety findings that warranted further development of BMS-790052."
Study Results
BMS-790052 plus pegIFNalfa/RBV achieved higher rates of SVR24 compared to pegIFNalfa/RBV alone across all BMS-790052 treatment groups [BMS-790052: 60 mg: 83% (n=10/12), 10 mg: 83% (10/12), 3 mg: 42% (5/12); control: 25% (3/12)].
Adverse events (AEs) leading to discontinuation with BMS-790052 plus pegINFalfa/RBV were comparable with treatment with pegIFNalfa/RBV plus placebo. One patient (8.3%) in each of the 3 mg and 10 mg groups and four patients (33.3%) in the 60 mg group discontinued due to AEs, compared with two patients (16.7%) in the control group. Reasons for discontinuation were a diverse set of AEs sometimes associated with the use of pegIFNalfa/RBV.
Serious adverse events (SAEs) and overall AEs were comparable across study arms. The addition of BMS-790052 to pegIFNalfa/RBV therapy did not result in any apparent incremental hematologic, hepatic or dermatologic adverse events. One patient (8.3%) in each of the BMS-790052 treatment groups experienced a SAE during therapy compared with zero patients in the control group. On-treatment Grade 3-4 AEs were: BMS-790052 60 mg: 33.0%, 10 mg: 25.0%, 3 mg: 8.3%; control: 41.7%. One patient (8.3%) in each of the BMS-790052 3 mg and 60 mg groups experienced hemoglobin <10 g/dL, compared with zero patients in the 10 mg and control groups. AEs occurring in at least four patients (33.3%) in any cohort were consistent across BMS-790052 treatment arms and the placebo arm, and included the following events of interest: anemia (bms-790052:60 mg)(10 mg:41.7%)(3 mg:25.0%)(control:41.7%), nausea (bms-790052:60 mg)(10 mg:33.3%)(3 mg:41.7%)(control:50.0%), vomiting (bms-790052 60 mg:33.3%)(10 mg:8.3%)(3 mg:16.7%)(control:0%), neutropenia (bms-790052:60 mg)(10 mg:33.3%)(3 mg:25.0%)(control:41.7%), and rash (bms-790052:60 mg)(10 mg:33.3%)(3 mg:33.3%)(control:25.0%).
Erythropoietin use was comparable across all study arms. Three patients (25.0%) in each of the BMS-790052 10 mg and 60 mg groups and one patient (8.3%) in the 3 mg group required erythropoietin, compared with two patients (16.7%) in the control group. The use of filgrastim (G-CSF) in the study groups was: BMS-790052 60 mg: 0%, 10 mg: 25.0%, 3 mg: 16.7%; control: 16.7%.
About the Study
This double-blind study randomized 48 treatment-naive HCV genotype 1-infected, non-cirrhotic patients 1:1:1:1 (n=12/arm) to receive one of three doses of BMS-790052 (3 mg, 10 mg, or 60 mg) or placebo once daily, in combination with peginterferon alfa-2a and ribavirin for 48 weeks. The primary endpoint of the study was the proportion of patients with extended rapid virologic response (eRVR), defined as undetectable viral load (HCV RNA < 10 IU/mL) at both Weeks 4 and 12. Primary endpoint data were previously reported at EASL 2010 in Vienna, Austria.
About BMS-790052
Discovered by Bristol-Myers Squibb through a genomics approach, BMS-790052 is the first NS5A replication complex inhibitor to be investigated in HCV clinical trials and is currently in Phase III development. BMS-790052 is part of a portfolio of investigational compounds that the company is developing for the treatment of hepatitis C.
About Hepatitis C
Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. An estimated 170 million people worldwide are infected with hepatitis C. Up to 90 percent of those infected with hepatitis C will not clear the virus and will become chronically infected. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to one quarter may progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a potentially curable disease.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews .
Bristol-Myers Squibb Forward Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that clinical trials of this compound will support a regulatory filing, or that the compound will receive regulatory approval or, if approved, that it will become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2010, in our Quarterly Reports on Form 10-Q, and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
SOURCE: Bristol-Myers Squibb Company
Bristol-Myers Squibb
Media:
Sonia Choi, 609-252-5132
sonia.choi@bms.com
or
Cristi Barnett, 609-252-6028
cristi.barnett@bms.com
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com
BMS-790052 Plus Peginterferon Alfa and Ribavirin Demonstrated up to 83% Sustained Virologic Response 24 Weeks Post-Treatment (SVR24) in Phase II Study of Genotype 1 Hepatitis C Patients
In this study,adverse event profile of regimen containing BMS-790052 was consistent with that of treatment with peginterferon alfa and ribavirin plus placebo
PRINCETON, N.J., Sep 17, 2011 (BUSINESS WIRE) -- --Company has initiated Phase III development program for BMS-790052
Bristol-Myers Squibb Company BMY -0.72% today announced results from a Phase II clinical trial of 48 treatment-naive genotype 1 hepatitis C infected patients in which treatment with BMS-790052, an NS5A replication complex inhibitor, in combination with peginterferon alfa and ribavirin (pegIFNalfa/RBV) maintained undetectable viral load at 24 weeks post-treatment (SVR24) in 83% (60 mg), 83% (10 mg) and 42% (3 mg) of patients, compared with 25% of patients in the pegIFNalfa/RBV control group after 48 weeks of combination therapy. In this study, serious adverse events were reported in one patient (8.3%) from each of the BMS-790052 treatment groups and in zero patients from the control group. The data were reported today at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Chicago. The investigational direct acting antiviral BMS-790052 is now in Phase III development.
"The hepatitis C treatment landscape is rapidly evolving and although there have been positive advances recently, there remains a need for additional therapies with a more favorable efficacy and safety profile," said Stanislas Pol, MD, PhD, Professor of Hepatology at Universite Paris V (Rene Descartes), Paris, France and head of the Hepatology unit at Cochin Hospital, Paris, France. "In this Phase II study, adding BMS-790052 once daily to peginterferon alfa and ribavirin produced SVR rates and safety findings that warranted further development of BMS-790052."
Study Results
BMS-790052 plus pegIFNalfa/RBV achieved higher rates of SVR24 compared to pegIFNalfa/RBV alone across all BMS-790052 treatment groups [BMS-790052: 60 mg: 83% (n=10/12), 10 mg: 83% (10/12), 3 mg: 42% (5/12); control: 25% (3/12)].
Adverse events (AEs) leading to discontinuation with BMS-790052 plus pegINFalfa/RBV were comparable with treatment with pegIFNalfa/RBV plus placebo. One patient (8.3%) in each of the 3 mg and 10 mg groups and four patients (33.3%) in the 60 mg group discontinued due to AEs, compared with two patients (16.7%) in the control group. Reasons for discontinuation were a diverse set of AEs sometimes associated with the use of pegIFNalfa/RBV.
Serious adverse events (SAEs) and overall AEs were comparable across study arms. The addition of BMS-790052 to pegIFNalfa/RBV therapy did not result in any apparent incremental hematologic, hepatic or dermatologic adverse events. One patient (8.3%) in each of the BMS-790052 treatment groups experienced a SAE during therapy compared with zero patients in the control group. On-treatment Grade 3-4 AEs were: BMS-790052 60 mg: 33.0%, 10 mg: 25.0%, 3 mg: 8.3%; control: 41.7%. One patient (8.3%) in each of the BMS-790052 3 mg and 60 mg groups experienced hemoglobin <10 g/dL, compared with zero patients in the 10 mg and control groups. AEs occurring in at least four patients (33.3%) in any cohort were consistent across BMS-790052 treatment arms and the placebo arm, and included the following events of interest: anemia (bms-790052:60 mg)(10 mg:41.7%)(3 mg:25.0%)(control:41.7%), nausea (bms-790052:60 mg)(10 mg:33.3%)(3 mg:41.7%)(control:50.0%), vomiting (bms-790052 60 mg:33.3%)(10 mg:8.3%)(3 mg:16.7%)(control:0%), neutropenia (bms-790052:60 mg)(10 mg:33.3%)(3 mg:25.0%)(control:41.7%), and rash (bms-790052:60 mg)(10 mg:33.3%)(3 mg:33.3%)(control:25.0%).
Erythropoietin use was comparable across all study arms. Three patients (25.0%) in each of the BMS-790052 10 mg and 60 mg groups and one patient (8.3%) in the 3 mg group required erythropoietin, compared with two patients (16.7%) in the control group. The use of filgrastim (G-CSF) in the study groups was: BMS-790052 60 mg: 0%, 10 mg: 25.0%, 3 mg: 16.7%; control: 16.7%.
About the Study
This double-blind study randomized 48 treatment-naive HCV genotype 1-infected, non-cirrhotic patients 1:1:1:1 (n=12/arm) to receive one of three doses of BMS-790052 (3 mg, 10 mg, or 60 mg) or placebo once daily, in combination with peginterferon alfa-2a and ribavirin for 48 weeks. The primary endpoint of the study was the proportion of patients with extended rapid virologic response (eRVR), defined as undetectable viral load (HCV RNA < 10 IU/mL) at both Weeks 4 and 12. Primary endpoint data were previously reported at EASL 2010 in Vienna, Austria.
About BMS-790052
Discovered by Bristol-Myers Squibb through a genomics approach, BMS-790052 is the first NS5A replication complex inhibitor to be investigated in HCV clinical trials and is currently in Phase III development. BMS-790052 is part of a portfolio of investigational compounds that the company is developing for the treatment of hepatitis C.
About Hepatitis C
Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. An estimated 170 million people worldwide are infected with hepatitis C. Up to 90 percent of those infected with hepatitis C will not clear the virus and will become chronically infected. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to one quarter may progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a potentially curable disease.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews .
Bristol-Myers Squibb Forward Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that clinical trials of this compound will support a regulatory filing, or that the compound will receive regulatory approval or, if approved, that it will become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2010, in our Quarterly Reports on Form 10-Q, and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
SOURCE: Bristol-Myers Squibb Company
Bristol-Myers Squibb
Media:
Sonia Choi, 609-252-5132
sonia.choi@bms.com
or
Cristi Barnett, 609-252-6028
cristi.barnett@bms.com
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com
Inhibitex starts dosing in Phase II trial looking at INX-189 in HCV genotype 2 & 3 subjects...
Inhibitex Commences Dosing of Phase 2 Clinical Trial of INX-189 in HCV Infected Genotype 2/3 Patients
Phase 1b Extension Trial in HCV-Infected Genotype 1 Patients to Evaluate Higher Doses of INX-189 Also Initiated
ATLANTA, Sep 19, 2011 (BUSINESS WIRE) -- Inhibitex, Inc. INHX +2.13% , announced today that it has recently commenced dosing in a 90-patient randomized, placebo controlled, treatment guided, Phase 2 clinical trial to evaluate the safety, tolerability and antiviral activity of INX-189 in combination with pegylated interferon and ribavirin in chronic HCV-infected genotype 2 and 3 treatment naive patients. The trial is designed to evaluate three once-daily doses of INX-189 (25 mg, 50 mg and 100 mg) administered in combination with pegylated interferon and ribavirin for 12 weeks, and also includes a control arm in which patients will receive placebo and standard of care treatment (a combination of pegylated interferon and ribavirin for 24 weeks). Each INX-189 combination treatment cohort in the trial will include 25 patients, and the control arm will include 15 patients.
Patients in the INX-189 containing treatment arms that achieve an extended rapid viral response, or eRVR, defined as having HCV RNA below the level of detection after 28 days and 12 weeks of dosing, will stop all therapy after 12 weeks. Those patients who do not achieve an eRVR will continue receiving pegylated interferon and ribavirin for 12 additional weeks.
The Company also announced the initiation of an additional clinical trial of INX-189 designed to evaluate higher doses of INX-189 administered as monotherapy or in combination with ribavirin for seven days. The first cohort in this expanded Phase 1b trial will receive 200 mg INX-189 once daily as monotherapy. Other planned cohorts include 100 mg INX-189 twice daily as monotherapy, 100 mg INX-189 once daily in combination with ribavirin, and possibly higher monotherapy doses of INX-189. Each treatment cohort in the trial will include 10 patients, eight of which will receive INX-189 and two of which will receive placebo.
About HCV and INX-189
Hepatitis C is a disease of the liver caused by the hepatitis C virus (HCV). It is estimated that over 4 million Americans and 170 million individuals worldwide are infected with HCV, the majority of which represent chronic infections that can cause liver disease, cirrhosis and cancer, and is the leading cause of liver transplants in the United States.
Inhibitex is developing a series of proprietary nucleotide inhibitors that target the RNA-dependent RNA polymerase (NS5b) of HCV. INX-189 is a protide of a 2'-C-methyl guanosine analogue. The Company believes that preclinical and clinical studies of INX-189 completed to-date support its potential as a potent, once-daily, low dose oral therapy amenable to combination with other antivirals for the treatment of patients with all known genotypes of HCV.
About Inhibitex
Inhibitex, Inc. is a biopharmaceutical company focused on developing products to prevent and treat serious infectious diseases. The Company's clinical-stage pipeline currently includes two Phase 2 development programs; INX-189, a nucleotide polymerase inhibitor in development for the treatment of chronic hepatitis C infections and FV-100, a nucleoside analogue in development for the treatment of shingles-associated pain. The Company also has other HCV nucleotide polymerase inhibitors in preclinical development and has licensed the use of its proprietary MSCRAMM(R) protein platform to Pfizer for the development of a staphylococcal vaccine, which is currently being evaluated in a Phase 1/2 clinical trial. For additional information about the Company, please visit www.inhibitex.com .
Safe Harbor Statement
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than historical facts included in this press release, including statements regarding the number of patients the Company expects to enroll in the ongoing Phase 2 trial and the planned cohorts, and possibly including higher monotherapy doses of INX-189, in the ongoing supplementary Phase 1b trial, and the Company's belief that preclinical and clinical studies of INX-189 completed to-date support its potential as a potent, once-daily, low dose oral therapy amenable to combination with other antivirals for the treatment of patients with all known genotypes of HCV, are forward looking statements. These intentions, expectations, or results may not be achieved in the future and various important factors could cause actual results or events to differ materially from the forward-looking statements that the Company makes, including the risk of the Company, the FDA, a data safety monitoring board, an institutional review board (IRB), delaying, limiting, suspending or terminating the clinical development of INX-189 at any time for a lack of safety, tolerability, biologic activity or efficacy, commercial viability, regulatory issues, or any other reason and other cautionary statements contained elsewhere herein and in its Annual Report on Form 10-K for the year ended December 31, 2010 and its Quarterly Reports on Form 10-Q for the quarters ended March 31 and June 30, 2011. Given these uncertainties, you should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release.
There may be events in the future that the Company is unable to predict accurately, or over which it has no control. The Company's business, financial condition, results of operations and prospects may change. The Company may not update these forward-looking statements, even though its situation may change in the future, unless it has obligations under the Federal securities laws to update and disclose material developments related to previously disclosed information. The Company qualifies all of the information contained in this press release, and particularly its forward-looking statements, by these cautionary statements.
Inhibitex(R) and MSCRAMM(R) are registered trademarks of Inhibitex, Inc.
SOURCE: Inhibitex, Inc.
Inhibitex
Russell H. Plumb, 678-746-1136
Chief Executive Officer
rplumb@inhibitex.com
or
The Trout Group
Lee M. Stern, 646-378-2922
CFA
lstern@troutgroup.com
Phase 1b Extension Trial in HCV-Infected Genotype 1 Patients to Evaluate Higher Doses of INX-189 Also Initiated
ATLANTA, Sep 19, 2011 (BUSINESS WIRE) -- Inhibitex, Inc. INHX +2.13% , announced today that it has recently commenced dosing in a 90-patient randomized, placebo controlled, treatment guided, Phase 2 clinical trial to evaluate the safety, tolerability and antiviral activity of INX-189 in combination with pegylated interferon and ribavirin in chronic HCV-infected genotype 2 and 3 treatment naive patients. The trial is designed to evaluate three once-daily doses of INX-189 (25 mg, 50 mg and 100 mg) administered in combination with pegylated interferon and ribavirin for 12 weeks, and also includes a control arm in which patients will receive placebo and standard of care treatment (a combination of pegylated interferon and ribavirin for 24 weeks). Each INX-189 combination treatment cohort in the trial will include 25 patients, and the control arm will include 15 patients.
Patients in the INX-189 containing treatment arms that achieve an extended rapid viral response, or eRVR, defined as having HCV RNA below the level of detection after 28 days and 12 weeks of dosing, will stop all therapy after 12 weeks. Those patients who do not achieve an eRVR will continue receiving pegylated interferon and ribavirin for 12 additional weeks.
The Company also announced the initiation of an additional clinical trial of INX-189 designed to evaluate higher doses of INX-189 administered as monotherapy or in combination with ribavirin for seven days. The first cohort in this expanded Phase 1b trial will receive 200 mg INX-189 once daily as monotherapy. Other planned cohorts include 100 mg INX-189 twice daily as monotherapy, 100 mg INX-189 once daily in combination with ribavirin, and possibly higher monotherapy doses of INX-189. Each treatment cohort in the trial will include 10 patients, eight of which will receive INX-189 and two of which will receive placebo.
About HCV and INX-189
Hepatitis C is a disease of the liver caused by the hepatitis C virus (HCV). It is estimated that over 4 million Americans and 170 million individuals worldwide are infected with HCV, the majority of which represent chronic infections that can cause liver disease, cirrhosis and cancer, and is the leading cause of liver transplants in the United States.
Inhibitex is developing a series of proprietary nucleotide inhibitors that target the RNA-dependent RNA polymerase (NS5b) of HCV. INX-189 is a protide of a 2'-C-methyl guanosine analogue. The Company believes that preclinical and clinical studies of INX-189 completed to-date support its potential as a potent, once-daily, low dose oral therapy amenable to combination with other antivirals for the treatment of patients with all known genotypes of HCV.
About Inhibitex
Inhibitex, Inc. is a biopharmaceutical company focused on developing products to prevent and treat serious infectious diseases. The Company's clinical-stage pipeline currently includes two Phase 2 development programs; INX-189, a nucleotide polymerase inhibitor in development for the treatment of chronic hepatitis C infections and FV-100, a nucleoside analogue in development for the treatment of shingles-associated pain. The Company also has other HCV nucleotide polymerase inhibitors in preclinical development and has licensed the use of its proprietary MSCRAMM(R) protein platform to Pfizer for the development of a staphylococcal vaccine, which is currently being evaluated in a Phase 1/2 clinical trial. For additional information about the Company, please visit www.inhibitex.com .
Safe Harbor Statement
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than historical facts included in this press release, including statements regarding the number of patients the Company expects to enroll in the ongoing Phase 2 trial and the planned cohorts, and possibly including higher monotherapy doses of INX-189, in the ongoing supplementary Phase 1b trial, and the Company's belief that preclinical and clinical studies of INX-189 completed to-date support its potential as a potent, once-daily, low dose oral therapy amenable to combination with other antivirals for the treatment of patients with all known genotypes of HCV, are forward looking statements. These intentions, expectations, or results may not be achieved in the future and various important factors could cause actual results or events to differ materially from the forward-looking statements that the Company makes, including the risk of the Company, the FDA, a data safety monitoring board, an institutional review board (IRB), delaying, limiting, suspending or terminating the clinical development of INX-189 at any time for a lack of safety, tolerability, biologic activity or efficacy, commercial viability, regulatory issues, or any other reason and other cautionary statements contained elsewhere herein and in its Annual Report on Form 10-K for the year ended December 31, 2010 and its Quarterly Reports on Form 10-Q for the quarters ended March 31 and June 30, 2011. Given these uncertainties, you should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release.
There may be events in the future that the Company is unable to predict accurately, or over which it has no control. The Company's business, financial condition, results of operations and prospects may change. The Company may not update these forward-looking statements, even though its situation may change in the future, unless it has obligations under the Federal securities laws to update and disclose material developments related to previously disclosed information. The Company qualifies all of the information contained in this press release, and particularly its forward-looking statements, by these cautionary statements.
Inhibitex(R) and MSCRAMM(R) are registered trademarks of Inhibitex, Inc.
SOURCE: Inhibitex, Inc.
Inhibitex
Russell H. Plumb, 678-746-1136
Chief Executive Officer
rplumb@inhibitex.com
or
The Trout Group
Lee M. Stern, 646-378-2922
CFA
lstern@troutgroup.com
Wednesday, September 14, 2011
Telaprevir Phase 3 trial "ILLUMINATE" published in the New England Journal of Medicine...
Vertex press release touting the publication of their ILLUMINATE study being published in the September 15th New England Journal of Medicine... no small feat, this will be the 3rd Vertex-initaited Telaprevir trial published in NEJM. ILLUMINATE was in genotype 1, treatment naive subjects and looked at 24 weeks (TVR + P/R for 12 weeks, then 12 weeks of P/R) vs 48 weeks (TVR + P/R for 12 weeks, then 36 weeks of P/R). The final results, which were measured in subjects that had undetectable virus at week for and week 12 and therefore eligible to remain on therapy :
• 92% SVR (149/162) for people who received the 24-week regimen
• 88% SVR (140/159) for people who received the 48-week regimen
According to this study, adding an additional 24 weeks to TVR + P/R had no benefit.
The more interesting aspect to this press release is the emphasis on 24 weeks of therapy, a not-so-subtle jab perhaps to Telaprevir's competition, Boceprevir which requires a more complex dosing regimen for a longer duration of therapy.
A compelling question remains, and hopefully will be addressed in the full study - what were the reasons attributable to the 35% (or 188 of the 540 subjects) of these genotype 1 treatment-naïve patients that had detectable virus at week 4 and week 12? 188 patients that were Telaprevir non-responders is not insignificant.
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the New England Journal of Medicine (NEJM) published data from a Phase 3 study of INCIVEK (telaprevir) tablets in people with genotype 1 chronic hepatitis C who were new to treatment. In ILLUMINATE, INCIVEK (in-SEE-veck) was given for the first 12 weeks in combination with pegylated-interferon and ribavirin. Nearly two-thirds of patients responded early to INCIVEK combination treatment (measured by having undetectable hepatitis C virus at weeks 4 and 12 of treatment) and were randomly assigned to receive an additional 12 weeks or 36 weeks of treatment with pegylated-interferon and ribavirin alone. Similarly high rates of sustained viral response (SVR, or viral cure) were achieved by people in both treatment groups. Rash and anemia were the most common side effects reported with INCIVEK in this study and each led to treatment discontinuation of all medicines in about 1 percent of people during the INCIVEK treatment phase. Data from ILLUMINATE are published in the September 15, 2011 issue of NEJM.
"These data are important because they showed that patients who respond early to INCIVEK combination treatment have a high likelihood of achieving a viral cure with 24 weeks of therapy," said Kenneth Sherman, M.D., Ph.D., Professor of Medicine at the University of Cincinnati College of Medicine, Director of the Division of Digestive Diseases for UC Health and principal investigator for the study. "With INCIVEK, we know by week four how patients are initially responding and, for people who have not been treated before, we know by week 12 what their chances are of completing all therapy in 24 weeks. I believe these are important motivators for patients to start and stay on treatment."
"Nearly two-thirds of people in this study had an early response to INCIVEK combination treatment and were eligible to stop all therapy at week 24," said Peter Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of Global Research and Development at Vertex. "Cutting treatment time in half eliminates 24 weeks of pegylated-interferon and ribavirin and represents a major advance in how hepatitis C is treated."
Results From ILLUMINATE
ILLUMINATE was an open-label, randomized Phase 3 study that evaluated INCIVEK in combination with Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin) in 540 people with genotype 1 chronic hepatitis C who were new to treatment. In this study, 65 percent (352/540) of people had undetectable hepatitis C virus at weeks 4 and 12. To assess whether there was any benefit to extending treatment in this group, eligible patients who remained on treatment were randomized at week 20 to receive a total of either 24 weeks or 48 weeks of treatment. Patients whose hepatitis C virus was detectable at weeks 4 or 12 were assigned to receive 48 weeks of total treatment.
The primary endpoint of the study was the proportion of people who achieved SVR in the randomized treatment groups (those who had undetectable hepatitis C virus at weeks 4 and 12), evaluated by a non-inferiority analysis.
The data published in NEJM showed that the rates of viral cure were similar between the two groups of people whose hepatitis C virus was undetectable at weeks 4 and 12:
• 92% SVR (149/162) for people who received the 24-week regimen
• 88% SVR (140/159) for people who received the 48-week regimen
Rash and anemia are the most serious side effects associated with INCIVEK. The most common side effects reported with INCIVEK combination treatment include fatigue, itching, nausea, diarrhea, vomiting, anal or rectal problems and taste changes.
INCIVEK was approved by U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for the treatment of genotype 1 chronic hepatitis C in adults with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). The approvals were based on data from three Phase 3 studies: ADVANCE, REALIZE and ILLUMINATE. Data from the ADVANCE and REALIZE studies were published in the June 23, 2011 issue of NEJM. More than 2,800 people received INCIVEK combination treatment as part of Phase 2 and Phase 3 clinical studies.
About INCIVEK
INCIVEK is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK (750 mg) is given as two 375 mg tablets three times daily for 12 weeks in combination with pegylated-interferon and ribavirin. Each monthly package of INCIVEK contains four weekly boxes that include daily blister strips to help patients keep track of their doses. After the first 12 weeks, all patients stop receiving INCIVEK and continue treatment with pegylated-interferon and ribavirin alone for an additional 12 weeks or 36 weeks of treatment. With INCIVEK combination therapy, more than 60 percent of people treated for the first time, as well as those who relapsed after previous therapy, are expected to complete all treatment in 24 weeks. All other patients receive a total of 48 weeks of treatment.
Vertex developed telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it will be marketed under the brand name INCIVEK (in-SEE-veck). Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Telaprevir, which will be known as INCIVO in Europe, received accelerated review by the Committee for Medicinal Products for Human Use (CHMP), which issued a positive opinion in July 2011. Telaprevir was approved in Switzerland in September 2011. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. Telaprevir has been recommended for approval at the Second Committee on Drugs at the Department on Drugs in the Pharmaceutical Affairs and Food Sanitation Council (PAFSC) in Japan.
IMPORTANT SAFETY INFORMATION
Indication
INCIVEK? (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.
Important Safety Information
INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant.
INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.
INCIVEK can cause serious side effects including rash and anemia. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.
Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com.
INCIVEK? is a trademark of Vertex Pharmaceuticals Incorporated.
PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1
Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 However, approximately 60 percent of people do not achieve SVR,3,4,5 or viral cure,6 after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8
More than 170 million people worldwide are chronically infected with hepatitis C.6 In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.9 Hepatitis C is four times more prevalent in the United States compared to HIV.9 The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.10 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.11,12 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.9
Additional resources for media are available at: http://investors.vrtx.com/press.cfm.
About Vertex
Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada.
(VRTX - GEN)
1 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed March 21, 2011.
2 Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.
3 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
4 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
5 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
6 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
7 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
8 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
9 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed March 21, 2011.
10 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. Available at: http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. Accessed March 21, 2011. This report was commissioned by Vertex Pharmaceuticals, Inc.
11 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
12 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.
Photos/Multimedia Gallery Available: http://www.businesswire.com/cgi-bin/mmg.cgi?eid=50004789&lang=en
Vertex Contacts:
Media:
Dawn Kalmar, 617-444-6992
or
Amy Pasqua, 617-444-6992
mediainfo@vrtx.com
or
Patient Inquiries: 1-855- 837-8394
or
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
or
Matthew Osborne, 617-444-6057
• 92% SVR (149/162) for people who received the 24-week regimen
• 88% SVR (140/159) for people who received the 48-week regimen
According to this study, adding an additional 24 weeks to TVR + P/R had no benefit.
The more interesting aspect to this press release is the emphasis on 24 weeks of therapy, a not-so-subtle jab perhaps to Telaprevir's competition, Boceprevir which requires a more complex dosing regimen for a longer duration of therapy.
A compelling question remains, and hopefully will be addressed in the full study - what were the reasons attributable to the 35% (or 188 of the 540 subjects) of these genotype 1 treatment-naïve patients that had detectable virus at week 4 and week 12? 188 patients that were Telaprevir non-responders is not insignificant.
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the New England Journal of Medicine (NEJM) published data from a Phase 3 study of INCIVEK (telaprevir) tablets in people with genotype 1 chronic hepatitis C who were new to treatment. In ILLUMINATE, INCIVEK (in-SEE-veck) was given for the first 12 weeks in combination with pegylated-interferon and ribavirin. Nearly two-thirds of patients responded early to INCIVEK combination treatment (measured by having undetectable hepatitis C virus at weeks 4 and 12 of treatment) and were randomly assigned to receive an additional 12 weeks or 36 weeks of treatment with pegylated-interferon and ribavirin alone. Similarly high rates of sustained viral response (SVR, or viral cure) were achieved by people in both treatment groups. Rash and anemia were the most common side effects reported with INCIVEK in this study and each led to treatment discontinuation of all medicines in about 1 percent of people during the INCIVEK treatment phase. Data from ILLUMINATE are published in the September 15, 2011 issue of NEJM.
"These data are important because they showed that patients who respond early to INCIVEK combination treatment have a high likelihood of achieving a viral cure with 24 weeks of therapy," said Kenneth Sherman, M.D., Ph.D., Professor of Medicine at the University of Cincinnati College of Medicine, Director of the Division of Digestive Diseases for UC Health and principal investigator for the study. "With INCIVEK, we know by week four how patients are initially responding and, for people who have not been treated before, we know by week 12 what their chances are of completing all therapy in 24 weeks. I believe these are important motivators for patients to start and stay on treatment."
"Nearly two-thirds of people in this study had an early response to INCIVEK combination treatment and were eligible to stop all therapy at week 24," said Peter Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of Global Research and Development at Vertex. "Cutting treatment time in half eliminates 24 weeks of pegylated-interferon and ribavirin and represents a major advance in how hepatitis C is treated."
Results From ILLUMINATE
ILLUMINATE was an open-label, randomized Phase 3 study that evaluated INCIVEK in combination with Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin) in 540 people with genotype 1 chronic hepatitis C who were new to treatment. In this study, 65 percent (352/540) of people had undetectable hepatitis C virus at weeks 4 and 12. To assess whether there was any benefit to extending treatment in this group, eligible patients who remained on treatment were randomized at week 20 to receive a total of either 24 weeks or 48 weeks of treatment. Patients whose hepatitis C virus was detectable at weeks 4 or 12 were assigned to receive 48 weeks of total treatment.
The primary endpoint of the study was the proportion of people who achieved SVR in the randomized treatment groups (those who had undetectable hepatitis C virus at weeks 4 and 12), evaluated by a non-inferiority analysis.
The data published in NEJM showed that the rates of viral cure were similar between the two groups of people whose hepatitis C virus was undetectable at weeks 4 and 12:
• 92% SVR (149/162) for people who received the 24-week regimen
• 88% SVR (140/159) for people who received the 48-week regimen
Rash and anemia are the most serious side effects associated with INCIVEK. The most common side effects reported with INCIVEK combination treatment include fatigue, itching, nausea, diarrhea, vomiting, anal or rectal problems and taste changes.
INCIVEK was approved by U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for the treatment of genotype 1 chronic hepatitis C in adults with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). The approvals were based on data from three Phase 3 studies: ADVANCE, REALIZE and ILLUMINATE. Data from the ADVANCE and REALIZE studies were published in the June 23, 2011 issue of NEJM. More than 2,800 people received INCIVEK combination treatment as part of Phase 2 and Phase 3 clinical studies.
About INCIVEK
INCIVEK is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK (750 mg) is given as two 375 mg tablets three times daily for 12 weeks in combination with pegylated-interferon and ribavirin. Each monthly package of INCIVEK contains four weekly boxes that include daily blister strips to help patients keep track of their doses. After the first 12 weeks, all patients stop receiving INCIVEK and continue treatment with pegylated-interferon and ribavirin alone for an additional 12 weeks or 36 weeks of treatment. With INCIVEK combination therapy, more than 60 percent of people treated for the first time, as well as those who relapsed after previous therapy, are expected to complete all treatment in 24 weeks. All other patients receive a total of 48 weeks of treatment.
Vertex developed telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it will be marketed under the brand name INCIVEK (in-SEE-veck). Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Telaprevir, which will be known as INCIVO in Europe, received accelerated review by the Committee for Medicinal Products for Human Use (CHMP), which issued a positive opinion in July 2011. Telaprevir was approved in Switzerland in September 2011. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. Telaprevir has been recommended for approval at the Second Committee on Drugs at the Department on Drugs in the Pharmaceutical Affairs and Food Sanitation Council (PAFSC) in Japan.
IMPORTANT SAFETY INFORMATION
Indication
INCIVEK? (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.
Important Safety Information
INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant.
INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.
INCIVEK can cause serious side effects including rash and anemia. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.
Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com.
INCIVEK? is a trademark of Vertex Pharmaceuticals Incorporated.
PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1
Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 However, approximately 60 percent of people do not achieve SVR,3,4,5 or viral cure,6 after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8
More than 170 million people worldwide are chronically infected with hepatitis C.6 In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.9 Hepatitis C is four times more prevalent in the United States compared to HIV.9 The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.10 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.11,12 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.9
Additional resources for media are available at: http://investors.vrtx.com/press.cfm.
About Vertex
Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada.
(VRTX - GEN)
1 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed March 21, 2011.
2 Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.
3 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
4 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
5 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
6 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
7 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
8 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
9 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed March 21, 2011.
10 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. Available at: http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. Accessed March 21, 2011. This report was commissioned by Vertex Pharmaceuticals, Inc.
11 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
12 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.
Photos/Multimedia Gallery Available: http://www.businesswire.com/cgi-bin/mmg.cgi?eid=50004789&lang=en
Vertex Contacts:
Media:
Dawn Kalmar, 617-444-6992
or
Amy Pasqua, 617-444-6992
mediainfo@vrtx.com
or
Patient Inquiries: 1-855- 837-8394
or
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
or
Matthew Osborne, 617-444-6057
Friday, September 9, 2011
IL28B gene of chromosome 19 as a predictor of SVR in HCV antiviral therapy...
From the Irish Medical Times - we've seen before many times the correlation between SVR and variations in the interleukin 28B (IL28B) gene of chromosome 19, but this serves as a reminder of how powerful a predictor it can be. LabCorp offers a commercial assay available to HCV providers here in the States
Genetic markers promising as guide to HCV therapy
September 9, 2011 By Mary Anne Kenny
Two genes first described in 2009 and 2010 have considerable promise as predictors of patients’ responses to pegylated interferon and ribavirin, Australian hepatologists have claimed.
Dr Jacinta Holmes and colleagues from St Vincent’s Hospital in Melbourne said variations in the interleukin 28B (IL28B) gene of chromosome 19 were known to be strongly associated with treatment outcome in patients with hepatitis C virus genotype 1 (HCV-1) receiving the two medications.
“Patients carrying the ‘good response’ variant had two- to three-fold higher rates of sustained virological response (SVR),” they said.
Differences in the frequency of the alleles in different racial groups also explained much of the known racial disparity in response rates.
IL28B polymorphism had also been associated with spontaneous clearance of acute HCV infection.
Two functional variants of the second gene, located on chromosome 20 and coding for inosine triphosphatase, had been found to protect against ribavirin-induced haemolytic anaemia. This side effect was dose-limiting in up to 15 per cent of patients enrolled in clinical trials.
“These exciting genetic discoveries are changing how we think about HCV pathogenesis, patient evaluation and current treatment paradigms,” they said. More research was needed, however, before the tests were likely to be incorporated into routine practice.
Although pegylated interferon and ribavirin were the current standard of care for HCV, the success rate was disappointing, as only about 55 per cent of patients achieved an SVR. In these circumstances the cost and side effects of treatment were an important consideration, the authors said.
“It would be clinically useful to be able to accurately predict at baseline which patients are most likely to achieve SVR, both to prioritise their treatment and spare unnecessary morbidity for those with a very low probability of clearance,” they concluded.
Clinical Liver Disease
2011; 15: 497-513.
Genetic markers promising as guide to HCV therapy
September 9, 2011 By Mary Anne Kenny
Two genes first described in 2009 and 2010 have considerable promise as predictors of patients’ responses to pegylated interferon and ribavirin, Australian hepatologists have claimed.
Dr Jacinta Holmes and colleagues from St Vincent’s Hospital in Melbourne said variations in the interleukin 28B (IL28B) gene of chromosome 19 were known to be strongly associated with treatment outcome in patients with hepatitis C virus genotype 1 (HCV-1) receiving the two medications.
“Patients carrying the ‘good response’ variant had two- to three-fold higher rates of sustained virological response (SVR),” they said.
Differences in the frequency of the alleles in different racial groups also explained much of the known racial disparity in response rates.
IL28B polymorphism had also been associated with spontaneous clearance of acute HCV infection.
Two functional variants of the second gene, located on chromosome 20 and coding for inosine triphosphatase, had been found to protect against ribavirin-induced haemolytic anaemia. This side effect was dose-limiting in up to 15 per cent of patients enrolled in clinical trials.
“These exciting genetic discoveries are changing how we think about HCV pathogenesis, patient evaluation and current treatment paradigms,” they said. More research was needed, however, before the tests were likely to be incorporated into routine practice.
Although pegylated interferon and ribavirin were the current standard of care for HCV, the success rate was disappointing, as only about 55 per cent of patients achieved an SVR. In these circumstances the cost and side effects of treatment were an important consideration, the authors said.
“It would be clinically useful to be able to accurately predict at baseline which patients are most likely to achieve SVR, both to prioritise their treatment and spare unnecessary morbidity for those with a very low probability of clearance,” they concluded.
Clinical Liver Disease
2011; 15: 497-513.
Thursday, September 8, 2011
Santaris Pharma A/S provides update on Miravirsen for treatment of HCV...
Santaris Pharma A/S gives a preview update on miravirsen for treatment of HCV that will be presented at the 7th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) held September 8-10 in Copenhagen, Denmark. Miravirsen is the first microRNA-targeted drug inhibiting miR-122 to make it to clinic (it's currently in phase II trials) and to specifically target HCV. Miravirsen is the result of Santaris Pharma A/S propritary Locked Nucleic Acid Technology (LNA)drug platform, which has the potential to deliver drugs 'naked' without the complex delivery systems of RNA-based drugs. LNA-based compounds have the potential to inhibit entire microRNA families and is a new approach that opens up possibilities of successfully treating complex diseases such as cancer, viral infections, cardiovascular and muscle diseases
Santaris Pharma A/S Showcases microRNA and mRNA Research Advancements Utilizing its Proprietary Locked Nucleic Acid Technology at Oligonucleotide Therapeutics Society Meeting
HOERSHOLM, Denmark and SAN DIEGO, September 7, 2011 /PRNewswire/ --
Santaris Pharma A/S provides update on the development of miravirsen, a microRNA-targeted drug inhibiting miR-122, which is currently in Phase 2 clinical trials to treat patients infected with the Hepatitis C virus (HCV)
Scientists at Santaris Pharma A/S demonstrate specificity of "tiny" 8-mer LNA-based compounds, which have shown to successfully inhibit entire microRNA families providing potential new approach for treating cancer, viral infections, cardiovascular and muscle diseases
Data presented by scientists at Santaris Pharma A/S demonstrate successful "naked" delivery uptake of LNA-based compounds, a key advantage over other RNA-based technologies that require complex delivery vehicles
Versatility of the LNA Drug Platform allows Santaris Pharma A/S to develop both microRNA and mRNA-targeted drugs with excellent specificity and increased affinity to drug target, providing improved potency and favorable tissue-penetrating properties
Santaris Pharma A/S, a clinical-stage biopharmaceutical company focused on the research and development of mRNA and microRNA targeted therapies, today announced advancements from the company's RNA-targeted research programs utilizing its proprietary Locked Nucleic Acid (LNA) Drug Platform. In addition to a presentation on the Company's microRNA-targeted drug miravirsen, a total of six abstracts/posters are being showcased at the 7th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) held September 8-10 in Copenhagen, Denmark.
The LNA Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combines the Company's proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver potent single-stranded LNA-based drug candidates that can selectively inhibit mRNA and microRNA targets for a range of diseases including metabolic disorders, infectious and inflammatory diseases, cancer and rare genetic disorders.
"Santaris Pharma A/S is pleased to have the OTS hold its annual meeting here in Denmark this year as it recognizes the groundbreaking RNA-targeted research and development being conducted in Denmark from companies such as Santaris Pharma A/S as well as public institutions and research centers," said Henrik Oerum, Ph.D., Vice President and Chief Scientific Officer of Santaris Pharma A/S.
"Santaris Pharma A/S is excited to showcase its microRNA and mRNA-targeted research advancements utilizing its proprietary Locked Nucleic Acid Drug Platform," Dr. Oerum added. "The Company is providing an update on the progress of its lead microRNA-targeted drug candidate, miravirsen, for the treatment of Hepatitis C; presenting data on the use of Santaris Pharma A/S proprietary 'tiny' LNA-based drugs to inhibit entire microRNA-targeted families and highlighting data demonstrating 'naked' delivery uptake of LNA-based drugs, a key advantage over other RNA based technologies. This collection of data attests to the versatility of the LNA Drug Platform and clearly supports Santaris Pharma A/S leadership position in discovering and developing RNA-targeted medicines."
In a talk titled, "Targeting miRNA-122 for the Treatment of HCV," Dr. Oerum will provide an update on the development of miravirsen, the first microRNA-targeted drug to enter clinical trials, which is now in Phase 2 studies to assess the safety and tolerability of the drug in treatment-naïve patients infected with HCV. Data from Phase 1 clinical studies with miravirsen in healthy volunteers show that the drug is well tolerated.
Previously published data in Science demonstrated that miravirsen successfully inhibited miR-122 and dramatically reduced Hepatitis C virus in the liver and in the bloodstream in chimpanzees chronically infected with the Hepatitis C virus(1). Because of its unique mechanism of action and tolerability profile, miravirsen has the potential to be an effective treatment option for patients with HCV.
In addition, scientists at Santaris Pharma A/S will present data using proprietary bioinformatics techniques to demonstrate the specificity of "tiny" 8-mer LNA-based compounds, which have shown to successfully inhibit entire microRNA families providing potential new approach for treating a range of diseases including cancer, viral infections, cardiovascular and muscle diseases. Recent data published in Nature Genetics showed that the high affinity and target specificity of tiny LNA-based compounds enabled functional inhibition of entire microRNA families in a range of tissues without off-target effects(2).
MicroRNAs have emerged as an important class of small regulatory RNAs encoded in the genome. They act to control the expression of sets of genes and entire pathways and are thus thought of as master regulators of gene expression associated with many diseases. Because they dictate the expression of fundamental regulatory pathways, microRNAs represent potential drug targets in the treatment of many disease processes.
Santaris Pharma A/S also will present data demonstrating successful "naked" delivery uptake of LNA-based compounds, an advantage over other RNA-based technologies that require complex delivery vehicles. Data showed that LNA-based compounds readily enter cells in an active form allowing in vitro prediction of potent therapeutically active compounds as well as in vivo distribution to manifold cell types and tissues. Without the need for using complex delivery vehicles, the versatility of the LNA Drug Platform is the key for scientists to develop both microRNA and mRNA-targeted drugs with excellent specificity and increased affinity to drug target, providing improved potency and favorable tissue-penetrating properties.
The Santaris Pharma A/S LNA Drug Platform is the only RNA technology with both mRNA and microRNA targeted drugs in clinical trials, demonstrating the broad utility of the proprietary platform. In September 2010, Santaris Pharma A/S successfully advanced miravirsen, a lead microRNA drug candidate targeting miR-122, into Phase 2 studies for the treatment of patients infected with the Hepatitis C virus. In addition, Santaris Pharma A/S also advanced two mRNA-targeted drugs, SPC5001 targeting PCSK9 and SPC4955 targeting apoB, for the treatment of high cholesterol into Phase 1 in May 2011.
With its partners, Santaris Pharma A/S has a robust product pipeline consisting of mRNA and microRNA drug discovery and development collaborations. These include partnerships with Pfizer, Inc. (delivery of lead candidates against up to 20 targets), miRagen Therapeutics (cardiovascular diseases), Shire plc (rare genetic disorders), GlaxoSmithKline (four viral disease drug candidates) and Enzon Pharmaceuticals (eight cancer targets successfully delivered - three are now in Phase 1 clinical studies).
About Locked Nucleic Acid (LNA) Drug Platform
The LNA Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combines the Company's proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver LNA-based drug candidates against RNA targets, both mRNA and microRNA, for a range of diseases including cardiometabolic disorders, infectious and inflammatory diseases, cancer and rare genetic disorders. LNA-based drugs are a promising new class of therapeutics that are enabling scientists to develop drug candidates to target pathways previously considered inaccessible. The LNA Drug Platform overcomes the limitations of earlier antisense and siRNA technologies to deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The unique combination of small size and very high affinity allows this new class of drugs candidates to potently and specifically inhibit RNA targets in many different tissues without the need for complex delivery vehicles. The most important features of LNA-based drugs include excellent specificity providing optimal targeting; increased affinity to targets providing improved potency; and favorable pharmacokinetic and tissue-penetrating properties that allow systemic delivery of these drugs without complex and potentially troublesome delivery vehicles.
About Santaris Pharma A/S
Santaris Pharma A/S is a privately held clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies. The Locked Nucleic Acid (LNA) Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combine the Company's proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The Company's research and development activities focus on infectious diseases and cardiometabolic disorders, while partnerships with major pharmaceutical companies include a range of therapeutic areas including cancer, cardiovascular disease, infectious and inflammatory diseases, and rare genetic disorders. The Company has strategic partnerships with miRagen Therapeutics, Shire plc, Pfizer, GlaxoSmithKline, and Enzon Pharmaceuticals. As part of its broad patent estate, the Company holds exclusive worldwide rights to all therapeutic uses of LNA. Santaris Pharma A/S, founded in 2003, is headquartered in Denmark with operations in the United States. Please visit http://www.santaris.com for more information.
(1) Lanford et al, Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327 (5962): 198-201
(2) Obad, et al. Silencing of microRNA families by seed-targeting tiny LNAs. Nature Genetics 10.1038/ng.786.
Santaris Pharma A/S Showcases microRNA and mRNA Research Advancements Utilizing its Proprietary Locked Nucleic Acid Technology at Oligonucleotide Therapeutics Society Meeting
HOERSHOLM, Denmark and SAN DIEGO, September 7, 2011 /PRNewswire/ --
Santaris Pharma A/S provides update on the development of miravirsen, a microRNA-targeted drug inhibiting miR-122, which is currently in Phase 2 clinical trials to treat patients infected with the Hepatitis C virus (HCV)
Scientists at Santaris Pharma A/S demonstrate specificity of "tiny" 8-mer LNA-based compounds, which have shown to successfully inhibit entire microRNA families providing potential new approach for treating cancer, viral infections, cardiovascular and muscle diseases
Data presented by scientists at Santaris Pharma A/S demonstrate successful "naked" delivery uptake of LNA-based compounds, a key advantage over other RNA-based technologies that require complex delivery vehicles
Versatility of the LNA Drug Platform allows Santaris Pharma A/S to develop both microRNA and mRNA-targeted drugs with excellent specificity and increased affinity to drug target, providing improved potency and favorable tissue-penetrating properties
Santaris Pharma A/S, a clinical-stage biopharmaceutical company focused on the research and development of mRNA and microRNA targeted therapies, today announced advancements from the company's RNA-targeted research programs utilizing its proprietary Locked Nucleic Acid (LNA) Drug Platform. In addition to a presentation on the Company's microRNA-targeted drug miravirsen, a total of six abstracts/posters are being showcased at the 7th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) held September 8-10 in Copenhagen, Denmark.
The LNA Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combines the Company's proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver potent single-stranded LNA-based drug candidates that can selectively inhibit mRNA and microRNA targets for a range of diseases including metabolic disorders, infectious and inflammatory diseases, cancer and rare genetic disorders.
"Santaris Pharma A/S is pleased to have the OTS hold its annual meeting here in Denmark this year as it recognizes the groundbreaking RNA-targeted research and development being conducted in Denmark from companies such as Santaris Pharma A/S as well as public institutions and research centers," said Henrik Oerum, Ph.D., Vice President and Chief Scientific Officer of Santaris Pharma A/S.
"Santaris Pharma A/S is excited to showcase its microRNA and mRNA-targeted research advancements utilizing its proprietary Locked Nucleic Acid Drug Platform," Dr. Oerum added. "The Company is providing an update on the progress of its lead microRNA-targeted drug candidate, miravirsen, for the treatment of Hepatitis C; presenting data on the use of Santaris Pharma A/S proprietary 'tiny' LNA-based drugs to inhibit entire microRNA-targeted families and highlighting data demonstrating 'naked' delivery uptake of LNA-based drugs, a key advantage over other RNA based technologies. This collection of data attests to the versatility of the LNA Drug Platform and clearly supports Santaris Pharma A/S leadership position in discovering and developing RNA-targeted medicines."
In a talk titled, "Targeting miRNA-122 for the Treatment of HCV," Dr. Oerum will provide an update on the development of miravirsen, the first microRNA-targeted drug to enter clinical trials, which is now in Phase 2 studies to assess the safety and tolerability of the drug in treatment-naïve patients infected with HCV. Data from Phase 1 clinical studies with miravirsen in healthy volunteers show that the drug is well tolerated.
Previously published data in Science demonstrated that miravirsen successfully inhibited miR-122 and dramatically reduced Hepatitis C virus in the liver and in the bloodstream in chimpanzees chronically infected with the Hepatitis C virus(1). Because of its unique mechanism of action and tolerability profile, miravirsen has the potential to be an effective treatment option for patients with HCV.
In addition, scientists at Santaris Pharma A/S will present data using proprietary bioinformatics techniques to demonstrate the specificity of "tiny" 8-mer LNA-based compounds, which have shown to successfully inhibit entire microRNA families providing potential new approach for treating a range of diseases including cancer, viral infections, cardiovascular and muscle diseases. Recent data published in Nature Genetics showed that the high affinity and target specificity of tiny LNA-based compounds enabled functional inhibition of entire microRNA families in a range of tissues without off-target effects(2).
MicroRNAs have emerged as an important class of small regulatory RNAs encoded in the genome. They act to control the expression of sets of genes and entire pathways and are thus thought of as master regulators of gene expression associated with many diseases. Because they dictate the expression of fundamental regulatory pathways, microRNAs represent potential drug targets in the treatment of many disease processes.
Santaris Pharma A/S also will present data demonstrating successful "naked" delivery uptake of LNA-based compounds, an advantage over other RNA-based technologies that require complex delivery vehicles. Data showed that LNA-based compounds readily enter cells in an active form allowing in vitro prediction of potent therapeutically active compounds as well as in vivo distribution to manifold cell types and tissues. Without the need for using complex delivery vehicles, the versatility of the LNA Drug Platform is the key for scientists to develop both microRNA and mRNA-targeted drugs with excellent specificity and increased affinity to drug target, providing improved potency and favorable tissue-penetrating properties.
The Santaris Pharma A/S LNA Drug Platform is the only RNA technology with both mRNA and microRNA targeted drugs in clinical trials, demonstrating the broad utility of the proprietary platform. In September 2010, Santaris Pharma A/S successfully advanced miravirsen, a lead microRNA drug candidate targeting miR-122, into Phase 2 studies for the treatment of patients infected with the Hepatitis C virus. In addition, Santaris Pharma A/S also advanced two mRNA-targeted drugs, SPC5001 targeting PCSK9 and SPC4955 targeting apoB, for the treatment of high cholesterol into Phase 1 in May 2011.
With its partners, Santaris Pharma A/S has a robust product pipeline consisting of mRNA and microRNA drug discovery and development collaborations. These include partnerships with Pfizer, Inc. (delivery of lead candidates against up to 20 targets), miRagen Therapeutics (cardiovascular diseases), Shire plc (rare genetic disorders), GlaxoSmithKline (four viral disease drug candidates) and Enzon Pharmaceuticals (eight cancer targets successfully delivered - three are now in Phase 1 clinical studies).
About Locked Nucleic Acid (LNA) Drug Platform
The LNA Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combines the Company's proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver LNA-based drug candidates against RNA targets, both mRNA and microRNA, for a range of diseases including cardiometabolic disorders, infectious and inflammatory diseases, cancer and rare genetic disorders. LNA-based drugs are a promising new class of therapeutics that are enabling scientists to develop drug candidates to target pathways previously considered inaccessible. The LNA Drug Platform overcomes the limitations of earlier antisense and siRNA technologies to deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The unique combination of small size and very high affinity allows this new class of drugs candidates to potently and specifically inhibit RNA targets in many different tissues without the need for complex delivery vehicles. The most important features of LNA-based drugs include excellent specificity providing optimal targeting; increased affinity to targets providing improved potency; and favorable pharmacokinetic and tissue-penetrating properties that allow systemic delivery of these drugs without complex and potentially troublesome delivery vehicles.
About Santaris Pharma A/S
Santaris Pharma A/S is a privately held clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies. The Locked Nucleic Acid (LNA) Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combine the Company's proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The Company's research and development activities focus on infectious diseases and cardiometabolic disorders, while partnerships with major pharmaceutical companies include a range of therapeutic areas including cancer, cardiovascular disease, infectious and inflammatory diseases, and rare genetic disorders. The Company has strategic partnerships with miRagen Therapeutics, Shire plc, Pfizer, GlaxoSmithKline, and Enzon Pharmaceuticals. As part of its broad patent estate, the Company holds exclusive worldwide rights to all therapeutic uses of LNA. Santaris Pharma A/S, founded in 2003, is headquartered in Denmark with operations in the United States. Please visit http://www.santaris.com for more information.
(1) Lanford et al, Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327 (5962): 198-201
(2) Obad, et al. Silencing of microRNA families by seed-targeting tiny LNAs. Nature Genetics 10.1038/ng.786.
Tuesday, September 6, 2011
Anadys Pharmaceuticals' Steve Worland on the future of HCV drug development....
An excellent read here. Anadys Pharmaceuticals President and CEO Steve Worland gives us his take on the evolving HCV antiviral drug developmental landscape in this recent article published online in Xconomy. It's amazing how analogousness this development space is becoming to the early days of HIV. There are many notables in this article, including the mention of mathematical modeling that suggests that interferon-free regimens might be possible, but will need to contain three or four distinct antiviral mechanisms to result in a SVR without the emergence of resistance. I found his comparison of Anadys's HCV non-nuc setrobuvir to to the HIV non-nuc efavirenz to be interesting - his feeling is that, like efavirenz, setrobuvir's superior pharmacokinetics may be the answer to the inherent low barrier of resistance issues with the non-nuc class that have plagued other compounds such as Vertex's VX-222.
Dramatic Changes in Hepatitis C Treatment Expected to Continue
Steve Worland 9/6/11
Earlier this year the FDA approved telaprevir (Incivek) from Vertex Pharmaceuticals and boceprevir (Victrelis) from Merck for the treatment of hepatitis C. Both agents are protease inhibitors and represent the first approvals of direct acting antivirals for hepatitis C. Direct acting antivirals are a broad class of agents that act to block the growth of viruses by directly disrupting essential viral functions. The benefit of these drugs for hepatitis C follows the dramatic success of this class over the last 15 years in HIV. Now the future advances of direct acting antiviral therapy for hepatitis C is expected to follow a central theme of their use in HIV: that combination of multiple antivirals in a single treatment regimen will provide greater benefit than use of any one antiviral drug alone.
The new protease inhibitors were approved for use only in combination with two previously approved agents, pegylated interferon and ribavirin. The addition of either protease inhibitor increased clinical cure rates, known formally as sustained viral response (SVR) rates, by 30 to 40 percentage points over control groups receiving the standard pegylated interferon and ribavirin alone. As dramatic as these improvements are, there is a good chance for even more dramatic improvements if all-oral regimens, assembled by combining multiple direct acting antivirals, are able to maintain high cure rates while eliminating injectable interferon and its associated flu-like side effects that patients have long sought to avoid.
Next in the development queue are three agents that entered Phase III development this year, including two additional protease inhibitors (TMC435 from Johnson & Johnson’s Tibotec unit and BI201335 from Boehringer Ingelheim) and a cyclophilin inhibitor that disrupts a host function required for viral replication (alisporivir from Novartis). All three Phase III programs are exploring a modality similar to the approved agents, i.e. addition of a single new agent to the standard pegylated interferon/ribavirin. The ongoing Phase III programs will hope to demonstrate one or more advantage over the recently approved agents, potentially including better tolerability, further increases in cure rates, shorter duration of therapy and/or an increased proportion of patients successfully treated with shortened therapy. While such improvements may well be achieved, they may become less important or even irrelevant if the rapidly expanding number of direct acting antiviral combination trials leads to identification of new regimens that surpass all regimens that are based on a single antiviral drug added to the old standard regimen.
Investigation of direct acting antiviral combination regimens has exploded in the last 12 months. This advance has become possible because of the diversity of antiviral mechanisms distinct from protease inhibitors that are now represented in the pipeline of hepatitis C drugs in Phase II development across the industry. Diverse mechanisms are important because they typically provide distinct resistance profiles, and antiviral combinations are being assembled using new compounds with non-overlapping resistance profiles to provide a greater barrier to the development of antiviral resistance. Additional factors that are considered important in assembling optimal combinations include the safety and tolerability profile of each agent, compatible pharmacokinetic profiles and a low potential for unfavorable drug-drug interactions. The more extensively characterized each individual antiviral drug is, the lower the risk of an unanticipated negative interaction between the drugs once combined.
New mechanisms other than protease inhibitors that have entered large Phase IIb studies include non-nucleoside polymerase inhibitors (setrobuvir from my company, Anadys Pharmaceuticals, as well as tegobuvir from Gilead Sciences and filibuvir from Pfizer). Another class is composed of nucleoside/tide polymerase inhibitors (mericitabine from Roche and PSI-7997 from Pharmasset). There’s also an NS5a inhibitor in Phase IIb development (BMS-790052 from Bristol-Myers Squibb).
At Anadys, we chose to focus on the non-nucleoside class of polymerase inhibitors for several reasons. We recognized an inherent potential for an excellent safety profile, given the absence of structurally related host targets and the ability to generate inhibitors without relying on close analogs of host metabolites. The excellent safety record to date for setrobuvir is consistent with our initial expectations regarding safety. The diversity of applicable chemotypes also led us to expect a clear path to patent-protected intellectual property, exemplified by our recently issued U.S. patent covering setrobuvir. In other antiviral drug classes, especially nucleosides/tides and NS5a inhibitors, the range of useful chemical space discovered to date is considerably more narrow, leading to the potential for more interference on the IP side. Lastly, we recognized that a potential liability of the non-nucleoside class, a lower genetic barrier to resistance, could likely be addressed if we were able to engineer a high pharmacological barrier to resistance into candidate molecules. This recognition was based on the lessons learned about non-nucleosides in the 1990s in HIV. Specifically, there were two disappointing product introductions of non-nucleoside products for HIV that were plagued with rapid emergence of resistance—nevirapine (Viramune) from Boehinger Ingelheim and delavirdine (Rescriptor), now marketed by Pfizer. After that came efavirenz (Sustiva) from Bristol-Myers Squibb, so named for its ability to last longer in the bloodstream, which demonstrated that a non-nucleoside with good potency and a prolonged plasma half-life could demonstrate a dramatically improved resistance profile. While we reasoned that a similar solution would be applicable in hepatitis C, we also understood the significant medicinal chemistry challenge to accomplish this objective and furthermore understood that the technology platform at Anadys was exquisitely well matched to the molecular engineering challenge of simultaneously optimizing potency and pharmacokinetics. The excellent resistance profile of setrobuvir observed to date demonstrates the high pharmacological resistance barrier achieved with setrobuvir, and data to date is consistent with our idea that a high pharmacological barrier to resistance could serve in place of a high genetic barrier to resistance.
As the hepatitis C development landscape continues to advance, we expect to see an increasing number of direct acting antiviral combination trials and subsequent approval of new agents based on data derived from such trials. The FDA as well as patient advocacy groups have been strong proponents of investigating antiviral drug combinations prior to approval of individual components, and I expect an ongoing favorable regulatory environment towards combination trials provided that each individual agent is sufficiently well-characterized.
Companies that believe in the importance of antiviral combinations for future commercial relevance in hepatitis C are likely to have opinions as to how many drugs they believe will be needed in antiviral combination regimens, and are likely to pursue strategies directed at accessing at least that number of compounds if not a greater number as insurance against attrition. Mathematical modeling from Perelson and colleagues suggests that interferon-free regimens will need to contain three or four distinct antiviral mechanisms to result in viral eradication (SVR) prior to emergence of resistance. To access the required number of drugs, companies have several business alternatives available. They can rely on maturation of their internal pipelines, although few if any companies appear today to have sufficiently robust internal pipelines to rely exclusively on this approach. Companies can rely on cross-company clinical collaboration agreements to gain initial data on particular antiviral combinations, although this approach doesn’t directly answer the question of how to seek approval and launch effective marketing efforts for the individual components studied in a cross-company antiviral drug combination trial. Companies with antiviral drugs other than protease inhibitors can look to utilize one of the approved protease inhibitors as one other mechanism, analogous to the use of interferon and ribavirin in the development of the protease inhibitors to date, but this will only be a partial solution if three or more DAAs are required. Lastly, companies can gain exclusive access to antiviral drugs outside their current pipelines through a variety of business deals, allowing them to quickly assemble a pipeline with sufficient depth to increase the chances of being early to market with a successful combination regimen. To date, examples of all these strategies except combination with one of the approved protease inhibitors have been pursued by one or more companies. Going forward, these efforts across the industry are likely to culminate in approval of direct acting antiviral combination regimens, with the ultimate goal of assembling combinations powerful enough to eliminate interferon and perhaps ribavirin from hepatitis C therapy. These advancements may occur within the next few years, and if realized, would represent yet another dramatic improvement in hepatitis C therapy, at least as dramatic as the advances recently realized with the approval of the first protease inhibitors.
Steve Worland is the president and CEO of San Diego-based Anadys Pharmaceuticals.
Dramatic Changes in Hepatitis C Treatment Expected to Continue
Steve Worland 9/6/11
Earlier this year the FDA approved telaprevir (Incivek) from Vertex Pharmaceuticals and boceprevir (Victrelis) from Merck for the treatment of hepatitis C. Both agents are protease inhibitors and represent the first approvals of direct acting antivirals for hepatitis C. Direct acting antivirals are a broad class of agents that act to block the growth of viruses by directly disrupting essential viral functions. The benefit of these drugs for hepatitis C follows the dramatic success of this class over the last 15 years in HIV. Now the future advances of direct acting antiviral therapy for hepatitis C is expected to follow a central theme of their use in HIV: that combination of multiple antivirals in a single treatment regimen will provide greater benefit than use of any one antiviral drug alone.
The new protease inhibitors were approved for use only in combination with two previously approved agents, pegylated interferon and ribavirin. The addition of either protease inhibitor increased clinical cure rates, known formally as sustained viral response (SVR) rates, by 30 to 40 percentage points over control groups receiving the standard pegylated interferon and ribavirin alone. As dramatic as these improvements are, there is a good chance for even more dramatic improvements if all-oral regimens, assembled by combining multiple direct acting antivirals, are able to maintain high cure rates while eliminating injectable interferon and its associated flu-like side effects that patients have long sought to avoid.
Next in the development queue are three agents that entered Phase III development this year, including two additional protease inhibitors (TMC435 from Johnson & Johnson’s Tibotec unit and BI201335 from Boehringer Ingelheim) and a cyclophilin inhibitor that disrupts a host function required for viral replication (alisporivir from Novartis). All three Phase III programs are exploring a modality similar to the approved agents, i.e. addition of a single new agent to the standard pegylated interferon/ribavirin. The ongoing Phase III programs will hope to demonstrate one or more advantage over the recently approved agents, potentially including better tolerability, further increases in cure rates, shorter duration of therapy and/or an increased proportion of patients successfully treated with shortened therapy. While such improvements may well be achieved, they may become less important or even irrelevant if the rapidly expanding number of direct acting antiviral combination trials leads to identification of new regimens that surpass all regimens that are based on a single antiviral drug added to the old standard regimen.
Investigation of direct acting antiviral combination regimens has exploded in the last 12 months. This advance has become possible because of the diversity of antiviral mechanisms distinct from protease inhibitors that are now represented in the pipeline of hepatitis C drugs in Phase II development across the industry. Diverse mechanisms are important because they typically provide distinct resistance profiles, and antiviral combinations are being assembled using new compounds with non-overlapping resistance profiles to provide a greater barrier to the development of antiviral resistance. Additional factors that are considered important in assembling optimal combinations include the safety and tolerability profile of each agent, compatible pharmacokinetic profiles and a low potential for unfavorable drug-drug interactions. The more extensively characterized each individual antiviral drug is, the lower the risk of an unanticipated negative interaction between the drugs once combined.
New mechanisms other than protease inhibitors that have entered large Phase IIb studies include non-nucleoside polymerase inhibitors (setrobuvir from my company, Anadys Pharmaceuticals, as well as tegobuvir from Gilead Sciences and filibuvir from Pfizer). Another class is composed of nucleoside/tide polymerase inhibitors (mericitabine from Roche and PSI-7997 from Pharmasset). There’s also an NS5a inhibitor in Phase IIb development (BMS-790052 from Bristol-Myers Squibb).
At Anadys, we chose to focus on the non-nucleoside class of polymerase inhibitors for several reasons. We recognized an inherent potential for an excellent safety profile, given the absence of structurally related host targets and the ability to generate inhibitors without relying on close analogs of host metabolites. The excellent safety record to date for setrobuvir is consistent with our initial expectations regarding safety. The diversity of applicable chemotypes also led us to expect a clear path to patent-protected intellectual property, exemplified by our recently issued U.S. patent covering setrobuvir. In other antiviral drug classes, especially nucleosides/tides and NS5a inhibitors, the range of useful chemical space discovered to date is considerably more narrow, leading to the potential for more interference on the IP side. Lastly, we recognized that a potential liability of the non-nucleoside class, a lower genetic barrier to resistance, could likely be addressed if we were able to engineer a high pharmacological barrier to resistance into candidate molecules. This recognition was based on the lessons learned about non-nucleosides in the 1990s in HIV. Specifically, there were two disappointing product introductions of non-nucleoside products for HIV that were plagued with rapid emergence of resistance—nevirapine (Viramune) from Boehinger Ingelheim and delavirdine (Rescriptor), now marketed by Pfizer. After that came efavirenz (Sustiva) from Bristol-Myers Squibb, so named for its ability to last longer in the bloodstream, which demonstrated that a non-nucleoside with good potency and a prolonged plasma half-life could demonstrate a dramatically improved resistance profile. While we reasoned that a similar solution would be applicable in hepatitis C, we also understood the significant medicinal chemistry challenge to accomplish this objective and furthermore understood that the technology platform at Anadys was exquisitely well matched to the molecular engineering challenge of simultaneously optimizing potency and pharmacokinetics. The excellent resistance profile of setrobuvir observed to date demonstrates the high pharmacological resistance barrier achieved with setrobuvir, and data to date is consistent with our idea that a high pharmacological barrier to resistance could serve in place of a high genetic barrier to resistance.
As the hepatitis C development landscape continues to advance, we expect to see an increasing number of direct acting antiviral combination trials and subsequent approval of new agents based on data derived from such trials. The FDA as well as patient advocacy groups have been strong proponents of investigating antiviral drug combinations prior to approval of individual components, and I expect an ongoing favorable regulatory environment towards combination trials provided that each individual agent is sufficiently well-characterized.
Companies that believe in the importance of antiviral combinations for future commercial relevance in hepatitis C are likely to have opinions as to how many drugs they believe will be needed in antiviral combination regimens, and are likely to pursue strategies directed at accessing at least that number of compounds if not a greater number as insurance against attrition. Mathematical modeling from Perelson and colleagues suggests that interferon-free regimens will need to contain three or four distinct antiviral mechanisms to result in viral eradication (SVR) prior to emergence of resistance. To access the required number of drugs, companies have several business alternatives available. They can rely on maturation of their internal pipelines, although few if any companies appear today to have sufficiently robust internal pipelines to rely exclusively on this approach. Companies can rely on cross-company clinical collaboration agreements to gain initial data on particular antiviral combinations, although this approach doesn’t directly answer the question of how to seek approval and launch effective marketing efforts for the individual components studied in a cross-company antiviral drug combination trial. Companies with antiviral drugs other than protease inhibitors can look to utilize one of the approved protease inhibitors as one other mechanism, analogous to the use of interferon and ribavirin in the development of the protease inhibitors to date, but this will only be a partial solution if three or more DAAs are required. Lastly, companies can gain exclusive access to antiviral drugs outside their current pipelines through a variety of business deals, allowing them to quickly assemble a pipeline with sufficient depth to increase the chances of being early to market with a successful combination regimen. To date, examples of all these strategies except combination with one of the approved protease inhibitors have been pursued by one or more companies. Going forward, these efforts across the industry are likely to culminate in approval of direct acting antiviral combination regimens, with the ultimate goal of assembling combinations powerful enough to eliminate interferon and perhaps ribavirin from hepatitis C therapy. These advancements may occur within the next few years, and if realized, would represent yet another dramatic improvement in hepatitis C therapy, at least as dramatic as the advances recently realized with the approval of the first protease inhibitors.
Steve Worland is the president and CEO of San Diego-based Anadys Pharmaceuticals.
Monday, September 5, 2011
Gilead Sciences amends study by haltting doseing of GS 9190...
Gilead amends HCV study by halting dosing of polymerase inhibitor GS 9190 in combination with SOC and protease inhibitors...
(Because of two serious advents in two different studyies looking a a 'quad' combination of polymerase inhibitor GS 9190 + peg-INF-RBV + either investigational protease inhibitors GS 9451 or GS 9256, Gilead has halted dosing of GS 9190 in those particular studies. Studies of a interferon-free, all-oral regimen continue, however. )
Sept. 4, 2011, 11:00 a.m. EDT
Gilead Amends Study Design for Ongoing Hepatitis C Clinical Trials That Include GS 9190, Pegylated Interferon and Ribavirin, and Another Direct-Acting Antiviral Agent
Change Does Not Affect Ongoing "All Oral" Clinical Trials Evaluating Multiple Direct-Acting Antivirals in Combination
FOSTER CITY, Calif., Sep 04, 2011 (BUSINESS WIRE) -- Gilead Sciences, Inc. /quotes/zigman/72849/quotes/nls/gild GILD -1.90% today announced that, in consultation with the U.S. Food and Drug Administration (FDA), the company will amend the design of ongoing clinical trials to discontinue dosing of GS 9190 in hepatitis C-infected patients who are receiving that compound in combination with pegylated interferon and ribavirin, and another direct-acting antiviral agent.
This decision follows reports of two serious adverse events in patients enrolled in two separate studies who were receiving a four-drug regimen of GS 9190, an investigational HCV NS5B polymerase inhibitor; pegylated interferon and ribavirin; and one of two protease inhibitors (GS 9451 in one study and GS 9256 in the second study). Patient safety is Gilead's top priority, and the company will therefore immediately halt the dosing of GS 9190 in patients receiving this combination of medications.
Pegylated interferon in combination with ribavirin is currently part of the standard of care treatment for patients with chronic hepatitis C. Because of the side effects that can be associated with interferon, Gilead is working to develop multiple oral antivirals that, when used in combination, may be able to reduce or eliminate the need for interferon.
Gilead does not anticipate any impact on the timelines for or goals of its planned and ongoing clinical studies evaluating an "all oral" regimen for the treatment of chronic hepatitis C. Studies that include GS 9190 but do not include pegylated interferon will continue as planned. Similarly, studies that include the combination of GS 9451 (an investigational protease inhibitor), GS 5885 (an investigational NS5A) and pegylated interferon and ribavirin will continue.
Please click on the attached link for entire press release.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.
Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors that could cause actual results to differ materially from those referred to in the forward-looking statements, including the risk that further analysis of the laboratory abnormalities, adverse events and other data obtained to date may not support the continued development of GS 9190 and the risk that further clinical testing of Gilead's developmental compounds (including GS 9190, GS 9451, GS 5885 and GS 9256) and all oral regimens containing such compounds result in laboratory abnormalities, adverse events and other clinical data that may not support the continued development of such compounds or regimens. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended June 30, 2011, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
For more information on Gilead Sciences, please visit the company's website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
SOURCE: Gilead Sciences, Inc.
(Because of two serious advents in two different studyies looking a a 'quad' combination of polymerase inhibitor GS 9190 + peg-INF-RBV + either investigational protease inhibitors GS 9451 or GS 9256, Gilead has halted dosing of GS 9190 in those particular studies. Studies of a interferon-free, all-oral regimen continue, however. )
Sept. 4, 2011, 11:00 a.m. EDT
Gilead Amends Study Design for Ongoing Hepatitis C Clinical Trials That Include GS 9190, Pegylated Interferon and Ribavirin, and Another Direct-Acting Antiviral Agent
Change Does Not Affect Ongoing "All Oral" Clinical Trials Evaluating Multiple Direct-Acting Antivirals in Combination
FOSTER CITY, Calif., Sep 04, 2011 (BUSINESS WIRE) -- Gilead Sciences, Inc. /quotes/zigman/72849/quotes/nls/gild GILD -1.90% today announced that, in consultation with the U.S. Food and Drug Administration (FDA), the company will amend the design of ongoing clinical trials to discontinue dosing of GS 9190 in hepatitis C-infected patients who are receiving that compound in combination with pegylated interferon and ribavirin, and another direct-acting antiviral agent.
This decision follows reports of two serious adverse events in patients enrolled in two separate studies who were receiving a four-drug regimen of GS 9190, an investigational HCV NS5B polymerase inhibitor; pegylated interferon and ribavirin; and one of two protease inhibitors (GS 9451 in one study and GS 9256 in the second study). Patient safety is Gilead's top priority, and the company will therefore immediately halt the dosing of GS 9190 in patients receiving this combination of medications.
Pegylated interferon in combination with ribavirin is currently part of the standard of care treatment for patients with chronic hepatitis C. Because of the side effects that can be associated with interferon, Gilead is working to develop multiple oral antivirals that, when used in combination, may be able to reduce or eliminate the need for interferon.
Gilead does not anticipate any impact on the timelines for or goals of its planned and ongoing clinical studies evaluating an "all oral" regimen for the treatment of chronic hepatitis C. Studies that include GS 9190 but do not include pegylated interferon will continue as planned. Similarly, studies that include the combination of GS 9451 (an investigational protease inhibitor), GS 5885 (an investigational NS5A) and pegylated interferon and ribavirin will continue.
Please click on the attached link for entire press release.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.
Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors that could cause actual results to differ materially from those referred to in the forward-looking statements, including the risk that further analysis of the laboratory abnormalities, adverse events and other data obtained to date may not support the continued development of GS 9190 and the risk that further clinical testing of Gilead's developmental compounds (including GS 9190, GS 9451, GS 5885 and GS 9256) and all oral regimens containing such compounds result in laboratory abnormalities, adverse events and other clinical data that may not support the continued development of such compounds or regimens. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended June 30, 2011, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
For more information on Gilead Sciences, please visit the company's website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
SOURCE: Gilead Sciences, Inc.
Thursday, September 1, 2011
TMC435 Phase III Trials for genotype-1 HCV patients completely enrolled...
(Medivir/Tibotec clinical trials for their HCV protease inhibitor TMC435(QUEST 1 and QUEST 2 for genotype 1 tx-naive patients and PROMISE for tx-experienced relapsers) are fully enrolled. Good news for everybody. The companies continue to build anticipation for the start and eventual interim data looking Medivir/Tibotec/Pharmasset's proof-of-concept oral, interferon-free phase 2 trial, looking at a TMC435 and PSI-7977 combo. An all-oral, once-daily regimen would be a tremendous accomplishment.)
Medivir: Completed Enrollment of Three Global Phase 3 Trials for TMC435 in Chronic Hepatitis C Genotype-1 Infected Patients
HUDDINGE, Sweden, Aug 31, 2011 (BUSINESS WIRE) -- Regulatory News:
MedivirAB (omx:MVIR) is an emerging research-based specialty pharmaceutical company focused on infectious diseases.
Medivir today announced that its investigational protease inhibitor TMC435, developed by Tibotec Pharmaceuticals, has successfully completed enrollment of three ongoing global phase 3 trials and further reports that all patients are now on TMC435 or active control treatment. The trials are QUEST 1 and QUEST 2, in treatment naive patients, and PROMISE in the treatment experienced relapser patient population. In all three trials, the duration of total treatment is response guided and patients in the TMC435 arms are eligible to stop all treatment at week 24 if predefined response-guided criteria are met.
Medivir recently announced that TMC435 had received "Fast Track" designation by the U.S. Food and Drug Administration ("FDA") for the treatment of chronic hepatitis C (CHC) genotype-1 infection. This is based on TMC435's potential to address unmet medical needs in the treatment of chronic HCV infection.
In parallel to these trials, phase 3 studies for TMC435 in Japan, in both treatment naive and treatment experienced hepatitis C genotype-1 infected patients, have also completed enrollment.
Global Phase 3 Program in brief:
- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
Bertil Samuelsson, Chief Scientific Advisor at Medivir, comments - "We are extremely excited to have completed the enrollment and patient dosing in three large global phase 3 trials. It is a monumental milestone step for Medivir as a company and for TMC435 progress towards market registration. The completed enrollment of phase 3 studies for TMC435 in Japan represents another key project milestone achievement."
About TMC435
TMC435, an investigational CHC protease inhibitor currently in phase 3 clinical development, is a highly potent, selective and safe once-daily (q.d.) drug jointly developed by Tibotec Pharmaceuticals to treat chronic hepatitis C virus infections.
TMC435 is being developed both in combination with PegIFN/RBV and in combination with Direct-acting Antiviral (DAA) agents without peginterferon and with or without ribavirin (RBV).
In June 2011 the combination study of TMC435 with TMC647055, a non-nucleoside NS5B polymerase inhibitor being developed by Tibotec Pharmaceuticals, was initiated and in July 2011 Medivir confirmed the intention to start a proof-of-concept oral, interferon-free phase 2 trial, investigating the combination of TMC435 and Pharmasset's PSI-7977, a once daily nucleotide NS5B polymerase inhibitor. Phase 3 programs for TMC435 are also ongoing in Japan.
In parallel with the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
For additional information from these studies, please see www.medivir.com and www.clinicaltrials.gov
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a novel protease inhibitor is in phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia to ensure timely commercialization of TMC435 in the Nordic markets, once approved.
Medivir's first product, the unique cold sore product Xerese(R)/Xerclear(R) was launched on the US market in February 2011. Xerese(R)/Xerclear(R), which has been approved in both the US and Europe is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia. Rights in North America, Canada and Mexico have recently been sold to Meda AB. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: www.medivir.com
This information was brought to you by Cision http://www.cisionwire.com
SOURCE: Medivir
Medivir: Completed Enrollment of Three Global Phase 3 Trials for TMC435 in Chronic Hepatitis C Genotype-1 Infected Patients
HUDDINGE, Sweden, Aug 31, 2011 (BUSINESS WIRE) -- Regulatory News:
MedivirAB (omx:MVIR) is an emerging research-based specialty pharmaceutical company focused on infectious diseases.
Medivir today announced that its investigational protease inhibitor TMC435, developed by Tibotec Pharmaceuticals, has successfully completed enrollment of three ongoing global phase 3 trials and further reports that all patients are now on TMC435 or active control treatment. The trials are QUEST 1 and QUEST 2, in treatment naive patients, and PROMISE in the treatment experienced relapser patient population. In all three trials, the duration of total treatment is response guided and patients in the TMC435 arms are eligible to stop all treatment at week 24 if predefined response-guided criteria are met.
Medivir recently announced that TMC435 had received "Fast Track" designation by the U.S. Food and Drug Administration ("FDA") for the treatment of chronic hepatitis C (CHC) genotype-1 infection. This is based on TMC435's potential to address unmet medical needs in the treatment of chronic HCV infection.
In parallel to these trials, phase 3 studies for TMC435 in Japan, in both treatment naive and treatment experienced hepatitis C genotype-1 infected patients, have also completed enrollment.
Global Phase 3 Program in brief:
- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
Bertil Samuelsson, Chief Scientific Advisor at Medivir, comments - "We are extremely excited to have completed the enrollment and patient dosing in three large global phase 3 trials. It is a monumental milestone step for Medivir as a company and for TMC435 progress towards market registration. The completed enrollment of phase 3 studies for TMC435 in Japan represents another key project milestone achievement."
About TMC435
TMC435, an investigational CHC protease inhibitor currently in phase 3 clinical development, is a highly potent, selective and safe once-daily (q.d.) drug jointly developed by Tibotec Pharmaceuticals to treat chronic hepatitis C virus infections.
TMC435 is being developed both in combination with PegIFN/RBV and in combination with Direct-acting Antiviral (DAA) agents without peginterferon and with or without ribavirin (RBV).
In June 2011 the combination study of TMC435 with TMC647055, a non-nucleoside NS5B polymerase inhibitor being developed by Tibotec Pharmaceuticals, was initiated and in July 2011 Medivir confirmed the intention to start a proof-of-concept oral, interferon-free phase 2 trial, investigating the combination of TMC435 and Pharmasset's PSI-7977, a once daily nucleotide NS5B polymerase inhibitor. Phase 3 programs for TMC435 are also ongoing in Japan.
In parallel with the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
For additional information from these studies, please see www.medivir.com and www.clinicaltrials.gov
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a novel protease inhibitor is in phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia to ensure timely commercialization of TMC435 in the Nordic markets, once approved.
Medivir's first product, the unique cold sore product Xerese(R)/Xerclear(R) was launched on the US market in February 2011. Xerese(R)/Xerclear(R), which has been approved in both the US and Europe is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia. Rights in North America, Canada and Mexico have recently been sold to Meda AB. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: www.medivir.com
This information was brought to you by Cision http://www.cisionwire.com
SOURCE: Medivir
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