(Article from Medscape on IAS presentation culling data from the SPRINT-2 and RESPOND-2 trails that find that genotype 1a patients have a lower barrier to resistance than genotype 1b. This was also found to be true for Telaprevir as well)
Genotype 1b HCV Patients Fare Better on Boceprevir
Emma Hitt, PhD
July 22, 2011 (Rome, Italy) — Boceprevir/peginterferon plus ribavirin is associated with a small but consistently higher sustained viral response (SVR) rate and a lower rate of development of boceprevir-related resistance-associated variants (RAVs) in patients infected with hepatitis C virus (HCV) genotype 1b subtype than in those infected with genotype 1a subtype, according to new data from the SPRINT-2 and RESPOND-2 phase 3 trials.
Daria Hazuda, PhD, vice president of virus and cell biology at Merck Research Laboratories, in Whitehouse Station, New Jersey, presented the findings in a late-breaking oral session here at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.
"It was important to do this study in order to better understand the development of resistance with boceprevir," Dr. Hazuda told Medscape Medical News. "Additional analyses of our clinical studies with boceprevir are ongoing. A 3.5-year long-term follow-up study is underway to evaluate the persistence of resistance-associated variants over time," she added.
Dr. Daria Hazuda
In the SPRINT-2 and RESPOND-2 clinical trials, Dr. Hazuda and colleagues compared the SVR to boceprevir in combination with pegylated-interferon alfa-2b plus ribavirin and the associated presence or absence of RAVs between patients with HCV genotype 1a and those with genotype 1b.
The rate of SVR among those receiving boceprevir in the 2 trials was higher in patients with genotype 1b than in those with genotype 1a (66%–73% vs 59%–64%). The number of patients with RAVs detected was higher in genotype 1a patients than in genotype 1b patients in SPRINT-2 (58% vs 48%) and in RESPOND-2 (48% vs 41%).
The researchers also found that the RAVs V36M and R155K were more common in genotype 1a patients, whereas T54A/S, A156S, and V170A were more common in genotype 1b patients.
RAVs were more common in patients with a poor interferon response (defined as a decline in viral load of less than 1 log at week 4) than in those with a good interferon response (a decline in viral load of 1 log or more at week 4) (68% vs 31%). Overall, baseline samples showed a low rate of RAVs, and most patients with RAVs still achieved SVR.
"Understanding which mutations develop and how long they persist may help us assess the potential for retreatment with first-generation protease inhibitors and, importantly, facilitate the development of next-generation protease inhibitors that can work effectively against resistant mutants," Dr. Hazuda explained.
According to Dr. Hazuda, the resistance variants observed with boceprevir are similar, if not identical, to those observed with telaprevir. "Although we do not know if retreatment will be possible, there should be no difference between these 2 first-generation protease inhibitors," she said.
Dr. Hazuda added that it is still not known how long these resistant variants last, or whether the viral population has been altered in a way to make it less likely that patients will respond to retreatment with another first-generation protease inhibitor.
"These are valuable phase 3 trial data, which emphasize the fact that the main determinant of the SVR is not the preexistence of RAVs at baseline but the response to interferon and ribavirin," said independent commentator Jean-Michel Pawlotsky, MD, professor of medicine at the University of Paris-Est, director of the Department of Virology at the Henri Mondor University Hospital in Créteil, France, and director of the Department of Molecular Virology and Immunology at the Mondor Institute of Biomedical Research.
"Patients and doctors should not be afraid of resistance to protease inhibitors," he told Medscape Medical News. "Hepatitis remains theoretically curable in 100% of cases, and new drugs will allow patients who failed on triple-combination therapy the opportunity for treatment in the future," he added.
The study was funded Merck and Co. Dr. Hazuda is an employee of Merck. Dr. Pawlotsky reports acting as a consultant to Vertex, Jannsen, Merck, and Roche.
6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract WELBX04. Presented July 20, 2011.
Medscape Medical News © 2011 WebMD, LLC
Send comments and news tips to news@medscape.net.
Showing posts with label HCV therapy. Show all posts
Showing posts with label HCV therapy. Show all posts
Friday, July 22, 2011
Wednesday, June 22, 2011
Medivir/Tibotec's NS5B Inhibitor TMC649128 starts Phase 1b trial....
TMC649128, a nucleoside inhibitor jointly developed between Sweden's Medivir and Tibotec heads for the clinic in this early stage Phase 1b trial
Huddinge, Sweden - Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, today announces the start of a phase Ib clinical trial with TMC649128 intended for the treatment of chronic hepatitis C virus (HCV) infection.
TMC649128 is a nucleoside NS5B polymerase inhibitor developed in collaboration with Tibotec Pharmaceuticals. TMC649128 has demonstrated an attractive pre-clinical profile and displays in vitro activity across multiple HCV genotypes and a high genetic barrier to resistance. A clinical phase Ia double-blind, randomized, placebo-controlled single-ascending dose trial to assess the safety, tolerability and pharmacokinetics in healthy volunteers has now successfully been completed.
The TMC649128 phase Ib study that now is underway is a double-blind, randomized and placebo-controlled trial in genotype 1 HCV-infected patients to evaluate the safety, tolerability, pharmacokinetics and antiviral activity of multiple ascending doses of TMC649128 given as monotherapy and in combination with pegylated interferon and ribavirin.
It is anticipated that TMC649128 will be used in combination with other HCV direct acting antiviral agents, given its high genetic barrier to resistance and antiviral activity across multiple HCV genotypes.
“We are delighted to see TMC649128, our first HCV nucleoside inhibitor, advance into clinical phase Ib studies in HCV patients”, stated Bertil Samuelsson, CSO of Medivir. "The start of this phase Ib trial underscores our commitment to develop new and innovative treatments for hepatitis C infected patients. We view nucleoside inhibitors, such as TMC649128, and protease inhibitors, such as TMC435, as cornerstone components of future direct acting antiviral combinations for HCV therapy.”
For more information about Medivir, please contact;
Medivir (www.medivir.se)
Rein Piir, CFO & VP Investor Relations
Mobile: +46 708 537 292
M:CommunicationsEurope: Mary-Jane Elliott / Amber Bielecka / Katja Toon Medivir@mcomgroup.com
+44(0)20 7920 2330
USA: Roland Tomforde +1 212 232 2356
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’s Commitment to HCV
Medivir and Tibotec are also jointly developing the once daily protease inhibitor TMC435 for treatment of hepatitis C virus infections (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. Medivir has a strong R&D portfolio and has recently launched its first product Xerese™/Xerclear®.
Medivir’s key pipeline asset, TMC435, a protease inhibitor, is in global phase 3 clinical development for Hepatitis C and is partnered with Tibotec Pharmaceuticals.
Xerese™/Xerclear® is an innovative treatment for cold sores, which has been approved in both the US and Europe. It is partnered with GlaxoSmithKline to be sold OTC in Europe and Russia and with Meda AB in North America. Medivir has retained the Rx rights for Xerclear® in Sweden and Finland.
For more information about Medivir, please visit the Company’s website: www.medivir.se.
Huddinge, Sweden - Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, today announces the start of a phase Ib clinical trial with TMC649128 intended for the treatment of chronic hepatitis C virus (HCV) infection.
TMC649128 is a nucleoside NS5B polymerase inhibitor developed in collaboration with Tibotec Pharmaceuticals. TMC649128 has demonstrated an attractive pre-clinical profile and displays in vitro activity across multiple HCV genotypes and a high genetic barrier to resistance. A clinical phase Ia double-blind, randomized, placebo-controlled single-ascending dose trial to assess the safety, tolerability and pharmacokinetics in healthy volunteers has now successfully been completed.
The TMC649128 phase Ib study that now is underway is a double-blind, randomized and placebo-controlled trial in genotype 1 HCV-infected patients to evaluate the safety, tolerability, pharmacokinetics and antiviral activity of multiple ascending doses of TMC649128 given as monotherapy and in combination with pegylated interferon and ribavirin.
It is anticipated that TMC649128 will be used in combination with other HCV direct acting antiviral agents, given its high genetic barrier to resistance and antiviral activity across multiple HCV genotypes.
“We are delighted to see TMC649128, our first HCV nucleoside inhibitor, advance into clinical phase Ib studies in HCV patients”, stated Bertil Samuelsson, CSO of Medivir. "The start of this phase Ib trial underscores our commitment to develop new and innovative treatments for hepatitis C infected patients. We view nucleoside inhibitors, such as TMC649128, and protease inhibitors, such as TMC435, as cornerstone components of future direct acting antiviral combinations for HCV therapy.”
For more information about Medivir, please contact;
Medivir (www.medivir.se)
Rein Piir, CFO & VP Investor Relations
Mobile: +46 708 537 292
M:CommunicationsEurope: Mary-Jane Elliott / Amber Bielecka / Katja Toon Medivir@mcomgroup.com
+44(0)20 7920 2330
USA: Roland Tomforde +1 212 232 2356
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’s Commitment to HCV
Medivir and Tibotec are also jointly developing the once daily protease inhibitor TMC435 for treatment of hepatitis C virus infections (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. Medivir has a strong R&D portfolio and has recently launched its first product Xerese™/Xerclear®.
Medivir’s key pipeline asset, TMC435, a protease inhibitor, is in global phase 3 clinical development for Hepatitis C and is partnered with Tibotec Pharmaceuticals.
Xerese™/Xerclear® is an innovative treatment for cold sores, which has been approved in both the US and Europe. It is partnered with GlaxoSmithKline to be sold OTC in Europe and Russia and with Meda AB in North America. Medivir has retained the Rx rights for Xerclear® in Sweden and Finland.
For more information about Medivir, please visit the Company’s website: www.medivir.se.
Tuesday, April 12, 2011
Medco database analysis says patients on antidepressants more likely to be adherent to HCV treatment...
Interesting study from the Medco folks, published in the American Journal of Managed Care and presented recently at the 2011 International Conference on Viral Hepatitis. Medco used de-personalized data from their drug claims database to look at 3,607 patients newly Rx'd Peg-interferon and ribavirin for treatment of HCV. They evaluated adherence using a ratio called the 'medication possession ratio' or MPR, which measures the percent of time that HCV patients had medication available for their use. Patients with a MPR that was equal or greater than 80% were considered adherent. The study found that among patients with HCV who were both on HCV therapy and using an antidepressant, 68.5 percent were adherent. Grant it, database studies - like any study - comes with it's own inherent biases and it's hard to gather what other extraneous variables might have had impact on adherence, such as support groups, family support system, physician or mid-level check-ins, etc. Still, pretty impactful and compelling data that makes sense - if you feel better, one can assume that you'd feel more compelled to take one's medication.
BALTIMORE, April 11, 2011 /PRNewswire/ -- Adherence to interferon, an important medication used to treat Hepatitis C, is critical to successfully clearing the virus that causes the disease. A new observational analysis by Medco Health Solutions, Inc. (NYSE: MHS) finds that when Hepatitis C patients are also being treated for depression -- a frequent side effect of interferon use -- they are more likely to remain on their interferon therapy. The analysis is being presented today at the International Conference on Viral Hepatitis 2011.
According to the study, approximately 40 percent of Hepatitis C patients on interferon and ribavirin -- an antiviral medication used in combination with interferon -- were not adherent to their medication regimen. This puts patients at risk for progression of their disease due to their inability to eliminate the virus. The research found that the patients also using an antidepressant had the highest rates of adherence to their Hepatitis C treatment. Among patients with Hepatitis C who were using an antidepressant, 68.5 percent were adherent to their interferon therapy. For patients being treated for both Hepatitis C and HIV, 77.3 percent taking antidepressants were properly complying with their interferon therapy. Overall, 46 percent of patients with Hepatitis C were on an antidepressant.
"A common side-effect of interferon is depression, but little research has been done looking at the impact of treating depression on a patient's adherence with their Hepatitis C medications," said Mary Cassler RPh, Director of Clinical Innovation in Medco's Advanced Clinical Science and Research Group, who conducted the analysis. "These findings point to the need to proactively screen patients on interferon for depression and make sure that those who show signs of depression receive the proper interventions."
The usual course of interferon therapy for patients with Hepatitis C lasts either 24 or 48 weeks depending on the genotype of the virus, which influences the duration of treatment. Patients who discontinue use of the medication before treatment is completed, or those who do not take their medication as prescribed, frequently need to be retreated. Patients who fail to completely eliminate the virus have a higher risk of developing liver cancer. According to a study published in the American Journal of Managed Care, therapy can cost more than $40,000 per patient.
"Depression, whether interferon-induced or a separate co-morbid condition, can sabotage efforts to effectively treat Hepatitis C," said Dr. David Muzina, National Practice Leader, Medco Neuroscience Therapeutic Resource Center®. "All health care professionals, including pharmacists, need to know how to detect depression and work together to support safe, effective and affordable treatments."
Details
The analysis reviewed de-identified prescription drug claims from Medco's database and identified 3,607 patients who were newly prescribed interferon and ribavirin to treat Hepatitis C. Among the Hepatitis C patients who were identified, only 1,657 were being treated for depression. For the 109 patients who were also co-infected with HIV, 66 were on an antidepressant.
Adherence was evaluated by using the medication possession ratio (MPR) which measures the percent of time that patients have medication available for their use. Patients whose MPR was 80 percent or greater were considered adherent.
Added Richard Faris, PhD, RPh, National Practice Leader of the Accredo Rare and Specialty Pharmacy Therapeutic Resource Center: "These findings are important because they help in identifying patients experiencing depression while being treated in the home, and enable intervention to drive better outcomes for the patient and reduced costs for the payer."
About Medco
Medco Health Solutions, Inc. (NYSE: MHS) is pioneering the world's most advanced pharmacy® and its clinical research and innovations are part of Medco making medicine smarter™ for approximately 65 million members.
With more than 20,000 employees worldwide dedicated to improving patient health and reducing costs for a wide range of public and private sector clients, and 2010 revenues of nearly $66 billion, Medco ranks 35th on the Fortune 500 list and is named among the world's most innovative, most admired and most trustworthy companies.
For more information, go to http://www.medcohealth.com.
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that may cause results to differ materially from those set forth in the statements. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the risks and uncertainties that affect our business, particularly those mentioned in the Risk Factors section of the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission.
SOURCE Medco Health Solutions, Inc.
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RELATED LINKS
http://www.medcohealth.com
BALTIMORE, April 11, 2011 /PRNewswire/ -- Adherence to interferon, an important medication used to treat Hepatitis C, is critical to successfully clearing the virus that causes the disease. A new observational analysis by Medco Health Solutions, Inc. (NYSE: MHS) finds that when Hepatitis C patients are also being treated for depression -- a frequent side effect of interferon use -- they are more likely to remain on their interferon therapy. The analysis is being presented today at the International Conference on Viral Hepatitis 2011.
According to the study, approximately 40 percent of Hepatitis C patients on interferon and ribavirin -- an antiviral medication used in combination with interferon -- were not adherent to their medication regimen. This puts patients at risk for progression of their disease due to their inability to eliminate the virus. The research found that the patients also using an antidepressant had the highest rates of adherence to their Hepatitis C treatment. Among patients with Hepatitis C who were using an antidepressant, 68.5 percent were adherent to their interferon therapy. For patients being treated for both Hepatitis C and HIV, 77.3 percent taking antidepressants were properly complying with their interferon therapy. Overall, 46 percent of patients with Hepatitis C were on an antidepressant.
"A common side-effect of interferon is depression, but little research has been done looking at the impact of treating depression on a patient's adherence with their Hepatitis C medications," said Mary Cassler RPh, Director of Clinical Innovation in Medco's Advanced Clinical Science and Research Group, who conducted the analysis. "These findings point to the need to proactively screen patients on interferon for depression and make sure that those who show signs of depression receive the proper interventions."
The usual course of interferon therapy for patients with Hepatitis C lasts either 24 or 48 weeks depending on the genotype of the virus, which influences the duration of treatment. Patients who discontinue use of the medication before treatment is completed, or those who do not take their medication as prescribed, frequently need to be retreated. Patients who fail to completely eliminate the virus have a higher risk of developing liver cancer. According to a study published in the American Journal of Managed Care, therapy can cost more than $40,000 per patient.
"Depression, whether interferon-induced or a separate co-morbid condition, can sabotage efforts to effectively treat Hepatitis C," said Dr. David Muzina, National Practice Leader, Medco Neuroscience Therapeutic Resource Center®. "All health care professionals, including pharmacists, need to know how to detect depression and work together to support safe, effective and affordable treatments."
Details
The analysis reviewed de-identified prescription drug claims from Medco's database and identified 3,607 patients who were newly prescribed interferon and ribavirin to treat Hepatitis C. Among the Hepatitis C patients who were identified, only 1,657 were being treated for depression. For the 109 patients who were also co-infected with HIV, 66 were on an antidepressant.
Adherence was evaluated by using the medication possession ratio (MPR) which measures the percent of time that patients have medication available for their use. Patients whose MPR was 80 percent or greater were considered adherent.
Added Richard Faris, PhD, RPh, National Practice Leader of the Accredo Rare and Specialty Pharmacy Therapeutic Resource Center: "These findings are important because they help in identifying patients experiencing depression while being treated in the home, and enable intervention to drive better outcomes for the patient and reduced costs for the payer."
About Medco
Medco Health Solutions, Inc. (NYSE: MHS) is pioneering the world's most advanced pharmacy® and its clinical research and innovations are part of Medco making medicine smarter™ for approximately 65 million members.
With more than 20,000 employees worldwide dedicated to improving patient health and reducing costs for a wide range of public and private sector clients, and 2010 revenues of nearly $66 billion, Medco ranks 35th on the Fortune 500 list and is named among the world's most innovative, most admired and most trustworthy companies.
For more information, go to http://www.medcohealth.com.
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that may cause results to differ materially from those set forth in the statements. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the risks and uncertainties that affect our business, particularly those mentioned in the Risk Factors section of the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission.
SOURCE Medco Health Solutions, Inc.
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RELATED LINKS
http://www.medcohealth.com
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