Showing posts with label SVR. Show all posts
Showing posts with label SVR. Show all posts
Monday, October 15, 2012
Initial Abbott Labs interferon-free triple combination data released...
Posted 10/15/12 on Trust.org. The pre-AASLD press release parade is in full swing!! This time Abbott Labs checks in with some pretty impressive data (although you never know until you see the full abstract/presentation) with it's 3 drug interferon-free combo + ribavirin (HCV protease inhibitor ABT-450, polymerase inhibitor ABT-333 and NS5A inhibitor ABT-267 + RBV). Although the numbers are small, 76 out of 77 treatment naive patients and 38 out of 41 null responders achieved SVR12. I believe, however, it was an Abbott's PILOT study looking at a combo of ABT-450 plus non-nuc ABT-072 and RBV where two patients experienced 'late relapse'... one at week 8 post-treatment and one at week 36. We'll have to see if 'late relapse' is a phenomena with just that certain combination or if a more robust 3 drug combination is enough to quash the virus for a true SVR. I'd also like to see the IL28B genotype and sub-type of this study population, as well as BMI, steatosis and cirrhosis percentages as well. But without the benefit of an in-depth look under the hood, this initial data looks pretty impressive.
Mon, 15 Oct 2012 18:27 GMT
Source: Reuters // Reuters
* 99 pct of untreated patients achieve cure, or SVR, at 12 weeks
* 93 pct of previously unresponsive patients reach SVR at 12 weeks
* Abbott shares rise 3.3 percent (Adds analyst comment, updates shares)
By Bill Berkrot
Oct 15 (Reuters) - An all oral regimen of experimental hepatitis C medicines developed by Abbott Laboratories led to high cure rates in both new patients and those for whom prior treatment failed, according to initial results from a midstage study.
Shares of Abbott rose more than 3 percent after the unveiling of the data, which will be presented next month at a major liver disease meeting. The findings should help cement Abbott as a major player in the race to develop an interferon-free treatment regimen for the serious liver disease.
After 12 weeks of treatment with three Abbott direct-acting antiviral medicines plus the older drug ribavirin, 99 percent of previously untreated patients and 93 percent of those who did not respond to older drugs achieved a sustained virologic response (SVR), which is considered cured, according to available data from a brief summary, or abstract, of the study.
Abbott will present much more detail on the Phase II study involving data from more patients at the American Association for the Study of Liver Diseases (AASLD) meeting in Boston.
"The data looks very good on efficacy and I didn't see anything that really caught my eye as far as side effects," Morningstar analyst Damien Conover said.
Based on the results, Abbott said it would test its three drugs, each of which attacks the virus using a different approach, both with and without ribavirin in a large Phase III program aimed at gaining approval for the treatment.
"The ability to show a sustained virological response in these patient populations without the use of interferon is extremely encouraging," Scott Brun, Abbott's head of infectious disease development, said in a statement.
A pair of new hepatitis C drugs approved last year significantly boosted cure rates and cut treatment duration to as low as 24 weeks for some patients. But those must still be taken with interferon, an injected drug that often causes severe flu-like symptoms that lead many hepatitis patients to delay or discontinue treatment.
Several companies, including Gilead Sciences Inc, Bristol-Myers Squibb Co and Vertex Pharmaceuticals Inc , are racing to develop interferon-free treatment regimens expected to bring in billions of dollars in revenue once approved.
Most analysts view Gilead as current leader both on timing and perceived advantages of its experimental hepatitis C program.
"One of the questions lingering here is whether these (Abbott) drugs can be used without ribavirin," Conover said. "Gilead's drug works pretty well without it, so it's going to be a pretty big competitive hurdle if they have to use ribavirin."
While not as onerous as interferon, ribavirin also has side effects that doctors and patients would like to avoid if possible.
The Abbott drugs, a protease inhibitor called ABT-450, a polymerase inhibitor ABT-333 and ABT-267 from a class known as NS5A inhibitors, were given along with ribavirin for just 12 weeks. Patients in whom the virus was undetectable 12 weeks after stopping treatment were considered cured.
Based on available data at the time the abstract was submitted for the liver meeting, 76 of 77 previously untreated patients and 38 of 41 prior null responders had achieved SVR.
Null responders, while a much smaller market than new patients, have been notoriously difficult to treat.
"The data presented so far appear to be very favorable in these early trials and we'll look for more extensive data at AASLD," JP Morgan analyst Michael Weinstein said in a research note, adding that he expects Abbott's hepatitis C program to reach the market by 2015.
One subject in the new patient group had a disease relapse after treatment and three of the prior null responders experienced viral breakthrough, meaning the virus levels rose during treatment after an initial response.
The most common side effects were fatigue and headache in both groups. Of five reported serious adverse events, one - joint pain - was deemed to be possibly caused by study drugs, the company said.
Abbott shares were up $2.29, or 3.3 percent, at $71.57 at midday on the New York Stock Exchange after rising to a new high of $71.99 earlier. (Reporting by Bill Berkrot; Editing by Andrew Hay, Steve Orlofsky and M.D. Golan)
Wednesday, July 18, 2012
GUT: Vitamin B12 may improve SVR rates in HCV infected patients...
Study posted 7/18/12 via the journal GUT. Researchers in Italy find a link between 5000 ug every 4 weeks of vitamin B12 and improved SVR... especially in the more difficult-to-treat genotype 1 patients with high baseline viral loads. Researchers noted a 34% improvement in SVR in the arms containing B12 than in the arms that didn't. That's pretty cool in my book, but let's do a gut check all the same. OK, it's a small study, it's European (which means the patients have a higher probability of being Caucasian, lower BMI, CC alelle, genotype 1b, all that stuff that makes these patients more likely to respond to traditional pegylated interferon + ribavirin therapy than patient types over here in the States) but hey!! Vitamin B12 can be had on the cheap! Further prospective and larger clinical trials will have to be done to confirm or deny the seemingly extra added boost to SVR rates, especially with the new standard of care. Let's hope it's not another silymarin experience.
GUT
Vitamin B12 supplements may help treat hepatitis C
Safe and inexpensive option for boosting response rate to antiviral drugs
[Vitamin B12 supplementation improves the rate of sustained viral response in patients chronically infected with hepatitis C virus Online First doi 10.1136/gutjnl-2012-302344]
Adding vitamin B12 to standard hepatitis C virus (HCV) treatment significantly boosts the body’s ability to keep the virus at bay, indicates a pilot study published online in the journal Gut.
The effects were particularly strong in patients whose infection was proving difficult to treat effectively, the findings showed.
Between 60% and 80% of those infected with the viral liver infection HCV will go on to develop chronic hepatitis, and roughly a third of them will progress to cirrhosis and terminal liver disease.
Standard treatment of interferon (peg IFN) and ribavarin clears the virus in about 50% of patients infected with genotype 1 HCV and 80% of those infected with genotypes 2 or 3. But this approach fails to clear the virus in around half of all those infected with HCV or the infection returns once treatment stops.
While trials of new generation antiviral drugs show promise, they are expensive, and can make treatment more difficult. And questions still remain about how well they will work in practice, say the authors.
Experimental research dating back a decade suggests that vitamin B12 may have a role in suppressing HCV. The liver is the body’s primary storage centre for vitamin B12, but this capacity is impaired by diseases directly affecting the organ. The researchers therefore wanted to see if adding vitamin B12 to standard treatment would make a difference.
Ninety four patients with HCV infection were randomly allocated to receive standard treatment or standard treatment plus vitamin B12 (5000 ug every 4 weeks) for between 24 (genotypes 2 and 3) and 48 weeks (genotype 1).
The body’s ability to clear the virus was assessed after 4 weeks (rapid viral response), after 12 weeks (complete early viral response), at the end of treatment and at 24 weeks after stopping treatment (sustained viral response).
There was no difference between the two treatment approaches at 4 weeks, but there were significant differences in response at all the other time points, particularly 24 weeks after stopping treatment, which is the aim of HCV treatment and the closest it can be get to a cure.
The effects were also significantly greater among those who carried the type 1 strain, which is particularly hard to treat, and those high levels of infection (high viral load) to begin with.
Overall, adding vitamin B12 to standard therapy strengthened the rate of sustained viral response by 34%, the findings showed.
The authors conclude that until clear eligibility criteria for treatment with the new generation antiviral drugs are established, standard treatment plus vitamin B12 is a safe and inexpensive alternative, particularly for those who carry a strain of the virus that is hard to treat.
They add: “This strategy would be especially useful in those countries where, owing to limited economic means, the new generation antiviral therapies cannot be given in routine practice.”
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.
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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:
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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.
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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, July 7, 2011
Medivir/Tibotec's HCV protease inhibitor TMC435 receives FDA 'Fast-Track' status...
Medivir: TMC435 has Received Fast Track Designation from the FDA and TMC435 will be studied in combination with Pharmasset's PSI-7977 for HCV genotype-1
HUDDINGE, Sweden, Jul 06, 2011 (BUSINESS WIRE) -- Regulatory News:
Medivir AB (sto:MVIRB)(omx:MVIR), is an emerging research-based specialty pharmaceutical company focused on infectious diseases.
Medivir today announced that its investigational protease inhibitor TMC435 has 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 CHC infection compared to currently approved therapies.
TMC435 may offer:
-- High sustained virological response (SVR) rates in genotype-1 HCV-infected patients, including hard-to-treat subgroups
-- Short treatment duration
-- Favorable overall safety and tolerability profile
-- A convenient once-daily (q.d.) dosing regimen
Furthermore, Medivir also confirms the intention to start a proof-of-concept oral, interferon-free phase 2 trial, investigating the combination of TMC435, a once daily NS3/4A protease inhibitor (PI) for the treatment of genotype-1 chronic hepatitis C virus (HCV) infection and Pharmasset's PSI-7977, a once daily nucleotide NS5B polymerase inhibitor. The phase 2 study, which is being managed by Tibotec Pharmaceuticals, will investigate the efficacy and safety of 12 weeks or 24 weeks of TMC435 150 mg q.d. in combination with PSI-7977 400 mg q.d. with or without ribavirin in prior null responders to peginterferon/ribavirin therapy. The primary endpoint of the trial will be sustained virological response at 12 weeks (SVR12).
Bertil Samuelsson, CSO, of Medivir commented, "We are delighted to have received the Fast Track designation for TMC435 from the FDA. This shows that TMC435 with its high safety profile, efficacy, short treatment duration and convenience of once daily dosing is believed to have the potential to provide benefit over current treatments. We believe TMC435 has the potential to become a cornerstone of future direct-acting antiviral combinations for HCV therapy. We are thus very pleased over the clinical collaboration agreement Pharmasset announced today with Tibotec, and the coming start-up of a TMC435 combination trial with Pharmasset's once daily NS5B nucleotide inhibitor PSI-7977. This is one of several ongoing TMC435 combination trials and we expect the momentum to continue with regards to the development of TMC435"
About Fast Track
Fast Track is a process designed to facilitate the development, and expedite the review of drugs to treat serious diseases and to fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious diseases. "Filling an unmet medical need" is defined as providing a therapy where none exists or providing a therapy that may potentially be superior to existing therapy. If there are existing therapies, a fast track drug must show some advantage over available treatment, such as:
-- Showing superior effectiveness
-- Avoiding serious side effects of an available treatment
-- Improving the diagnosis of a serious disease where early diagnosis results in an improved outcome
-- Decreasing a clinically significant toxicity of an accepted treatment
A drug that receives Fast Track designation is eligible for some or all of the following:
-- More frequent meetings with the FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval
-- More frequent written correspondence from the FDA about such things as the design of the proposed clinical trials
-- Eligibility for Accelerated Approval, i.e., approval on an effect on a surrogate or substitute endpoint reasonably likely to predict clinical benefit
-- Rolling Review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by FDA, rather than waiting until every section of the application is completed before the entire application can be reviewed. NDA review usually does not begin until the drug company has submitted the entire application to the FDA
-- Dispute resolution if the drug company is not satisfied with an FDA decision not to grant Fast Track status.
In addition, most drugs that are eligible for Fast Track designation are likely to be considered appropriate to receive a Priority Review.
Once a drug receives Fast Track designation, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.
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 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.
Three global clinical phase 3 response guided studies were initiated in early 2011 by Tibotec:
-- 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
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 US Centers for Disease Control ("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(TM)/Xerclear(R) was launched on the US market in February 2011. Xerese(TM)/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
HUDDINGE, Sweden, Jul 06, 2011 (BUSINESS WIRE) -- Regulatory News:
Medivir AB (sto:MVIRB)(omx:MVIR), is an emerging research-based specialty pharmaceutical company focused on infectious diseases.
Medivir today announced that its investigational protease inhibitor TMC435 has 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 CHC infection compared to currently approved therapies.
TMC435 may offer:
-- High sustained virological response (SVR) rates in genotype-1 HCV-infected patients, including hard-to-treat subgroups
-- Short treatment duration
-- Favorable overall safety and tolerability profile
-- A convenient once-daily (q.d.) dosing regimen
Furthermore, Medivir also confirms the intention to start a proof-of-concept oral, interferon-free phase 2 trial, investigating the combination of TMC435, a once daily NS3/4A protease inhibitor (PI) for the treatment of genotype-1 chronic hepatitis C virus (HCV) infection and Pharmasset's PSI-7977, a once daily nucleotide NS5B polymerase inhibitor. The phase 2 study, which is being managed by Tibotec Pharmaceuticals, will investigate the efficacy and safety of 12 weeks or 24 weeks of TMC435 150 mg q.d. in combination with PSI-7977 400 mg q.d. with or without ribavirin in prior null responders to peginterferon/ribavirin therapy. The primary endpoint of the trial will be sustained virological response at 12 weeks (SVR12).
Bertil Samuelsson, CSO, of Medivir commented, "We are delighted to have received the Fast Track designation for TMC435 from the FDA. This shows that TMC435 with its high safety profile, efficacy, short treatment duration and convenience of once daily dosing is believed to have the potential to provide benefit over current treatments. We believe TMC435 has the potential to become a cornerstone of future direct-acting antiviral combinations for HCV therapy. We are thus very pleased over the clinical collaboration agreement Pharmasset announced today with Tibotec, and the coming start-up of a TMC435 combination trial with Pharmasset's once daily NS5B nucleotide inhibitor PSI-7977. This is one of several ongoing TMC435 combination trials and we expect the momentum to continue with regards to the development of TMC435"
About Fast Track
Fast Track is a process designed to facilitate the development, and expedite the review of drugs to treat serious diseases and to fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious diseases. "Filling an unmet medical need" is defined as providing a therapy where none exists or providing a therapy that may potentially be superior to existing therapy. If there are existing therapies, a fast track drug must show some advantage over available treatment, such as:
-- Showing superior effectiveness
-- Avoiding serious side effects of an available treatment
-- Improving the diagnosis of a serious disease where early diagnosis results in an improved outcome
-- Decreasing a clinically significant toxicity of an accepted treatment
A drug that receives Fast Track designation is eligible for some or all of the following:
-- More frequent meetings with the FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval
-- More frequent written correspondence from the FDA about such things as the design of the proposed clinical trials
-- Eligibility for Accelerated Approval, i.e., approval on an effect on a surrogate or substitute endpoint reasonably likely to predict clinical benefit
-- Rolling Review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by FDA, rather than waiting until every section of the application is completed before the entire application can be reviewed. NDA review usually does not begin until the drug company has submitted the entire application to the FDA
-- Dispute resolution if the drug company is not satisfied with an FDA decision not to grant Fast Track status.
In addition, most drugs that are eligible for Fast Track designation are likely to be considered appropriate to receive a Priority Review.
Once a drug receives Fast Track designation, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.
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 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.
Three global clinical phase 3 response guided studies were initiated in early 2011 by Tibotec:
-- 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
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 US Centers for Disease Control ("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(TM)/Xerclear(R) was launched on the US market in February 2011. Xerese(TM)/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
Wednesday, December 1, 2010
Further info on the GI-5005 HCV vaccine study presented at AASLD... hope for those with the IL28 T/T allele?
Synopsis of the GI-5005 study presented at AASLD 2010. Overall, the numbers for GI-5005 aren't extraordinary, but certainly worth further studies. The true benefit for this vaccine may be how it appears to illicit a T-cell response in patients carrying the T allele of the IL28 gene, which didn't occur when the same patients were given standard of care
By: DIANA MAHONEY, Internal Medicine News Digital Network
12/01/10
BOSTON – A therapeutic vaccine against the hepatitis C virus was associated with a significantly higher sustained virologic response rate when added to standard-of-care treatment, and the findings justify further development of the vaccine, Dr. Paul Pockros reported at the annual meeting of the American Association for the Study of Liver Diseases.
In the proof-of-concept trial, 133 patients infected with hepatitis C virus (HCV) genotype 1 were randomized to either triple therapy comprising the experimental GI-5005 vaccine, which is designed to elicit a T-cell response specific to HCV, along with pegylated interferon alfa-2b plus ribavirin (P/R), or the standard P/R therapy alone.
The primary outcome measure was sustained virologic response (SVR), defined as undetectable HCV RNA at 6 months after treatment, said Dr. Pockros of the Scripps Clinic in La Jolla, Calif.
The 68 patients in the experimental group initially received monotherapy with the vaccine, consisting of five weekly injections followed by two monthly injections for a 12-week lead-in period, before progressing to the standard-of-care P/R treatment and once-monthly injections. The 65 patients in the control group received standard-of-care P/R treatment alone.
In both groups, the treatment duration was 48 weeks for treatment-naive patients and 72 weeks for those who had a poor or partial response to prior P/R treatment, said Dr. Pockros. Patients in whom prior P/R therapy induced no notable decrease in HCV viral load, as well as those in whom prior treatment initially resulted in undetectable HCV RNA followed by a viral rebound, were excluded from the analysis.
Among the study’s treatment-naive patients, 58% of those who received the vaccine achieved SVR, compared with 48% of those who received P/R alone. Among the prior poor and partial responders, the respective SVR rates in the vaccine and control groups were 17% and 5%, Dr. Pockros reported.
"There was a slight benefit in the treatment-naive and nonresponders, [but] this was numerical only and was not statistically significant," he said. However, the overall benefit in the vaccine vs. control groups was statistically significant, with respective SVR rates of 47% and 35%, he noted.
The vaccine strategy appears to be safe. "The most common associated adverse events were mild, transient injection-site reactions," said Dr. Pockros. Additionally, he stated, "the discontinuation rates due to adverse events were comparable [13%] in both the triple-therapy and standard-of-care arms."
Of particular interest, Dr. Pockros noted, was the T-cell response in a subgroup of difficult-to-treat patients receiving the vaccine. Previous studies have suggested that patients carrying the T allele of the IL28 gene are at high risk of treatment failure with the standard interferon-based therapy. The T-cell response in vaccine-treated patients, as measured by interferon-gamma enzyme-linked ImmunoSpot assay, "mimicked what we saw with a virologic response," he said.
"Four of five T/T allele patients had a T-cell response – one did not actually get treated – but none of the patients who received standard of care had a T-cell response."
This finding is consistent with the hypothesis that the GI-5005 vaccine corrects a fundamental deficit in cellular immunity in IL28B T/T genotype patients, he said. Although the findings need to be confirmed in additional studies with larger patient populations, the vaccine will likely be genotype specific, he noted.
Because the immune response is similar to that observed in HCV-infected patients who are able to clear the virus without treatment, future studies will evaluate the efficacy of monotherapy with the vaccine in genotype-specific patients, Dr. Pockros said.
The proof-of-concept study was funded by GlobeImmune, manufacturer of the vaccine. Dr. Pockros disclosed financial relationships with GlobeImmune, Genentech, Vertex, Merck, Gilead, Abbott, Pfizer, Phenomix, Tibotec, Pharmasset, 3RT, Novartis, Johnson & Johnson, Achillon, Regulus, Debio, Zymogenetics, and Human Genome Sciences.
By: DIANA MAHONEY, Internal Medicine News Digital Network
12/01/10
BOSTON – A therapeutic vaccine against the hepatitis C virus was associated with a significantly higher sustained virologic response rate when added to standard-of-care treatment, and the findings justify further development of the vaccine, Dr. Paul Pockros reported at the annual meeting of the American Association for the Study of Liver Diseases.
In the proof-of-concept trial, 133 patients infected with hepatitis C virus (HCV) genotype 1 were randomized to either triple therapy comprising the experimental GI-5005 vaccine, which is designed to elicit a T-cell response specific to HCV, along with pegylated interferon alfa-2b plus ribavirin (P/R), or the standard P/R therapy alone.
The primary outcome measure was sustained virologic response (SVR), defined as undetectable HCV RNA at 6 months after treatment, said Dr. Pockros of the Scripps Clinic in La Jolla, Calif.
The 68 patients in the experimental group initially received monotherapy with the vaccine, consisting of five weekly injections followed by two monthly injections for a 12-week lead-in period, before progressing to the standard-of-care P/R treatment and once-monthly injections. The 65 patients in the control group received standard-of-care P/R treatment alone.
In both groups, the treatment duration was 48 weeks for treatment-naive patients and 72 weeks for those who had a poor or partial response to prior P/R treatment, said Dr. Pockros. Patients in whom prior P/R therapy induced no notable decrease in HCV viral load, as well as those in whom prior treatment initially resulted in undetectable HCV RNA followed by a viral rebound, were excluded from the analysis.
Among the study’s treatment-naive patients, 58% of those who received the vaccine achieved SVR, compared with 48% of those who received P/R alone. Among the prior poor and partial responders, the respective SVR rates in the vaccine and control groups were 17% and 5%, Dr. Pockros reported.
"There was a slight benefit in the treatment-naive and nonresponders, [but] this was numerical only and was not statistically significant," he said. However, the overall benefit in the vaccine vs. control groups was statistically significant, with respective SVR rates of 47% and 35%, he noted.
The vaccine strategy appears to be safe. "The most common associated adverse events were mild, transient injection-site reactions," said Dr. Pockros. Additionally, he stated, "the discontinuation rates due to adverse events were comparable [13%] in both the triple-therapy and standard-of-care arms."
Of particular interest, Dr. Pockros noted, was the T-cell response in a subgroup of difficult-to-treat patients receiving the vaccine. Previous studies have suggested that patients carrying the T allele of the IL28 gene are at high risk of treatment failure with the standard interferon-based therapy. The T-cell response in vaccine-treated patients, as measured by interferon-gamma enzyme-linked ImmunoSpot assay, "mimicked what we saw with a virologic response," he said.
"Four of five T/T allele patients had a T-cell response – one did not actually get treated – but none of the patients who received standard of care had a T-cell response."
This finding is consistent with the hypothesis that the GI-5005 vaccine corrects a fundamental deficit in cellular immunity in IL28B T/T genotype patients, he said. Although the findings need to be confirmed in additional studies with larger patient populations, the vaccine will likely be genotype specific, he noted.
Because the immune response is similar to that observed in HCV-infected patients who are able to clear the virus without treatment, future studies will evaluate the efficacy of monotherapy with the vaccine in genotype-specific patients, Dr. Pockros said.
The proof-of-concept study was funded by GlobeImmune, manufacturer of the vaccine. Dr. Pockros disclosed financial relationships with GlobeImmune, Genentech, Vertex, Merck, Gilead, Abbott, Pfizer, Phenomix, Tibotec, Pharmasset, 3RT, Novartis, Johnson & Johnson, Achillon, Regulus, Debio, Zymogenetics, and Human Genome Sciences.
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