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Direct antiviral therapy for HCV
Currently approved treatments for chronic HCV infection are designed to boost the host's immune response to help eradicate the virus. In contrast, Boceprevir is designed to directly attack the virus by inhibiting protease enzymes that are critical to HCV replication.
Boceprevir added to peginterferon/ribavirin increased SVR rates in chronic HCV patients
HCV Transplant Studies GS-7977 Also Telaprevir & Boceprevir
AASLD-Phase III Analyses on Anemia Management With Victrelis (Boceprevir) Combination Therapy, Including Cirrhotic Patients
FDA Hepatitis Update - Victrelis (boceprevir) labeling update
Boceprevir and personalized medicine in hepatitis C virus infection
Telaprevir, boceprevir offer similar efficacy for most patients with HCV 1
Drug-Drug Interactions Added to Boceprevir Label
Video - Victrelis(boceprevir) - Factors That Predict Response of Patients With Hepatitis C
New developments in the management of hepatitis C virus infection: focus on boceprevir
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FDA Hepatitis Update - Victrelis (boceprevir) label updated for drug-drug interactions
Drug-Drug Interactions Added to Hepatitis C Drug Label
Wednesday, August 15, 2012 22:13 |
New information about interactions between boceprevir and
several other drugs has been added to the prescribing information for the
antiviral drug, the Food and Drug Administration announced Aug. 1.
Boceprevir (Victrelis), a protease inhibitor approved for
treating hepatitis C in 2011, interacts with cyclosporine, tacrolimus (Prograf),
escitalopram (Lexapro), atorvastatin (Lipitor), and pravastatin (Pravachol),
according to the FDA statement.
The new information states that, when administered with
boceprevir, exposure to atorvastatin increases. When the two drugs are used
together, the lowest effective dose of atorvastatin should be used, not to
exceed a daily dose of 40 mg, according to the FDA.
Dose adjustments of cyclosporine should be anticipated
when it is given with boceprevir, and should be guided by close monitoring of
cyclosporine blood concentrations, and frequent assessments of renal function
and cyclosporine-related side effects.
When administered with boceprevir, exposure of
escitalopram was slightly decreased, the statement said. Although selective
serotonin reuptake inhibitors (SSRIs) such as escitalopram have a wide
therapeutic index, it may be necessary to adjust the dosage when it is
administered with boceprevir.
Coadministration of boceprevir with pravastatin increases
exposure to pravastatin, but pravastatin can be started at the recommended
dosage when coadministered with boceprevir. Close clinical monitoring is
warranted, the statement said.
Giving tacrolimus and boceprevir together requires
significant dose reduction and prolongation of the dosing interval for
tacrolimus, with close monitoring of tacrolimus blood concentrations and
frequent assessments of renal function and tacrolimus-related side effects, the
Boceprevir is manufactured in a capsule formulation by
Merck Sharp amp; Dohme Corp., a subsidiary of Merck amp; Co., and is taken by
mouth three times a day.
The drug-drug interaction data are from in vivo drug
interaction trials, which the company conducted as part of its postmarketing
At a meeting in April 2011, an FDA advisory panel
enthusiastically supported the approval of boceprevir for treating hepatitis C
infection because of the antiviral?s efficacy but emphasized that postmarketing
studies on interactions with other drugs, including antidepressants, were
Serious adverse events associated with boceprevir should
be reported to MedWatch or by phone at 800-332-1088.
Adding Boceprevir to Hepatitis C Therapy Deemed Practice-Changer
2012 May 22. doi: 10.1002/hep.25865. [Epub ahead of print]
Refinement of stopping rules during treatment of hepatitis C genotype 1 infection with boceprevir
Jacobson IM, Marcellin P, Zeuzem S, Sulkowski MS, Esteban R, Poordad F, Bruno S, Burroughs MH, Pedicone LD, Boparai N, Deng W, Dinubile MJ, Gottesdiener KM, Brass CA, Albrecht JK, Bronowicki JP.
Center for the Study of Hepatitis C, Weill Cornell Medical College, New York, NY.
In comparison with peginterferon/ribavirin alone, boceprevir with peginterferon/ribavirin significantly improves sustained virological response (SVR) rates in patients with chronic hepatitis C virus (HCV) genotype 1 infections, but treatment failure remains a significant problem. Using phase 3 trial databases, we sought to develop stopping rules for patients destined to fail boceprevir-based combination therapy in order to minimize drug toxicity, resistance, and costs in the face of ultimate futility.
Exploratory post hoc analyses using data from the Serine Protease Inhibitor Therapy 2 (SPRINT-2) study (treatment-naive patients) and the Retreatment With HCV Serine Protease Inhibitor Boceprevir and Pegintron/Rebetol 2 (RESPOND-2) study (treatment-experienced patients) were undertaken to determine whether protocol-specified stopping rules (detectable HCV RNA at week 24 for SPRINT-2 and at week 12 for RESPOND-2) could be refined and harmonized. In SPRINT-2, a week 12 rule with an HCV RNA cutoff of ≥100 IU/mL would have discontinued therapy in 65 of 195 failures (sensitivity = 33%) without sacrificing a single SVR among 475 successes (specificity = 100%). Viral variants emerged after week 12 in 36 of the 49 evaluable patients (73%) who would have discontinued at week 12 using a ≥100 IU/mL stopping rule.
In RESPOND-2, five of six patients with week 12 HCV RNA levels between the lower limit of detection (9.3 IU/mL) and the lower limit of quantification (25 IU/mL) who continued therapy despite the protocol-stipulated futility rule achieved SVR; one additional patient with a week 12 HCV RNA level of 148 IU/mL also continued therapy, had undetectable HCV RNA at week 16, and attained SVR.
Conclusion: Although a stopping rule of detectable HCV RNA at week 12 would have forfeited some SVR cases, week
12 HCV RNA levels ≥100 IU/mL almost universally predicted a failure to achieve SVR in both treatment-naive and treatment-experienced patients. In boceprevir recipients, the combination of 2 stopping rules-an HCV RNA level ≥100 IU/mL at week 12 and detectable HCV RNA at week 24-maximized the early discontinuation of futile therapy and minimized premature treatment discontinuation. (HEPATOLOGY 2012).
Copyright © 2012 American Association for the Study of Liver
ITPA Deficiency Cuts Anemia Risk, Even on Boceprevir
Boceprevir in Chronic Hepatitis C Infection
Updated information on drug interactions between Victrelis (boceprevir) and certain boosted HIV protease inhibitor drugs
NICE has given its final recommendation for two new hepatitis C pills in an expedited review.
Boceprevir in Combination With Ritonavir-boosted HIV Protease Inhibitors May Reduce Efficacy of Both, FDA Warns
Boceprevir, Interferon Alfa-2a, Ribavirin Effective in HCV
Boceprevir a useful option for patients who did not respond to earlier course of hepatitis C therapy
Victrelis (boceprevir)-B.C. expands PharmaCare coverage for Hepatitis C
VICTORIA - The Province is expanding PharmaCare coverage for patients suffering from hepatitis C to include the drug boceprevir (Victrelis and Victrelis Triple), helping patients and their families.
Boceprevir was approved by Health Canada for use in patients with chronic hepatitis C in July 2011. Following that approval, the drug was reviewed through the national and provincial drug review processes, which determine if a drug provides benefit over existing drug therapies. The Province undertook an expedited review process, to allow patients who could benefit from boceprevir to access the drug through PharmaCare as quickly as possible.
Victrelis-Merck's hepatitis C drug wins UK cost endorsement
(Reuters) - U.S. drugmaker Merck & Co's new hepatitis C drug Victrelis was recommended for use within Britain's state health service on Friday, despite its hefty price tag.
Hepatitis C Drug Victrelis-Boceprevir released for public use in Australia.
New HCV Clinical Trial To Evaluate Merck’s-VICTRELIS with Roche's Mericitabine Plus SOC
Merck Announces Initiation of Clinical Development Collaboration with Roche To Evaluate Investigational Combination Regimens for the Treatment of Chronic Hepatitis C Genotype 1 Infection
The first trial is designed to provide clinical data on the use of VICTRELIS (boceprevir), an oral HCV NS3/4A protease inhibitor, in combination with mericitabine (RO5024048), Roche's investigational oral HCV NS5B nucleoside polymerase inhibitor, Pegasys® (pegylated interferon alfa-2a) and Copegus® (ribavirin), in adult patients with chronic HCV genotype 1 infection who had a null response to prior peginterferon alfa and ribavirin therapy (less than a 2 log HCV-RNA decline at treatment week 12). The Phase II study, called DYNAMO 1, plans to recruit patients at 25 sites globally.
Boceprevir: Indication of added benefit for specific patients-extent of added benefit still unclear
Some patients with chronic hepatitis C may benefit from boceprevir -- extent of added benefit still unclear
The active ingredient boceprevir has been available since the middle of 2011 as a treatment for chronic hepatitis C of genotype 1. In an early benefit assessment pursuant to the "Act on the Reform of the Market for Medicinal Products" (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) has now examined to establish whether boceprevir offers added benefit in comparison with the previous standard therapy. According to this assessment, the dossier submitted by the pharmaceutical company provides indications of added benefit for patients who have not yet developed liver cirrhosis. However, the extent of this added benefit cannot be classified.
Boceprevir Often Successful as Rescue Treatment in HCV
This coverage is not sanctioned by, nor a part of, the American Association for the Study of Liver Diseases.
November 30, 2011 (San Francisco, California) — Patients with hepatitis C virus (HCV) infection who previously failed combination treatment with pegylated interferon alfa-2a (peginterferon) and ribavirin achieved up to a 50% sustained viral response (SVR) with the recently approved protease inhibitor boceprevir. This finding, from the preliminary results of the ongoing PROVIDE study, was reported here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting.
"This study was designed to give boceprevir treatment to patients who were null responders in the control arms of our previous pivotal trials," said Michelle Treitel, PhD, from Merck Research Laboratories in Kenilworth, New Jersey.
Patients were rolled over from the SPRINT-1, SPRINT-2, RESPOND-2, and PEG 2a/BOC studies into PROVIDE. "These are patients who had either met the futility rule or who had relapsed after the end of treatment with peginterferon and ribavirin. After failure, they were immediately started on 44 weeks of boceprevir/peginterferon/ribavirin triple therapy." The aim of the study was to assess SVR after boceprevir, peginterferon, and ribavirin treatment in nonresponders.
Overall, 168 patients from the 4 studies were enrolled in PROVIDE. Patients were eligible if they received 12 or more weeks of peginterferon plus ribavirin treatment and failed to achieve a SVR (HCV RNA levels below the lower limit of detection of +9.3 IU/mL at treatment week 12 in treatment-experienced patients or at treatment week 24 in treatment-naïve patients), had a virologic breakthrough, or relapsed after the end of treatment (undetectable HCV RNA at the end of treatment but no SVR).
The subanalysis presented by Dr. Treitel involved 48 patients from the SPRINT-2 and RESPOND trials.
Patients were treated with boceprevir 800 mg orally twice daily, peginterferon 1.5 µg/kg subcutaneously once daily, and ribavirin 600 to 1400 mg/day (based on weight) orally in 2 divided doses. All patients received 4 weeks of peginterferon plus ribavirin induction therapy prior to receiving boceprevir. Patients received the boceprevir, peginterferon, ribavirin combination for up to 44 weeks, and were followed for an additional 24 weeks to determine SVR.
The PROVIDE cohort was 64.6% male, 68.8% white, had mean age of 51.0 years, and had a mean body mass index of 26.8 kg/m². Among the patients, 87.5% had a baseline viral load greater than 800,000 IU/mL, 64.6% were infected with HCV genotype 1a, and 4.2% had detectable cirrhosis.
The primary end point of PROVIDE was undetectable HCV RNA 24 weeks after therapy.
In this nonresponder subpopulation, 38% of patients treated with the triple combination achieved a SVR. The achievement of SVR differed by race (27% of black subjects and 42% of nonblack subjects), age (50% of those younger than 50 years and 29% of those older than 50 years), alanine transaminase levels (50% of those with normal levels and 34% of those with elevated levels), and genotype (41% of those infected with genotype 1a and 33% of those with genotype 1b).
"The difference by genotype is the reverse of what you would expect," said Dr. Treitel. "That most likely has to do with the small sample size."
The magnitude of decline in HCV RNA after 4 weeks of peginterferon plus ribavirin induction therapy was positively related to the rate of SVR. Dr. Treitel reported a 50% SVR for patients who experienced a reduction of at least 1 log in HCV RNA, compared with 34% SVR for patients who experienced a reduction of less than 1 log.
"This null group has not been specifically studied for boceprevir before, and these patients are really poor interferon responders," said Dr. Treitel. "In these traditionally very hard-to-treat subjects, we're still showing that you can get a 38% SVR."
Taking It to the Street
"I was very interested to see the rate of response to triple therapy in patients who have previously failed treatment or who were nonresponders," said Abu Hamour, MBBS, MSc, FRCP, from the University Hospital of Northern British Columbia in Prince George, Canada.
The lack of patients with cirrhosis in the study was a sticking point for Dr. Hamour. Although this does not reflect the population of patients he sees in his practice, the conclusions give him something valuable to take home.
"I have this information that I can give to my patients — a prognosis," he said. After treatment with this triple therapy, I can tell patients "who failed treatment with peginterferon/ribavirin or who were nonresponders...[that] if you have a more than a 1 log drop, you have a 50% chance of response; if you have less than a 1 log drop, then your response is much lower, around 35%. Patients can then make choices based on that information."
Dr. Treitel is an employee of Merck Research Laboratory. Dr. Hamour has disclosed no relevant financial relationships.
The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 931. Presented November 7, 2011.
Ontario first province to reimburse new chronic hepatitis C treatment VICTRELIS™ Now Available for Eligible Patients in Ontario
MONTREAL, - Ontarians living with chronic hepatitis C now have publicly funded access to a new treatment option, as Ontario becomes the first province to reimburse VICTRELIS™ (boceprevir). The treatment qualified for a pre-approval rapid review under the Ontario Drug Benefit Act (ODBA), as it successfully met a pre-determined set of criteria, including offering substantial improvements of significant outcomes for the treatment of a serious disease.
Boceprevir is a first-in-class oral hepatitis C virus (HCV) protease inhibitor for the treatment of chronic hepatitis C genotype 1 infection. It is to be used in combination with peginterferon alpha and ribavirin (peg/riba) in adult patients (18 years and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous therapy.2 When added to peg/riba, boceprevir can significantly increase a patient’s chance of clearing the virus from the body.3,4 The treatment was authorized for use in Canada in July of this year.
“The Canadian Liver Foundation is pleased that Ontario’s public drug program has agreed to reimburse boceprevir for the treatment of chronic hepatitis C,” says Dr. Morris Sherman, Chairman of the Canadian Liver Foundation. “Boceprevir represents a major advance in our ability to cure this disease, and as a result, fewer patients will have to struggle with the consequences of end-stage liver disease, liver transplants and liver cancer. We applaud the research efforts that led to this breakthrough and hope other provinces will follow Ontario’s lead and rapidly reimburse this important treatment.”
Eligibility criteria for boceprevir can be accessed through the following link:
Interim Phase IIb Data for Merck's VICTRELIS™ (boceprevir) in Patients Coinfected with Chronic Hepatitis C and HIV-1 Helping People Get VICTRELIS™ (boceprevir)
'Victrelis'®? (boceprevir), first licensed drug to target the hepatitis C virus directly, accepted for use within NHS Scotland for chronic hepatitis C genotype
'Victrelis'®? (boceprevir), first licensed drug to target the hepatitis C virus directly, accepted for use within NHS Scotland for chronic hepatitis C genotype 1
New treatment helps clear the virus in significantly more patients compared to current standard of care alone1A
AASLD-New Data Analyses for VICTRELIS™ (boceprevir) will be Presented By Merck
Treatment of Hepatitis C Iran Review-Boceprevir-Victrelis
New Hepatitis C Drugs Offer Options but With Added Complications
New hepatitis C drug exciting -- but expensive
CTV News.ca Staff
Date: Friday Aug. 5, 2011 2:43 PM ET
Excerpt...Read Full Article Here
A new drug has just been approved by Health Canada for hepatitis C that might put the word "cure" within reach of some patients -- something unheard of with current treatments. But the drug comes with a hefty price tag and it's unclear who will be paying for it. .....
But a new generation of hepatitis drugs is on the horizon. Earlier this week, a new medication called Victrelis (boceprevir) was approved in Canada, designed to be taken in combination with the current hep C therapies....
So far, the provinces haven't said whether they will be covering the medication under provincial health plans. Victrelis is yet another drug to add to the list of ever more costly medications that provinces are being asked to cover.
Infectious diseases expert Dr. Neil Rau admits it's a dilemma....
"The great thing here is that we have a treatment that increases the chance of response, or cure, but if one third of all people with hep C in Canada -- 100,000 people -- got that treatment, that would be 100,000 times $50,000 per person. That's a lot of money," he notes....
Robinson says he's holding out hope that his provincial government will help him. He says he was willing to gamble because he has an 11-year-old and wants to live to see him grow up.
"This is for life or death. Without this, I am dead," he says.....
Boceprevir-Victrelis-Telaprevir "INCIVEK" Which pegylated interferon ?
Aug 3- Health Canada Clears Victrelis-Boceprevir New Hepatitis C Drug
VANCOUVER — A new drug, recently approved by Health Canada, brings a cure closer for the 250,000 hepatitis C sufferers across Canada.
Boceprevir — brand name victrelis — when added to current standard therapy has been shown to have higher cure rates in studies published early this year by the New England Journal of Medicine.
A similar drug, telaprevir, is under 'priority review' at Health Canada.
"Given the prevalence of the disease, this is a significant development" said Dr. Alnoor Ramji, clinical assistant professor at the University of British Columbia. "The new medicine is part of a new generation of drugs that offer patients a greater hope for a cure."
MSD launches hepatitis C drug Victrelis-Boceprevir in UK
MSD (known as Merck in the US and Canada), today launched Victrelis (boceprevir) in the UK. The drug is a new treatment for chronic hepatitis C genotype 1 in adults with compensated liver disease who have yet to undergo treatment or have failed previous therapy.
Victrelis is the first licensed treatment for hepatitis C which is direct acting, targeting the virus itself. The launch follows an accelerated assessment by the European Medicines Agency (EMA), due to its "major public-health need."
In comparison to current therapies, Victrelis works through inhibiting a key viral enzyme, affecting the virus' ability to replicate.
Victrelis is to be used in combination with the current standard treatment to tackle genotype 1 of the virus, the most prominent strand in the UK, affecting 40-50 per cent of patients.
In clinical trials of those who had previously failed treatment, the addition of Victrelis to standard therapy almost tripled the number of patients clearing the virus.
Boceprevir response and resistance differs according to HCV genotype 1 subtype
VICTRELIS™ (boceprevir), Approved in the European Union for Treatment of Chronic Hepatitis C
VICTRELIS™- Boceprevir: Prescribing Information and Medication Guide
Merck has included Victrelis/Boceprevir to its patient assistance program/May 22
Getting Ready; Telaprevir or Boceprevir ?
Understanding Your Viral Load
BOCEPREVIR FDA APPROVED !
Vicrelis/Boceprevir IS NOW FDA Approved May 13 2011
SILVER SPRING, Md., May 13, 2011 /PRNewswire-USNewswire/ -- The U.S. Food and Drug Administration today approved Victrelis (boceprevir) to treat certain adults with chronic hepatitis C. Victrelis is used for patients who still have some liver function, and who either have not been previously treated with drug therapy for their hepatitis C or who have failed such treatment. Victrelis is approved for use in combination with peginterferon alfa and ribavirin.
The safety and effectiveness of Victrelis was evaluated in two phase 3 clinical trials with 1,500 adult patients. In both trials, two-thirds of patients receiving Victrelis in combination with pegylated interferon and ribavirin experienced a significantly increased sustained virologic response (i.e., the hepatitis C virus was no longer detected in the blood 24 weeks after stopping treatment), compared to pegylated interferon and ribavirin alone, the current standard of care.
When a person sustains a virologic response after completing treatment, this suggests that HCV infection has been cured.
Sustained virologic response can result in decreased cirrhosis and complications of liver disease, decreased rates of liver cancer (hepatocelluar carcinoma), and decreased mortality.
"Victrelis is an important new advance for patients with hepatitis C," said Edward Cox, M.D., M.P.H, director, Office of Antimicrobial Products in FDA's Center for Drug Evaluation and Research. "This new medication provides an effective treatment for a serious disease, and offers a greater chance of cure for some patients' hepatitis C infection compared to currently available therapy."
According to the U.S. Centers for Disease Control and Prevention, about 3.2 million people in the United States have chronic hepatitis C, a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure.
Most people with hepatitis have no symptoms of the disease until liver damage occurs, which may take several years.
Most liver transplants performed in the United States are due to progressive liver disease caused by hepatitis C virus infection. After the initial infection with hepatitis C virus (HCV), most people develop chronic hepatitis C. Some will develop cirrhosis of the liver over many years. Cirrhosis can lead to liver damage with complications such as bleeding, jaundice (yellowish eyes or skin), fluid accumulation in abdomen, infections, or liver cancer.
People can get the hepatitis C virus in a number of ways, including: exposure to blood that is infected with the virus; being born to a mother with HCV; sharing a needle; having sex with an infected person; sharing personal items such as a razor, toothbrush with someone who is infected with the virus, or from unsterilized tattoo or piercing tools.
Victrelis is a pill taken three times a day with food. The therapy is part of a class of drugs referred to as protease inhibitors, which work by binding to the virus and preventing it from multiplying.
The most commonly reported side effects in patients receiving Victrelis in combination with pegylated interferon and ribavirin include fatigue, low red blood cell count (anemia), nausea, headache and taste distortion (dysgeusia).
Victrelis is marketed by Whitehouse Station, N.J.-based Merck.
For more information:
FDA: Approved Drugs: Questions and Answers
FDA: What's New at FDA in Hepatitis
FDA: Hepatitis C Tests
CDC: Hepatitis C Information for the Public
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Media Inquiries: Erica Jefferson, 301-796-4988, email@example.com
Consumer Inquiries: 888-INFO-FDA
SOURCE U.S. Food and Drug Administration
The drug company Merck announced they're ready to launch Boceprevir in May, depending on FDA approval. Both telaprevir and boceprevir have been recommended by the advisory community for the treatment of hepatitis C.
FDA Panel Endorses Boceprevir for Hepatitis C
4/27/2011 MedPage Today Gastroenterology
(MedPage Today) -- SILVER SPRING, Md. -- An FDA advisory committee has voted unanimously to recommend approval of the investigational drug boceprevir (Victrelis), in combination with peginterferon and ribavirin, to treat hepatitis C
The News Today Is All About Boceprevir
March 31 2011; From the
New England Journal of Medicine.
Boceprevir for Untreated Chronic HCV Genotype 1 Infection
F. Poordad and Others
Boceprevir for Previously Treated Chronic HCV Genotype 1 Infection
B.R. Bacon and Others
A Better Way to Unbind Prometheus? Boceprevir for the Treatment of Chronic Hepatitis C Infection
Boceprevir; Difficult Hepatitis C Type Responds to Novel Protease Inhibitor
Research Fuels Hope for Hard-To-Treat Hepatitis C Patients
Released: 12/6/2010 12:00 PM EST
Source: Saint Louis University Medical Center
Newswise — The outlook for patients with hepatitis C continues to improve as results from a clinical trial led by a Saint Louis University researcher found that the drug boceprevir helped cure hard-to-treat patients. The findings were reported at the 61st annual meeting of the American Association for the Study of Liver Disease’s earlier in November.
Bruce R. Bacon, M.D., professor of internal medicine at Saint Louis University School of Medicine and co-principal investigator of the HCV RESPOND-2 study, studied the protease inhibitor, boceprevir, and found that it significantly increased the number of patients whose blood had undetectable levels of the virus Continue Reading.......Research Fuels Hope for Hard-To-Treat Hepatitis C Patients
Hepatitis C/HBV Audio/PIs Boceprevir/Telaprevir/New Nucleosides,Nonnucleosides
AASLD:Telaprevir/Boceprevir/Similar Cure Rates/Shorter Treatment Duration/Boceprevir Achieved
Significantly Higher SVR Rates In Treatment-Failure And Treatment-Naïve Adult Patients With Chronic Hepatitis C Genotype 1 Compare
Oct 30 2010
Video Update on Boceprevir
Top Line Phase III Results: Boceprevir
Boceprevir Meets Primary Endpoints In Two Phase III Studies: Merck
Merck’s two pivotal Phase III registration studies for Boceprevir, its investigational oral hepatitis C protease inhibitor, have been completed and met the primary endpoints. Merck said that the primary endpoints in both studies in patients with chronic hepatitis C virus (HCV) genotype 1 infection, the addition of Boceprevir to treatment with Pegintron (peginterferon alfa-2b) and Rebetol (ribavirin, USP) (Peg/riba) increased the number of patients who achieved sustained virologic response (SVR; defined as undetectable virus levels 24 weeks after the end of treatment), compared to control groups that received Peg/riba plus placebo.
Merck stated that Boceprevir, in combination with Peg/riba, is being studied for the treatment of patients with chronic hepatitis C genotype I who have previously been treated (treatment-failure; HCV RESPOND-2) and in patients who are new to treatment (treatment-naïve; HCV SPRINT-2).
Merck is expected to submit a new drug application (NDA) for Boceprevir to the FDA on a rolling basis, and expects to complete regulatory submissions in the US and EU in 2010.
Peter Kim, president of research laboratories at Merck, said: "We look forward to seeking regulatory approvals to bring Boceprevir forward to treat people living with chronic hepatitis C."
Bruce Bacon, professor of internal medicine at Saint Louis University School of Medicine, and co-principal investigator of the HCV RESPOND-2 study, said: “Patients who failed prior hepatitis C therapy are among the hardest to treat, and the use of Boceprevir in this study helped more of these patients achieve undetectable levels of the virus at 24 weeks after the end of therapy than treatment with Peg/riba alone."
Boceprevir Boosts Hepatitis C Treatment Success Up to 75% Viral Cure Rate When Boceprevir Added to Standard Therapy
By 66% had an SVR with boceprevir plus standard treatment for 48 weeks. Daniel J. DeNoon
WebMD Health News
Boceprevir Clinical Trial Results The boceprevir studies tested the drug in patients with genotype 1 HCV infection. Genotype 1 is the most common HCV strain in the U.S. and is generally considered the most resistant to treatment.
In a phase III clinical trial reported by Merck, among never-before-treated patients:
- 63% had an SVR after four weeks of standard therapy and 44 weeks of boceprevir plus standard therapy.
- 38% on standard treatment had an SVR.
- 66% had an SVR with boceprevir plus standard treatment for 48 weeks.
- 59% had an SVR after four weeks of standard therapy and 44 weeks of boceprevir plus standard therapy.
- 21% on standard treatment had an SVR.
HCV Protease Inhibitor Boceprevir Demonstrates Durable Sustained Response with No Late Relapse
SUMMARY: Genotype 1 chronic hepatitis C patients treated with the Merck/Schering-Plough's investigational NS3 HCV protease inhibitor boceprevir plus pegylated interferon (with or without ribavirin) achieved durable sustained response with no evidence of viral rebound or adverse events lingering after completion of therapy, according to a late-breaker poster presented this week at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010) in Vienna.
From Medscape Medical News Boceprevir Hepatitis C Patients Continue to Fare Well, Data Show Thomas R. Collins
Authors and Disclosures
April 19, 2010 (Vienna, Austria) — Additional encouraging results for boceprevir, an investigational oral protease inhibitor for the treatment of hepatitis C virus (HCV), were unveiled here at the European Association for the Study of the Liver (EASL) 45th Annual Meeting. New data showed that patients with sustained virologic response (SVR) rates continued to have SVR after 2 years of follow-up.
Also, no serious adverse events (SAEs) have emerged since the initial 24-week study period of the Serine Protease Inhibitor Therapy 1 (SPRINT-1) study, according to data reported at the EASL meeting.
New results, however, showed that some mutations were slow in reverting to wild-type virus.
The drug — developed by Schering-Plough, which merged with Merck in November 2009 — is now in a fully enrolled phase 3 trial. Merck officials expect to file the Food and Drug Administration application later this year, and they hope for approval in 2011.
Merck officials hope the new results only bolster their case.
"They did give some signals a few years ago that they would look favorably upon fast-tracking this," said John Vierling, MD, chief of hepatology at the Baylor College of Medicine, Houston, Texas, who worked on the study.
"Is the SVR still defined the same; is it durable? Here it’s durable," Dr. Vierling said. "Was there any latent SAE? The answer to that was no....These are new drugs. And we know the on-treatment responses and we know information about SVR, but making sure there’s not a latent capacity of these to have done any harm I think is an important safety aspect."
Results of the SPRINT-1 study unveiled last year at the EASLmeetingincluded the best SVR rates ever reported for HCV genotype 1 patients.
Those taking peginterferon alfa-2b (1.5 μg/kg once weekly) and ribavirin (800 – 1400 mg/daily, dosed by weight) followed by boceprevir (800 mg 3 times a day) achieved an SVR rate of 75%, almost double the nonboceprevir control group’s rate.
In the new study, researchers followed up those who did and did not achieve SVR in the SPRINT-1 study and followed up nonresponders from 2 other, smaller studies.
They found that none of the patients who had achieved SVR after 24 weeks in the SPRINT-1 study had relapsed compared with 21 patients from another study.
One of the 290 SPRINT-1 study patients was reinfected because of a new mutation that emerged. Researchers did not consider this a relapse.
Dr. Vierling's team also tracked the reversion to wild-type virus for those who had had mutations. They found 91% of those with the V36M mutation reverted, compared with lower reversion rates for types R155K and T54, which reverted to wild type at rates of 71% and 62%, respectively.
Mark Thursz, MD, at Imperial College London in England and vice secretary of EASL, said the SVR data and SAE data were not unexpected, going by previous findings on boceprevir.
"It’s not the most exciting [data], but it’s still interesting," he said.
He said the slow-to-revert nature of the mutations was troubling.
"What was worrying with that was how slowly they go back to the wild type and the fact that a few months after you’ve withdrawn the therapy you can still detect mutations which confer resistance," Dr. Thursz said. "The implication of this is we should not be using these protease inhibitors inappropriately.
"We have to be really sure that once you start that therapy you’re going to clear the virus so you give the patient the best chance that they’re going to clear the virus. Otherwise, you’re inducing mutations by inappropriate use, which may compromise future therapies with protease-targeting drugs," Dr. Thursz cautioned.
The study received commercial support from Merck & Co. Dr. Vierling was an investigator on the study. Dr. Thursz has disclosed no relevant financial relationships.
The European Association for the Study of the Liver (EASL) 45th Annual Meeting. Presented April 15-17, 2010.