Here’s VRTX’s own PR on publication of the PROVE-3 study.
The data reported here are almost identical to the data reported
at 2009 EASL (#msg-37316151); the main difference is that one
additional patient in the “breakthrough” subgroup of the “24+24”
arm achieved an SVR, raising the SVR rate for this cohort from
the 50% (4/8) reported at EASL 2009 to 62% (5/8). The above
change also raised the all-subgroup SVR rate in the “24+24”
arm from 52% to 53%. Additionally, this PR shows the results
for the no-ribavirin arm, which were omitted from the 2009
EASL dataset.
http://finance.yahoo.com/news/New-England-Journal-of-bw-299329553.html?x=0&.v=1
›New England Journal of Medicine Publishes PROVE 3 Trial Showing Telaprevir-Based Regimens Significantly Increased Sustained Viral Response (SVR) Rates in Patients Who Did Not Achieve SVR with Prior HCV Therapy
-51% and 53% SVR rates when telaprevir was dosed in combination with pegylated-interferon and ribavirin in treatment-failure patients, compared to 14% SVR rate with pegylated-interferon and ribavirin alone-
-Telaprevir Phase 3 SVR data expected in second quarter 2010 for treatment-naïve patients and third quarter 2010 for treatment-failure patients-
-New Drug Application submission planned for second half of 2010 in treatment-naïve and treatment-failure HCV patients-
Wednesday April 7, 2010, 5:00 pm EDT
CAMBRIDGE, Mass.--(BUSINESS WIRE)--In a clinical trial known as PROVE 3 published in this week’s New England Journal of Medicine, treatment with telaprevir-based regimens significantly increased rates of sustained viral response (SVR) in patients with genotype 1 hepatitis C virus (HCV) infection who did not achieve SVR with at least one prior course of pegylated-interferon and ribavirin therapy. In the trial, 51 percent and 53 percent of patients who received telaprevir in combination with pegylated-interferon and ribavirin as part of a 24-week or 48-week regimen, respectively, achieved SVR. In the control arm, 14 percent of patients achieved SVR. Discontinuation of study drugs because of adverse events was more frequent in patients who received a telaprevir-based regimen than in patients who received only pegylated-interferon and ribavirin. Telaprevir is an investigational oral HCV protease inhibitor being developed by Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) in collaboration with Tibotec and Mitsubishi Tanabe Pharma. A Phase 3 registration program for telaprevir is nearing completion, and Vertex plans to submit a New Drug Application to the U.S. Food and Drug Administration (FDA) for telaprevir in the second half of 2010 for both treatment-naïve and treatment-failure patients.
Chronic HCV infection affects up to 3.9 million individuals in the United States.1 Approximately 40 to 46 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin achieve SVR,2,3,4 or a viral cure. Patients who do not achieve SVR with an initial regimen of pegylated-interferon and ribavirin have a low likelihood of success with re-treatment with pegylated-interferon and ribavirin.5
“More than half our patients with genotype 1 infection don’t respond to pegylated-interferon and ribavirin, and they have a very limited chance of achieving permanent viral eradication when re-treated using currently approved therapies,” said John McHutchison, M.D., Lead Investigator for the PROVE 3 trial and Associate Director of the Duke Clinical Research Institute. “There is, therefore, a clear need for more effective treatment options in these patients. The significantly higher SVR rates observed in the PROVE 3 trial with telaprevir-based regimens represent an important step forward in the potential future treatment of patients who have failed current therapies.”
“More than 50 percent of the treatment-failure patients who received telaprevir in combination with pegylated-interferon and ribavirin in the PROVE 3 trial achieved a sustained viral response – a striking result in this difficult-to-treat patient population,” said Robert Kauffman, M.D., Ph.D., Senior Vice President, Clinical Development and Chief Medical Officer for Vertex. “Based on the PROVE 3 data, as well as clinical data from the PROVE 1 and PROVE 2 trials in treatment-naïve patients published in the New England Journal of Medicine in April 2009, Vertex is currently evaluating telaprevir in a global Phase 3 registration program that enrolled more than 2,200 treatment-failure and treatment-naïve HCV patients. Assuming the trials are successful, we expect to submit an application for approval of telaprevir with the U.S. FDA in the second half of 2010.”
PROVE 3 Trial Results
PROVE 3 was a Phase 2b, randomized, partially double-blind, partially placebo-controlled trial that enrolled and treated 453 genotype 1 HCV patients who did not achieve SVR with a previous regimen of pegylated-interferon (peg-IFN) and ribavirin (RBV) therapy. PROVE 3 consisted of three telaprevir-based treatment arms and one control arm. The trial enrolled patients at 53 international clinical trial sites.
The primary endpoint of the PROVE 3 trial was SVR, defined as the proportion of patients who had no detectable hepatitis C virus in their blood (undetectable plasma HCV RNA) 24 weeks after the completion of therapy. Final SVR results from each arm of the PROVE 3 trial are outlined in the table below:
Final PROVE-3 Arm 1: Arm 2: Arm 3: Arm 4:
SVR Results 12 weeks of 24 weeks of 24 weeks of 48-week
telaprevir, telaprevir, Telaprevir & Control
peg-IFN & RBV peg-IFN & RBV peg-IFN (no Arm of
followed by 12 followed by 24 ribavirin)* peg-IFN
weeks of only weeks of only &RBV
peg-IFN & RBV* peg-IFN & RBV*
Prior Nonresponse1 39% 38% 11% 9%
Prior Relapse2 69% 76% 42% 20%
Prior Breakthrough3 57% 62% 36% 40%
All Patients 51% 53% 24% 14%
* Patients in PROVE 3 received 750mg of telaprevir (or placebo) orally every eight hours, based on treatment arm, and a once-weekly 180ug injection of Peginterferon alfa-2a, as well as a 1,000mg or 1,200mg weight-based daily oral dose of ribavirin.
(1) Non-responders are defined as patients who never achieved undetectable HCV RNA during or at the end of prior therapy. In this trial, 260 patients (260 of 453; 57%) were classified as having prior nonresponse to HCV therapy.
(2) Relapsers are defined as patients who achieved undetectable HCV RNA after prior treatment, but relapsed during follow-up and did not achieve SVR. In this trial, 162 patients (162 of 453; 36%) were classified as having prior relapse to HCV therapy.
(3) Breakthroughs are defined as patients who had undetectable HCV RNA during prior treatment, but had detectable HCV RNA before the end of prior treatment. In this trial, 31 patients (31 of 453; 7%) were classified as having prior breakthrough to HCV therapy.
The SVR rates for the 24-week (arm one) and 48-week (arm two) regimens that included ribavirin were similar. However the relapse rate for the 24-week regimen (arm one) was 30 percent compared to 13 percent in the 48-week regimen (arm two). The relapse rate was 53 percent for the 24-week regimen that did not include ribavirin (arm three) and 53 percent for the control arm.
Together, these data suggest that a 48-week telaprevir-based treatment regimen that includes 12 weeks of telaprevir, pegylated-interferon and ribavirin followed by 36 weeks of only pegylated-interferon and ribavirin may provide treatment-failure patients with an increased likelihood of achieving SVR. A Phase 3 clinical trial known as the REALIZE trial is ongoing in treatment-failure patients, including patients with nonresponse to prior HCV therapy, and is evaluating a 48-week telaprevir-based treatment regimen that contains 12 weeks of telaprevir, pegylated-interferon and ribavirin followed by 36 weeks of only pegylated-interferon and ribavirin.
Patients who did not achieve SVR in the control arm of the PROVE 3 trial, as well as patients who did not achieve SVR in the control arms of the PROVE 1 and PROVE 2 trials, could enroll in Study 107, an open-label rollover trial of telaprevir-based treatment. Results of Study 107 will be presented at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL; The International Liver CongressTM) in Vienna, Austria on April 15, 2010.
Telaprevir Safety & Tolerability in PROVE 3
Several of the most common adverse events in PROVE 3, such as fatigue and influenza-like symptoms, were consistent with typical interferon-related adverse events. The most common adverse events reported more frequently in the telaprevir treatment arms compared to the placebo arms were fatigue, pyrexia, gastrointestinal disorders, pruritus, rash, alopecia, insomnia and anemia. Patients who received a telaprevir-based regimen were more likely to discontinue all treatment because of an adverse event (50 of 339 patients; 15 percent overall), as compared to the control arm (5 of 114 patients; 4 percent overall). Skin disorders were the most common cause of discontinuation in the telaprevir arms (22 of 50 the patients who discontinued because of adverse events), with the majority of these patients discontinuing all treatment because of rash. The overall discontinuation rate due to rash in the telaprevir-based arms was 5 percent (18 of 339 patients).‹
