Biotech Values

[DewDiligence]

Here’s VRTX’s PROVE-3 PR. The interim data include
SVR12––but not SVR––for the Telaprevir arm, and EoT
data (no SVR12 or SVR) for the control arm. Although
these data look very good, SVR12 is a weaker predictor
of SVR in patients with prior treatment failures than it
is in treatment-naïve patients, and hence it is too soon to
say what SVR is likely to be based on the data in this PR.
Typically, patients who do not achieve RVR
(undetectable virus at 4 weeks) are unlikely to achieve
SVR, and RVR data are notably omitted from this PR!

The table below breaks down the data according to
whether a patient had a non-response (hardest to retreat),
relapse (intermediate), or viral breakthrough (easiest to
retreat) in the first-line setting.

(Please see #msg-26290780 for my opinion on how good
the SVR data from PROVE-3 need to be in order to give
VRTX a chance at FDA approval in this setting without
waiting for data from phase-3.)

http://biz.yahoo.com/bw/080609/20080609005508.html

>>
Vertex Reports 52% SVR12 Rate for 24-week Telaprevir-based Regimen in Genotype-1 Hepatitis C Patients Who Failed Prior Treatment

Monday June 9, 7:30 am ET

-- 73% of prior relapsers achieved SVR12 with 24-week telaprevir-based treatment

-- 41% of prior non-responders achieved SVR12 with 24-week telaprevir-based regimen

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX ) today announced positive results from a planned interim analysis of PROVE 3, an ongoing Phase 2b study evaluating telaprevir-based treatment in patients with genotype 1 chronic hepatitis C virus (HCV) infection who did not achieve sustained virologic response (SVR) with at least one prior pegylated interferon (peg-IFN) and ribavirin (RBV) regimen. Vertex is developing telaprevir in collaboration with Tibotec.

n the interim analysis, 52% (60 of 115; intent-to-treat analysis) of patients randomized to receive treatment with a 24-week telaprevir-based regimen (12 weeks of telaprevir in combination with peg-IFN and RBV, followed by 12 weeks of peg-IFN and RBV alone) maintained undetectable HCV RNA 12 weeks post-treatment (SVR 12). In the interim analysis, adverse events were similar to those commonly observed with peg-IFN and RBV including fatigue, nausea, rash, headache, gastrointestinal disorders and anemia, and were consistent with those previously reported in patients being treated with telaprevir-based therapy in the PROVE 1 and 2 studies in treatment-naïve subjects.

Based on these data, Vertex and Tibotec plan to initiate a Phase 3 clinical trial in patients who have failed prior treatment with peg-IFN and RBV. Telaprevir (TVR) is the most advanced HCV protease inhibitor in clinical development targeting treatment of chronic hepatitis C, and is in Phase 3 clinical development in treatment-naïve patients. Hepatitis C is a disease that afflicts more than 3 million people in the United States alone, and 170 million worldwide.

Interim Analysis Results

PROVE 3 is a randomized, double-blind, placebo-controlled Phase 2b study that enrolled patients who failed prior treatment with peg-IFN and RBV. Patients enrolled in PROVE 3 included prior non-responders (including null responders), prior relapsers and prior breakthroughs to peg-IFN and RBV treatment. The interim analysis included 453 patients that were enrolled and received at least one dose of study drug. In the interim analysis, 52% (60 of 115) of patients randomized to receive a 24-week telaprevir-based regimen (12 weeks of telaprevir in combination with peg-IFN and RBV, followed by 12 weeks of peg-IFN and RBV alone) achieved undetectable HCV RNA (<10 IU/mL; Roche TaqMan) 12 weeks post-treatment (SVR12). Of the 115 patients, 66 were categorized as non-responders to prior treatment (defined as patients who never achieved undetectable HCV RNA during prior treatment, including null responders), 40 were prior relapsers (defined as patients who had undetectable HCV RNA at the completion of prior treatment, but relapsed during follow-up), and 9 were prior breakthroughs (defined as patients who had viral rebound during prior treatment). Among patients receiving the 24-week telaprevir-based regimen, 41% (27 of 66) of the prior non-responders, 73% (29 of 40) of prior relapsers, and 44% (4 of 9) of prior breakthroughs achieved SVR 12.

“Patients who have not achieved a sustained virologic response with one or more courses of prior interferon-based therapy represent a significant unmet medical need. These patients have few or no available treatment options and they are at increased risk for progressive liver disease,” said John McHutchison, M.D., Principal Investigator for the PROVE 3 Study and Associate Director of Duke Clinical Research Institute.

A summary of available on-treatment and post-treatment antiviral data from the 24-week telaprevir-based regimen is presented below:

Undetectable HCV-RNA by Response to Prior Peg-IFN/RBV Treatment (PROVE 3 24-week regimen; 12 weeks telaprevir+peg-IFN+RBV, followed by 12 weeks peg-IFN+RBV); intent-to-treat analysis

Week 12 Week 24 (end of treatment) SVR 12 (week 36; 12 weeks post-treatment)
Non-responders(n=66) 71% 65% 41%
Relapsers (n=40) 88% 83% 73%
Breakthroughs (n=9) 44% 44% 44%
Total (n=115) 75% 70% 52%

In the control arm (n=114), which is evaluating 48 weeks of peg-IFN and RBV only, available data indicate that 8% of patients had undetectable HCV RNA at week 12, and 30% had undetectable HCV RNA at week 36 on-treatment (intent-to-treat analysis). In prior studies of peg-IFN and RBV in treatment-failure patients, the proportion of patients who had undetectable HCV RNA at week 36 of treatment has been significantly higher than the proportion who ultimately achieved SVR. End-of-treatment and post-treatment data (including SVR rates) are not yet available for this study arm in PROVE 3.

In addition to the 24-week telaprevir-based regimen that includes ribavirin and the 48 week control arm described above, two other treatment regimens are being evaluated in PROVE 3: a 24-week telaprevir treatment arm without ribavirin, and a 48-week treatment arm that includes 24 weeks of telaprevir dosing in combination with peg-IFN and RBV. The interim analysis supports the inclusion of ribavirin in future studies of telaprevir-based regimens in treatment-failure patients, similar to what has been observed in treatment-naïve subjects. In addition, available on-treatment results suggest that additional dosing of telaprevir beyond 12 weeks does not confer additional benefit to patients. Patient dosing has now been completed in PROVE 3 and all patients are now being followed post-treatment. Vertex anticipates that PROVE 3 data will be the subject of a presentation at a medical conference later in 2008.

“These are the first data to show the potential of a STAT-C agent to have this degree of antiviral response in patients—including both non-responders and relapsers—who did not achieve SVR with prior treatment. The interim data suggest that a telaprevir-based regimen could be an important future treatment option for genotype 1 hepatitis C patients who have failed a prior course of treatment,” said John Alam, M.D., Executive Vice President, Medicines Development, and Chief Medical Officer of Vertex. “We are now planning to begin a Phase 3 clinical trial with telaprevir in patients who failed prior peg-IFN and ribavirin treatment.”

In the interim analysis, adverse events were similar to those commonly observed with peg-IFN and RBV including fatigue, nausea, rash, headache, gastrointestinal disorders and anemia, and were also consistent with those previously reported in patients being treated with telaprevir-based therapy in the PROVE 1 and 2 studies in treatment-naïve subjects. Thirteen patients (11%) receiving the 24-week telaprevir based treatment regimen (12 weeks of telaprevir in combination with peg-IFN and RBV, followed by 12 weeks of peg-IFN and RBV alone) discontinued treatment due to adverse events. The most common reason for discontinuation among patients receiving this 24-week telaprevir–based treatment regimen was rash (7% of patients). In the control arm, 5 patients (4%) discontinued treatment prior to week 36 due to adverse events.

Phase 3 Study in Patients Who Failed Prior Treatment

Vertex and Tibotec plan to initiate a Phase 3 clinical trial in genotype 1 HCV patients who have failed prior treatment with peg-IFN and RBV in the third quarter, which will be led by Tibotec. The randomized, double-blind and placebo-controlled study will focus on regimens of 48 weeks total treatment duration, in which telaprevir is administered for 12 weeks, with a goal of maximizing SVR rates. The study is planned to be conducted at more than 50 centers in the U.S., E.U. and certain other countries.

Updates on the status of Vertex and Tibotec's clinical trials of telaprevir are available at www.clinicaltrials.gov.

About PROVE 3

PROVE 3 is an ongoing, four-arm, Phase 2b clinical trial of 453 genotype 1 HCV patients who did not achieve an SVR with a prior course of peg-IFN and RBV treatment. The study includes patients with compensated cirrhosis. The study is assessing patients who receive telaprevir-based treatment regimens of 24 and 48-week total duration, compared to a 48-week control arm of peg-IFN and RBV. PROVE 3 is being conducted at 50 clinical centers in the U.S. and the E.U.

About Telaprevir (VX-950)

Telaprevir (VX-950) is an investigational oral inhibitor of HCV protease, an enzyme essential for viral replication, and is the most advanced investigational agent in development that specifically targets HCV. Telaprevir is the first hepatitis C protease inhibitor in Phase 3 clinical trials. The Phase 3 ADVANCE trial is expected to enroll 1,050 treatment-naïve genotype 1 HCV patients and will evaluate two 24-week telaprevir-based regimens in comparison to a 48-week control arm. Vertex is also conducting a global Phase 2b clinical development program of telaprevir, including PROVE 1 and PROVE 2 in treatment-naïve genotype 1 HCV patients, and PROVE 3 in genotype 1 HCV patients who have not achieved SVR with a prior course of pegylated interferon-based therapy.

Vertex retains commercial rights to telaprevir in North America. Vertex and Tibotec are collaborating to develop and commercialize telaprevir in Europe, South America, Australia, the Middle East, and other countries. Vertex is collaborating with Mitsubishi Pharma to develop and commercialize telaprevir in Japan and certain Far East countries.
<<


Let’s talk biotech!
“The efficient-market hypothesis may be
the foremost piece of B.S. ever promulgated
in any area of human knowledge!”