Biotech Values

[DewDiligence]

This is VRTX’s PROVE-3 PR from EASL. The only difference between what’s
reported here and what was reported in March (#msg-36464842) is a small
amount of additional color on the “24+24” and control-arm relapse rates and
a subset analysis of cirrhosis vs. no-cirrhosis, which found no difference.
A notable outcome is that the ITT SVR rates in the “12+12” arm and the
“24+24” arm were almost exactly the same, despite the higher relapse rate
in the “12+12” arm; the lower dropout rate in the “12+12” arm relative to the
“24+24” arm almost exactly offset the higher relapse rate.

In the phase-3 Telaprevir trial in the second-line setting (#msg-32901932),
the two Telaprevir trial arms are “12+36” and “4+12+32” — the latter has
a 4-week lead-in period with SoC only before starting Telaprevir, which is
an idea VRTX borrowed from SGP’s phase-2 Boceprevir trial. Also, the
subgroup categories based on outcome in the first-line setting are different
in phase-3: instead of the non-responder, relapser, and breakthrough
categories, phase-3 uses the null-responder, partial-responder, and
relapser categories.

http://investors.vrtx.com/releasedetail.cfm?ReleaseID=379752

›Telaprevir Data Presented at EASL Show Unprecedented SVR Rates in HCV Treatment-Failure Patients in PROVE 3 Study

- Superior SVR rates with telaprevir across all HCV genotype 1 non-responders and relapser patients and patients with cirrhosis – up to 76% in prior relapsers -

- PROVE 3 showed 51% and 52% SVR rates in telaprevir-based regimens compared to 14% in the 48-week control arm -

- Treatment-failure patient population represents the greatest unmet medical need in HCV -

Saturday April 25, 2009, 12:00 pm EDT

COPENHAGEN--(BUSINESS WIRE)--Unprecedented sustained viral response (SVR) rates were achieved in hepatitis C-infected treatment-failure patients, including those with cirrhosis, with telaprevir-based treatment according to PROVE 3 trial results presented today in the late breaker session at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL) in Copenhagen, Denmark. Telaprevir is being developed by Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX ) in collaboration with Tibotec and Mitsubishi Tanabe Pharma.

In this intent-to-treat analysis, 51% and 52% of treatment-failure patients achieved SVR in the 24-week and 48-week telaprevir-based regimens, respectively. In comparison, SVR rates were achieved by 14% of patients randomized to receive 48 weeks of peg-IFN and RBV alone. Adverse events were generally consistent with those reported in prior telaprevir Phase 2 trials.

"Previously treated patients who didn’t achieve SVR represent the hardest to treat patient population in physicians’ practices,” said Michael P. Manns, M.D., Principal Investigator for the PROVE 3 Study and Director of the Department of Gastroenterology, Hepatology and Endocrinology at Medical School of Hannover, Germany. “Today’s compelling PROVE 3 results represent important progress as we seek to address a serious unmet need in patients who currently have very few options. We observed superior SVR rates across all telaprevir-based treatment arms compared to the control arm in patients who had previously failed treatment for hepatitis C, including patients with cirrhosis. This represents an exciting potential medical advance.”

“The SVR rates achieved in this difficult-to-treat population, with safety results consistent with prior telaprevir studies, add to the growing body of data supporting further development of telaprevir across the broad HCV patient population,” said Freda Lewis-Hall, M.D., Executive Vice President, Medicines Development and Chief Medical Officer at Vertex. “Telaprevir is the only STAT-C agent to show SVR rates at this level in the treatment-failure patient group.”

PROVE 3 SVR Results

PROVE 3 was 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, prior relapsers and prior breakthroughs to peg-IFN and RBV treatment. The results included 453 patients who were enrolled and received at least one dose of study drug.

A summary of available on-treatment and post-treatment antiviral data from the 24-week telaprevir-based regimen compared to the 48-week standard of care regimen is presented below:

PROVE 3 Sustained Viral Response rates; intent-to-treat analysis

 
                      TVR12/PR24   TVR24/PR48  Control arm  
  Non-responders [1]  39% (n=66)   38% (n=64)    9% (n=68)  
  Relapsers [2]       69% (n=42)   76% (n=41)   20% (n=41)  
  Breakthroughs [3]   57% (n=7)    50% (n=8)    40% (n=5)  
  ===                 ==========   ==========   ==========  
  Total               51% (n=115)  52% (n=113)  14% (n=114)

[1] Non-responders are defined as patients who never achieved undetectable HCV RNA during or at the end of prior therapy.

[2] Relapsers are defined as patients who achieved undetectable HCV RNA at the completion of prior treatment, but relapsed during follow-up.

[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.

Sixty-nine and 76% of prior relapsers in the 24- and 48-week telaprevir-based treatment arms, respectively, achieved SVR as compared to 20% in the control arm, and 39% and 38% of prior non-responders in the 24- and 48-week telaprevir-based treatment arms, respectively, achieved SVR as compared to 9% in the control arm. A sub-analysis showed that 53% and 45%, respectively, of patients with cirrhosis in the 24- and 48-week telaprevir-based treatment arms achieved SVR compared to 8% in the control arm – these results were similar to those obtained for patients without cirrhosis [an important and surprising finding].

In PROVE 3, an overall relapse rate of 13% (10 of 76 patients) was observed in patients in the 48-week telaprevir-based treatment regimen arm, while patients in the control arm relapsed at a rate of 53% (18 of 34 patients). A third arm of the study, evaluating a 24-week telaprevir-based regimen, showed a similar SVR rate compared to the 48-week telaprevir arm and an overall relapse rate of 30% (26 of 87 patients). In a completers' analysis, a relapse rate of 4% (2 of 53 patients) was observed in patients who completed treatment with a 48-week telaprevir-based treatment regimen, while patients who completed treatment in the control arm relapsed at a rate of 52% (17 of 33 patients). A third arm of the study, evaluating a 24-week telaprevir-based regimen, had a relapse rate of 28% (22 of 80 patients) in patients who completed treatment with a 24-week telaprevir-based regimen. These results suggest that a telaprevir-based regimen that includes a total of 48 weeks of treatment with peg-IFN and RBV including 12 weeks of telaprevir may be warranted in treatment-failure patients. REALIZE, a Phase 3 study designed to evaluate this treatment regimen in non-responders (null and partial responders) and relapsers, is currently underway.

Safety and Tolerability in PROVE 3

In PROVE 3, adverse events were generally consistent with those reported in prior Phase 2 telaprevir trials including fatigue, nausea, headache, rash, pruritus, diarrhea, insomnia, pyrexia, alopecia, and chills. In the PROVE 3 telaprevir treatment arms, rash led to discontinuations in 5% of patients (17 of 339) and was manageable and reversible upon cessation of treatment. A 1% discontinuation rate due to anemia (3 of 339) was observed which was similar to that in the control arm. Erythropoiesis stimulating agents (ESA) were not recommended for the PROVE 3 study and were rarely used (in less than 1% (2 of 339) of patients) in the telaprevir-based treatment arms.‹