Vertex to commence Phase 3 Telaprevir trials

including null responders, partial responders and relapsers

Aug 19, 2008 -- Vertex Pharmaceuticals Incorporated today announced that the Company has reached agreement with U.S. and E.U. regulatory authorities to proceed with the REALIZE trial, a pivotal Phase 3 clinical trial with the hepatitis C virus (HCV) protease inhibitor telaprevir in combination therapy for patients with chronic HCV infection who failed to achieve a sustained viral response (SVR) with prior therapy.

The trial will be conducted in the U.S. and E.U. and will enroll approximately 650 genotype 1 HCV patients who failed prior treatment with pegylated-interferon (peg-IFN) and ribavirin (RBV). The trial is designed to evaluate two 48-week telaprevir-based regimens in comparison with a 48-week control arm. Telaprevir will be dosed for 12 weeks. The primary endpoint of the trial is SVR, defined as undetectable HCV RNA (less than10 IU/mL) 24 weeks after the completion of treatment.

The REALIZE Trial (Re-treatment of Patients with Telaprevir-based Regimen to Optimize Outcomes) will enroll approximately 650 genotype 1 HCV patients and will be conducted by Tibotec at more than 100 centers in the U.S. and E.U. Tibotec expects to complete enrollment of the REALIZE trial in the first quarter of 2009. The trial will include the following patient groups:

- Null responders (defined as patients who achieved less than 2 log reduction in HCV RNA at Week 12 of prior therapy);
- Partial responders (defined as patients who achieved at least a 2 log reduction at Week 12, but failed to achieve undetectable HCV RNA by Week 24 of prior therapy); and
- Relapsers (defined as patients who had undetectable HCV RNA at the completion of at least 42 weeks of prior treatment, but relapsed during follow-up).
The REALIZE trial will dose telaprevir in combination with pegylated interferon alfa-2a (PEGASYS) and ribavirin. The REALIZE trial will enroll three 48-week trial arms:
1. Telaprevir dosed at 750 mg every eight hours (q8h) for 12 weeks in combination with standard doses of peg-IFN and RBV, followed by 36 weeks of treatment with peg-IFN and RBV alone;
2. Delayed start arm, comprised of 4 weeks of treatment with peg-IFN and RBV, followed by telaprevir dosed at 750 mg q8h for 12 weeks in combination with standard doses of peg-IFN and RBV, followed by another 32 weeks of peg-IFN and RBV alone; and
3. A control arm with standard doses of peg-IFN and RBV dosed for 48 weeks

Patients in all treatment arms will be followed for 24 weeks after completion of treatment to assess SVR.

Vertex and Tibotec are also conducting the global 3-arm pivotal Phase 3 ADVANCE trial in treatment-naive genotype 1 HCV patients that is focused on 24-week telaprevir-based regimens for patients achieving rapid viral response (HCV RNA less than 10 IU/mL at 4 weeks). Vertex is on track to complete enrollment of the ADVANCE trial during the fourth quarter of 2008 and expects to have sustained viral response (SVR) data from the trial in the first half of 2010.

Updates on the status of Vertex and Tibotec's clinical trials of telaprevir are available at http://clinicaltrials.gov/ct2/results?term=hepatitis+c+telaprevir

"Approximately 6 million patients are chronically infected with hepatitis C in the U.S. and E.U. today, and approximately 650,000 of these patients have failed previous treatments of pegylated interferon and ribavirin therapy and are in need of a new therapeutic option to treat their disease," said Kurt C. Graves, Vertex's Executive Vice President, Chief Commercial Officer and Head, Strategic Development. "Data generated from this Phase 3 trial in treatment-failure patients, as well as data from the ongoing Phase 3 ADVANCE trial in treatment-naive patients, may further contribute to the emerging profile of telaprevir to address the significant medical need in both treatment-naive and treatment-failure patients."

www.thestreet.com Vertex Pharmaceuticalsannounced Tuesday an agreement with regulators in the U.S. and Europe that greenlights the company and partner Johnson & Johnson to begin a new phase III study of their experimental hepatitis C drug telaprevir.

The new study will test telaprevir with standard combination therapy in 650 hepatitis C patients who could not be cured with the currently approved drugs for the disease, pegylated interferon and ribavirin. These are difficult to treat patients, including patients known as "null responders," which means they did not respond at all to previous treatments.

Vertex and Johnson & Johnson, which are co-developing telaprevir, posted an outline of this new study, dubbed REALIZE, on the ClinicalTrials.gov web site in June. Vertex shares fell at that time because the new phase III trial suggested that an early regulatory approval filing for telaprevir in 2009 for treatment-resistant patients was not in the cards.

As it stands now, Vertex and Johnson & Johnson won't likely seek approval for telaprevir until the second half of 2010, based on data from a separate phase III study of the drug in treatment-naïve hepatitis C patients.

Vertex and its partner have previously released results from a smaller study in treatment-resistant patients that showed telaprevir to be effective in attacking the virus that causes hepatitis C.

The new phase III study announced today will test two different regimens of telaprevir in patients who previously did not respond to conventional hepatitis C treatment with pegylated interferon and ribavirin.

The study differs from previous studies in that patients will be treated with two regimens of telaprevir for a full 48 weeks instead of the accelerated 24-week treatment cycle used for treatment-naïve patients.

In addition, one of the arms of the new study will see whether a "lead-in" treatment with interferon and ribavirin alone before dosing of telaprevir may improve overall cure rates.

Vertex and its partner are locked in a tight race with Schering-Plough to be the first with a new direct antiviral drug aimed at hepatitis C approved in the U.S. and Europe.