Vertex to Start Phase 3 Trials of HCV Protease Inhibitor Telaprevir (VX-950)

[Guest guest]

Vertex to Start Phase 3 Trials of HCV Protease Inhibitor Telaprevir

(VX-950)

Vertex Pharmaceuticals announced last week that it will soon begin

Phase 3 development of telaprevir (VX-950), the company's

investigational HCV protease inhibitor.

As previously reported, in the Phase 2b PROVE studies, telaprevir

demonstrated promising antiviral activity when used with pegylated

interferon alfa-2a (Pegasys) plus ribavirin in previously untreated

genotype 1 patients, and may allow for a shorter duration of

combination therapy.

Below is an edited excerpt from Vertex's recent press release

announcing the new phase of drug development:

Vertex Pharmaceuticals to Begin Phase 3 Development of Telaprevir,

Investigational Hepatitis C Protease Inhibito

• Primary Phase 3 trial will focus on studying 24-week telaprevir-

based regimens

• Vertex plans concurrent second study to support registration

• Final data from both trials anticipated in mid- 2010

CAMBRIDGE, Mass. Wednesday January 23, 7:00 am ET -- BUSINESS WIRE --

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced

that it will begin Phase 3 evaluation of telaprevir, Vertex's lead

investigational hepatitis C protease inhibitor. The primary focus

will be a global, 3-arm pivotal controlled trial that will evaluate

two 24-week telaprevir-based regimens in approximately 1050 treatment-

naive genotype 1 HCV patients. In this study, rapid viral response

(RVR) criteria will be used to determine which telaprevir patients

can stop all treatment at 24 weeks.

A second study of approximately 400-500 HCV patients is planned to

evaluate a 48-week telaprevir-based regimen, to confirm the results

from Phase 2 studies and provide additional evidence that supports

the 24-week regimen that is being evaluated in the primary Phase 3

trial. The company expects that both studies will run concurrently

and that the first trial will begin

" Data presented in late 2007 from two large Phase 2b studies suggest

that telaprevir, dosed in combination with pegylated interferon and

ribavirin, may be able to meaningfully increase the proportion of

treatment-naive genotype 1 HCV patients who achieve a sustained viral

response, and also cut the current treatment duration in half, to 24

weeks, " said McHutchison, MD, Principal Investigator for the

primary telaprevir Phase 3 pivotal study and Associate Director of

Duke Clinical Research Institute. " Telaprevir is the most advanced

protease inhibitor in development for hepatitis C, and the initiation

of Phase 3 clinical development for this investigational drug will

begin the process of helping to further assess its potential efficacy

and the safety in a larger number of patients. "

Pivotal Trial to Evaluate 24-Week Telaprevir-Based Treatment Regimens

In accordance with the design and protocol Vertex submitted to the

FDA, the primary pivotal trial will focus on evaluation of 24 weeks

of telaprevir-based therapy and will enroll approximately 1050

treatment-naive, genotype 1 HCV patients, who will be randomized

equally across three treatment arms (approximately 350 patients per

arm).

The study will be conducted at approximately 100 centers in the U.S.,

European Union, and certain other countries. The study arms will

include:

• 24 weeks of therapy, with telaprevir dosed at 750 mg every 8 hours

for 12 weeks in combination with standard doses of pegylated

interferon alfa-2a and ribavirin for 12 weeks, then continuing for

another 12 weeks with pegylated interferon and ribavirin alone;

• 24 weeks of therapy, with telaprevir dosed at 750 mg every 8 hours

for 8 weeks in combination with standard doses of pegylated

interferon and ribavirin for 8 weeks, then continuing for another 16

weeks with pegylated interferon and ribavirin alone; and

• A control arm with standard doses of pegylated interferon and

ribavirin dosed for 48 weeks.

Patients in both telaprevir arms who achieve rapid viral response

(RVR), defined as undetectable (less than 10 IU/mL) viral levels by

the end of week 4, and who stay undetectable at week 12 will receive

24 weeks of treatment. Patients in these treatment arms who do not

meet the RVR criteria but are undetectable at week 24 will continue

on pegylated interferon and ribavirin for a total duration of 48

weeks.

Concurrent 48-Week Second Study to Support Registration

Vertex has agreed to conduct a second well-controlled clinical study

as part of the registration program for a treatment-naive indication.

The objective of this second study would be to develop additional

sustained viral response (SVR) and relapse rate data with 48-weeks

treatment duration that confirm results from the Phase 2 studies,

thereby providing additional evidence supporting the 24-week regimen

in the Phase 3 trial. The design of this second study is being

finalized, but at this time Vertex expects this study to enroll

approximately 400-500 patients, including patients in the control arm.

The primary objective of the two studies will be to assess the

proportion of patients in each study arm who achieve SVR, defined as

undetectable (less than 10 IU/mL, as measured by the Roche TaqMan

assay) HCV RNA 24 weeks after the completion of dosing. Vertex

expects to have SVR data from both studies by mid-2010.

Update on Meeting with FDA

Vertex and the FDA met in mid-January 2008 to discuss telaprevir's

Phase 3 development program. This meeting included a review of

available data from Phase 2b clinical trials of telaprevir, including

newly available post-treatment data from the 48-week treatment arms

in PROVE 1. In the control arm of PROVE 1, on an intent-to-treat

(ITT) basis, 37% of patients had undetectable HCV RNA at 12 weeks

post-treatment follow-up. In the 48-week ( " 12+36 " ) telaprevir-based

treatment arm in PROVE 1, also on an ITT basis, 66% of patients had

undetectable HCV RNA at 12 weeks post-treatment follow-up. The

relapse rate in the 48-week telaprevir-based arm in PROVE 1 was 6%.

Additional HCV Studies

Vertex and Tibotec continue to conduct additional clinical studies to

evaluate the potential role of telaprevir treatment for important HCV

sub-populations as well as different dosing regimens for telaprevir.

• The companies are conducting PROVE 3, a Phase 2b clinical trial of

telaprevir-based combination therapy in patients with genotype 1 HCV

who have not achieved SVR with a previous pegylated interferon-based

treatment. Vertex plans to discuss with regulatory authorities in mid-

2008 the next steps in the telaprevir development program for

treatment-failure HCV patients after the first interim clinical data

are available from the PROVE 3 clinical trial.

• Tibotec is conducting a Phase 2 clinical study in Europe to

evaluate 8-hourly and 12-hourly dosing of telaprevir in com

bination with pegylated interferon (Pegasys or PegIntron) and

ribavirin. Interim 12-week on-treatment data are expected to be

available in the second half of 2008.

• Tibotec is also conducting a Phase 2 viral kinetics study in Europe

to evaluate telaprevir in patients infected with genotype 2/3 HCV.

Interim on-treatment data are expected to be available in late 2008.

• In addition, in December 2007, Tibotec initiated a Phase 2 study in

Europe to evaluate telaprevir in patients infected with genotype 4

HCV.

Updates on the status of Vertex and Tibotec's clinical trials of

telaprevir are available at www.clinicaltrials.gov.

About Vertex

Vertex Pharmaceuticals Incorporated is a global biotechnology company

committed to the discovery and development of breakthrough small

molecule drugs for serious diseases. The company's strategy is to

commercialize its products both independently and in collaboration

with major pharmaceutical companies. Vertex's product pipeline is

focused on viral diseases, inflammation, autoimmune diseases, cancer,

pain and bacterial infection. Vertex co-discovered the HIV protease

inhibitor, Lexiva [fosamprenavir], with GlaxoKline.

For further information about Vertex, visit www.vpharm.com.

02/01/08

Source