Biotech Values

[DewDiligence]

JNJ Starts Phase-3 Trials of TMC435 in 1st/2nd-Line HCV

[TMC435 is a second-generation protease inhibitor that JNJ licensed from Medivir. All three of the phase-3 trials test SoC±TMC435 in genotyope-1 patients and use a 24w/48w “response–guided” protocol for determining when to stop treatment. The QUEST-1 and QUEST-2 trials in first-line HCV are clones; the only difference is that QUEST-1 uses Pegasys while QUEST-2 uses a choice of Pegasys or PegIntron. The PROMISE trial is in second-line HCV and is specifically for first–line relapsers (i.e. it excludes the harder-to-treat patients who never achieved undetectable virus in the in the first line). PROMISE is not being characterized as registrational, so the FDA has presumably not agreed that it alone is sufficient for approval in the second-line setting.

In phase-2b, JNJ/Medivir have reported 24-week data but not 48-week or SVR data (#msg-52204240); however, the companies presumably like the phase-2b data that have not yet been publicly disclosed.]

http://finance.yahoo.com/news/Tibotec-Starts-Global-Phase-3-prnews-3859118368.html?x=0&.v=1

›Friday February 18, 2011, 5:00 am

CORK, Ireland, Feb. 18, 2011 /PRNewswire/ -- Tibotec Pharmaceuticals announced today that two global, registrational phase 3 trials are recruiting patients to examine TMC435, its investigational hepatitis C protease inhibitor, in treatment-naive adults with chronic genotype 1 hepatitis C virus (HCV). A third global phase 3 trial is being conducted in genotype 1 HCV patients who have experienced a viral relapse after prior interferon-based treatment. Approximately 3.2 million people in the U.S. live with chronic hepatitis C disease and more than 170 million people have the disease globally. The response-guided trials will compare the efficacy, safety and tolerability of TMC435 given as a single 150 mg oral tablet once daily for 12 weeks versus placebo; each patient also will be treated with a background regimen of peginterferon and ribavirin for 24 or 48 weeks.

"TMC435 is an important component of our growing HCV pipeline," said Brian Woodfall M.D., Vice President of Global Clinical Development at Tibotec. "The initiation of the TMC435 phase 3 clinical trial program reinforces our commitment to develop innovative new treatment options that may decrease the duration of treatment for patients with chronic hepatitis C infection."

The first global, phase 3, double-blind, randomized study, known as TMC435-C208 or QUEST-1 (QD dosing of TMC435 of previoUsly untreated GEnotype 1 patienTs-1), will evaluate a single TMC435 once-daily oral tablet (150 mg) versus placebo in treatment-naïve HCV patients. Both groups will also receive peginterferon alfa-2a (Pegasys®) and ribavirin (Copegus®) as part of their treatment. The second global, phase 3, double-blind, randomized study, known as TMC435-C216 or QUEST-2 (QD dosing of TMC435 of previoUsly untreated GEnotype 1 patienTs-2), also will evaluate a single TMC435 once-daily oral tablet (150 mg) versus placebo in treatment-naive HCV patients. However, patients in this trial will either receive peginterferon alfa-2a (Pegasys®) and ribavirin (Copegus®) or peginterferon alfa-2b (PegIntron®) and ribavirin (Rebetol®) as part of their treatment. A third global, phase 3, double-blind randomized study, known as TMC435-C3007 or PROMISE (PROtease inhibitor TMC435 In PatientS who have previously rElapsed on IFN/RBV), will evaluate a single TMC435 once-daily oral tablet (150 mg) verses placebo in HCV patients who experienced viral relapse after previous interferon-based therapy. Both groups will receive peginterferon alfa-2a (Pegasys®) and ribavirin (Copegus®). The complete treatment duration for all three trials will be 24 or 48 weeks, depending on patient response.

The studies will be conducted at more than 160 sites in 24 countries, including the U.S. and countries throughout Europe, and together seek to enroll approximately 1,125 HCV genotype 1 infected patients who are treatment-naive or have experienced a relapse after previous interferon-based HCV therapy. To be eligible, patients must have chronic hepatitis C infection, and must have had a liver biopsy within three years of the screening visit. For those patients who have not had a liver biopsy in the three years prior to the study, one will be performed before the baseline visit. In addition, eligible patients need to have completed a recent ultrasound with no findings suspicious of hepatocellular carcinoma (HCC). Patients with signs of hepatic decompensation, liver disease of any non-HCV etiology, co-infection with hepatitis B or HIV-1 and 2 or a history of malignancy within 5 years of the screening vitis are ineligible for the study. Patients in QUEST-1 and QUEST-2 trials must not have received any prior treatment for hepatitis C, and patients in the PROMISE trial must have previously received at least 24 weeks of (peg)interferon-based therapy, along with documented negative HCV RNA at last on-treatment measurement, and have relapsed (detectable HCV RNA) within one year of last taking medication. The primary endpoint of the studies is to assess whether TMC435 is superior to placebo in achieving sustained virologic response (SVR), defined as HCV RNA <25 IU/ml undetectable, 24 weeks after the planned end of treatment (SVR 24), with the final analysis being performed after the last patient reaches week 72 of the study. Secondary endpoints include superiority of TMC435 versus placebo at 12 weeks (SVR 12), after planned end of treatment and at week 72 of the study. Evaluations of viral breakthroughs, relapse rates in treatment groups, safety and tolerability also will be assessed.

Phase 3 studies for TMC435 also recently launched in Japan.

For additional information on inclusion and exclusion criteria for these studies, please see www.clinicaltrials.gov or email [e-mail].‹