Janssen announces safety results from two Phase 3 studies of simeprevir in hepatitis C patients

Janssen R&D Ireland (Janssen) today announced primary efficacy and safety results from two global Phase 3 studies demonstrating that use of the investigational protease inhibitor simeprevir (TMC435) led to sustained virologic response 12 weeks after the end of treatment (SVR12) in 80 and 81 percent, respectively, of treatment-naive genotype 1 chronic hepatitis C adult patients with compensated liver disease, including all stages of liver fibrosis, when administered once daily with pegylated interferon and ribavirin. In both studies, 50 percent of patients receiving pegylated interferon and ribavirin alone achieved SVR12.

The data will be presented this week at The International Liver Congress 2013 of the European Association for the Study of the Liver (EASL) in Amsterdam, The Netherlands. The QUEST-1 and QUEST-2 data will be discussed in an official EASL press conference on April 24 at 11:00 a.m. CEST.

"More than 390 treatment-naive genotype 1 hepatitis C patients in 39 countries received simeprevir as part of the Phase 3 QUEST trials," said Michael Manns , M.D., professor and chairman, Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover. "I am pleased to be a part of these robust studies and look forward to seeing the results from upcoming trials of simeprevir in treatment-experienced patients later this year."

In QUEST-1 and QUEST-2, patients were randomized to receive simeprevir or placebo for 12 weeks plus pegylated interferon and ribavirin for 24 or 36 weeks. In findings related to a secondary endpoint, 85 percent (QUEST-1) and 91 percent (QUEST-2) of patients receiving simeprevir were able to shorten therapy with pegylated interferon and ribavirin to 24 weeks due to meeting response-guided therapy (RGT) criteria. Of those patients meeting RGT criteria to stop treatment at 24 weeks, 91 percent (QUEST-1) and 86 percent (QUEST-2) of patients achieved SVR12.

"Given the long-term health risks associated with hepatitis C, it's important that physicians and patients have multiple options to treat the disease," said Ira Jacobson , M.D., chief of the Division of Gastroenterology and Hepatology, Vincent Astor Distinguished Professor of Medicine, Weill Cornell Medical College, and attending physician, New York-Presbyterian Hospital/Weill Cornell Medical Center. "The results of these Phase 3 trials suggest that simeprevir could represent an important new treatment option for people living with genotype 1 chronic hepatitis C."

Patients enrolled in QUEST-1 and QUEST-2 were stratified by HCV genotype 1 subtype and IL28B genotype. In QUEST-1, SVR12 rates among patients treated with simeprevir with IL28B genotype variations were 94 percent for the CC allele, 76 percent for the CT allele, and 65 percent for the TT allele. In QUEST-2, SVR12 rates among patients treated with simeprevir with IL28B genotype variations were 96 percent for the CC allele, 80 percent for the CT allele, and 58 percent for the TT allele. Among patients with METAVIR scores F3 and F4, 70 percent of patients treated with simeprevir in QUEST-1 and 66 percent of patients treated with simeprevir in QUEST-2 achieved SVR12. Among patients with METAVIR scores F0 to F2, 83 percent of patients treated with simeprevir in QUEST-1 and 85 percent of patients treated with simeprevir in QUEST-2 achieved SVR12. The METAVIR score is used to quantify the degree of inflammation and fibrosis of the liver and patients are scored on a four-point scale. 

"Patient response rates to hepatitis C therapy can be variable, depending on factors such as viral genotype and subtype, and liver fibrosis. Patients with genotype 1a, IL28B genotype TT and METAVIR scores of F3 and F4 can be particularly challenging to cure," said Maria Beumont , M.D., medical leader for simeprevir, Janssen. "Janssen is committed to advancing hepatitis C therapy for even the most difficult-to-cure patients."

The most common adverse events seen in patients receiving simeprevir in QUEST-1 were fatigue (42 percent versus 41 percent for placebo), itch (26 percent versus 16 percent for placebo), and headache (33 percent versus 39 percent for placebo). The most common adverse events seen in patients receiving simeprevir in QUEST-2 were fatigue (37 percent versus 42 percent for placebo), itch (25 percent versus 25 percent for placebo), headache (39 percent versus 37 percent for placebo), fever (31 percent versus 40 percent for placebo), and influenza-like illness (26 percent versus 26 percent for placebo). In QUEST-1, in both the simeprevir and placebo arms, 3 percent of patients discontinued treatment due to an adverse event. In QUEST-2, 2 percent of patients in the simeprevir arm and 1 percent of patients in the placebo arm discontinued treatment due to an adverse event.