Bristol-Myers Squibb and Tibotec Pharmaceuticals are teaming up to carry out a Phase II clinical study evaluating the combination of their respective HCV candidates, daclatasvir (BMS-790052) and TMC435. BMS’s daclatasvir is an NS5A replication complex inhibitor, and Tibotec’s TMC435 is an NS3 protease inhibitor, which the Janssen-owned firm is developing in partnership with Medivir. Both drugs are currently in Phase III development by their respective firms.
The Phase II combination trial in patients with HCV type 1 is scheduled to start during the first half of 2012, and will assess whether combining therapy using daclatasvir and TMC435 leads to a sustained viral response at 12 and 24 weeks. Enrolled patients will receive one of three treatment regimens. One will involve oral, once-daily treatment using daclatasvir and TMC435, along with therapy using peginterferon alpha plus ribavrin. A second regimen will involve once-daily treatment using once-daily daclatasvir and TMC435, plus ribavirin. The third will comprise once-daily daclatasvir and TMC435 alone.
Tibotec’s TMC435 is currently being developed in three global Phase III studies, QUEST-1 and QUEST-2 in treatment-naïve patients, and the PROMISE study in patients who have relapsed after prior interferon-based treatment. In parallel with these trials, Phase III studies for TMC435 are ongoing in Japan, in both treatment naive and treatment experienced hepatitis C genotype-1 infected patients.
In November, Tibotec reported positive data from the Phase IIb PILLAR study evaluating TMC435 in treatment-naïve patients with chronic HCV genotype 1 infection. The trial data showed that TMC435 administered in combination with peginterferon α-2a and ribavirin (PR) resulted in significantly higher sustained virologic response (SVR) rates compared to placebo plus PR.
Also in November, BMS reported interim results from a Phase IIb clinical trial (COMMAND-1) evaluating two doses of the daclatasvir, in combination with peginterferon alfa and ribavirin, in 395 treatment-naïve, genotype 1 and 4 hepatitis C-infected patients. The data confirmed that patients in the daclatasvir groups achieved higher virologic response rates through Week 12 than those in the group receiving peginterferon alfa and ribavirin.