Tobira Therapeutics ($TBRA) fell by about half in premarket trading on news that its Phase IIb trial to treat nonalcoholic steatohepatitis (NASH) failed to meet the primary endpoint. The South San Francisco, CA-based company aims to trudge ahead, though, by shifting a secondary endpoint that it did meet in Phase IIb into the new primary endpoint for Phase III, with a trial start slated for next year.
The Phase IIb trial for Tobira’s cenicriviroc (CVC) did not meet the primary endpoint of a two-point reduction in the nonalcoholic fatty liver disease Activity Score; the 289-patient trial did meet one of two key secondary endpoints, improvement in fibrosis of at least one stage without worsening NASH, in adult liver fibrosis patients after a year of treatment.
This will become the primary endpoint for the Phase III testing, the company said. It specified that regulators had identified this as sufficient to support a marketing application--despite the fact that the Phase IIb trial was the first one to use it as a prespecified endpoint.
The study did not meet another secondary endpoint: the complete resolution of steatohepatitis.
In addition, the company plans to start a Phase I trial by year end of CVC in combination with its second candidate, evogliptin, which is expected to target metabolic abnormalities.
Regulators are likely under pressure--with the growing incidence of obesity and the more frequent occurrence of its comorbidities--to offer a treatment for NASH, which has no approved drug to treat it.
“Liver fibrosis is the most important feature of NASH and is independently associated with key outcomes including long-term overall mortality, liver transplantation, and liver-related events,” said Dr. Scott Friedman, chief of the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai, in a statement. He was the chairman of the Phase IIb study, known as CENTAUR.
Continued Friedman, “The very favorable safety profile of CVC combined with the efficacy data underscore the potential of CVC to emerge as a treatment of fibrosis associated with NASH, at a time when there are no approved therapies yet for this growing epidemic.”
The study found that after a year of treatment with CVC, more patients improved by at least one stage of fibrosis without worsening of steatohepatitis as compared to placebo. It was active across all three stages of fibrosis.
“We designed the CENTAUR trial to explore a number of registrational and non-registrational endpoints and achieved statistical significance on the most clinically relevant– regression in fibrosis after only one year of treatment,” said Tobira CMO Dr. Laurent Fischer. “These data exceeded our expectations and we plan to meet with regulators later this year to discuss the Phase III study design. The CENTAUR patient population is similar to the anticipated Phase III population, and we expect to initiate a global pivotal study in 2017 to confirm CVC’s anti-fibrotic activity to address this high unmet medical need.”
Tobira saw its market cap cut to less than $100 million.
- here is the release
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