Drug Development

UPDATED: Tobira crushed after NASH drug flunks a PhIIb, but slice of data drives PhIII plans

Tobira Therapeutics’ $TBRA lead drug cenicriviroc flunked a Phase IIb study for NASH, but the South San Francisco-based biotech says it got enough positive data on a secondary endpoint to warrant a move into a pivotal Phase III program,.

Tobira’s shares were crushed by the news, plunging 64% in premarket trading.

The primary endpoint in the study, which registered 289 patients, was a drop in a score for disease activity in NASH, a fatty liver ailment that has been growing at an epidemic pace around the world. On that point, the drug flopped. It also failed a secondary endpoint for complete resolution of steatohepatitis.

But Tobira vowed that it had a good reason to launch a late-stage program, looking for an improvement in fibrosis without any worsening of steatohepatitis. The data for the intent-to-treat population in Phase IIb was 20% for the drug vs 10% for placebo after a year of treatment, p=0.02; in other words, twice as many patients on drug had a marked improvement for fibrosis, but it was a small group.

“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,” said CEO Laurent Fischer in a statement. Talking to analysts, Fischer hammered on his point that this is the first such study that had seen a positive impact on NASH.

Investors weren’t sticking around, though, reacting quickly to the key failure on NASH activity.

Company execs said this morning that they could detect no difference between the drug and a placebo in the study data for NASH.

“They (the drug arm and placebo group) were equal with no statistically sign difference between the two,” Chief Medical Officer Eric Lefebre told analysts in a call this morning.

NASH has been a prime target in the biopharma world. Just a few months ago Gilead paid a whopping $400 million upfront to land rights to a NASH drug from Nimbus. Intercept gained an approval for its drug OCA for primary biliary cirrhosis, and is now seeking to prove that it can work against NASH. And a large number of other drugs for NASH are in the clinic.

“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 Scott L. Friedman, M.D., chief, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai and CENTAUR study chairman. “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.”

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