Tobira Fails Main Goal in NASH Study, But Forges Ahead To Next Trial

Xconomy San Francisco — 

[Updated, 9:40 a.m. ET, see below] Developing treatments for nonalcoholic steatohepatitis, a dangerous liver disease that’s fast becoming an epidemic, is one of the most competitive fields in biotech. Tobira Therapeutics is one of several companies in the mix, and although data released this morning cast doubt on the potential of its drug, the company plans to forge ahead nonetheless.

Tobira (NASDAQ: TBRA) posted results this morning from a mid-stage trial of cenicriviroc, or CVC, a drug the company is developing for nonalcoholic steatohepatitis, or NASH. The drug failed to meet its main goal, which was to improve inflammation and liver damage after a year of treatment, as measured by what’s known as the NAFLD Activity Score. CVC also failed to hit one of two secondary goals, which was to show a complete resolution of patients’ steatohepatitis—the inflammation and fat accumulation in the liver in NASH patients.

But Tobira instead pointed to other positive signs, such as a “clinically and statistically significant” improvement in fibrosis, or the liver scarring typical in NASH. Those data, Tobira says, are justification to move the drug into a Phase 3 trial next year. Regulators, Tobira argued, consider improvement in fibrosis a valid endpoint to support an approval application. Stability in fibrosis, rather than improvement, is a component of patients’ NAFLD Activity Scores.

[Updated with comments from conference call] On a conference call with analysts this morning, Tobira executives downplayed the fact that CVC missed its main goal and instead focused on, and expressed surprise about, its apparent effect on fibrosis. Tobira CEO Laurent Fischer said CVC’s lack of impact on NAFLD Activity Score is evidence that NASH is a “complex, multi factorial, heterogeneous disease” and that different drugs may impact the various symptoms of the disease differently.

“To be frank, [improving fibrosis] is a higher hurdle and we believe that is more likely to be more meaningful for patients with this disease,” Fischer said on the call. “We did not anticipate that we’d have such a significant effect on fibrosis after one year of treatment.”

Chief medical officer Eric Lefebvre added that the company designed its mid-stage trial, known as Centaur, a few years ago when less was known about NASH, and that’s why a change in NAFLD Activity Score was its main goal. “Since then we’ve learned quite a bit about clinical research and the regulatory landscape,” Lefebvre said, adding that in recent talks with the FDA Tobira was told that a reduction in NAFLD Activity Score “was not acceptable” as a goal in a late-stage clinical trial.

Investors weren’t buying Tobira’s assessment. Shares of Tobira plummeted more than 50 percent in pre-market trading, to $5.50 from an $11.25 close on Friday.

Tobira didn’t provide much data at all in the release. The only number it provided was that 20 percent of patients on CVC, compared to 10 percent of patients on placebo, saw an improvement in their fibrosis by at least one stage, as measured by a standardized test of liver scarring. Tobira said the drug performed comparably to a placebo on the safety side. The most common side effects were fatigue and diarrhea.

NASH is an increasingly common liver disorder and a leading cause of cirrhosis and liver failure. It occurs when fat builds up in the liver, typically due to sugary and fatty diets, leading to inflammation and scarring, and potentially necessitating a liver transplant if unchecked. About 16 million people in the U.S. have the disease, the worldwide market for drugs to treat the disorder is expected to grow to $1.6 billion by 2020, according to a report from Allied Market Research. Currently there are no approved treatments for NASH.

Intercept Pharmaceuticals (NASDAQ: ICPT) of New York leads a competitive race to develop the first NASH drug. Its candidate, obeticholic acid, is currently in Phase 3 testing for the disease. Potential rivals include Gilead Sciences (NASDAQ: GILD), which has been accumulating a pipeline of NASH drugs, and France’s GenFit.

Tobira’s CVC, a tablet, is a small molecule that targets two proteins on the surface of certain white blood cells—CCR2 and CCR5—thought to play a role in the inflammation and internal scarring that characterizes NASH. Tobira has been developing CVC for another liver disease, primary sclerosing cholangitis, and HIV as well, but has said that it’ll only move the drug into Phase 3 testing for HIV with the help of a partner. Tobira has a second drug, evogliptin, that it aims to test in combination with CVC for NASH.

Tobira randomly assigned 289 patients to receive either a placebo or CVC for two years. The study’s primary goal is a two-point improvement  in the NAFLD activity score, which ranges from 0 to 8, after one year.

Today’s results come at that one year mark. Tobira continues to treat patients in the trial, and will provide updated results after patients are on CVC for two years.

Tobira was formed in 2006 and tried to go public via an IPO in 2014, but instead inked a reverse merger with now-defunct Regado Biosciences of Basking Ridge, NJ in January 2015 to get to the Nasdaq. CVC is Tobira’s only drug in clinical testing; its other experimental drug, evogliptin, is expected to begin its first trial later this year.

Tobira’s top shareholders as of an April proxy filing were Domain Associates (20.9 percent as of the filing), Frazier Healthcare (14.2 percent), and Novo A/S (12.1 percent).