Galectin Therapeutics was down nearly 50% in premarket trading Tuesday on the news that its lead fibrosis candidate missed the primary endpoint of a phase 2b trial in nonalcoholic steatohepatitis (NASH) cirrhosis.
The trial enrolled 162 patients with NASH cirrhosis, the final stage of NASH, a progressive liver disease. The patients received 8 mg/kg or 2 mg/kg of the drug, or placebo, every other week for a year. Half of the patients had esophageal varices—abnormal, enlarged veins in their esophagus—while the other half did not.
The drug, GR-MD-02, showed a positive trend in reducing hepatic venous pressure gradient (HVPG), the primary endpoint, compared to placebo. But it failed to "reach statistical significance," due to more variability in HVPG readings for patients with varices, the company said in a statement.
The drug also failed to meet secondary endpoints that measured liver stiffness as a surrogate for fibrosis, or scarring.
If the study had been designed to exclude patients with esophageal varices, said Galectin CEO Peter Traber, M.D., on a conference call Tuesday, the drug would have met the primary endpoint, as it had a "significant effect" on the HVPG measurement in patients without varices.
It is the standard of care to look for varices in these patients, said principal investigator Stephen Harrison, M.D., medical director of Pinnacle Clinical Research in San Antonio. Therefore, this existing paradigm may be used to identify the patients without varices, who would benefit from this drug, he said.
But the potential of targeting this patient population is questionable—any type of serious liver disease can cause esophageal varices, with more than 90% of cirrhosis patients developing them, the Cleveland Clinic says.
This isn't the first time that GR-MD-02 has failed to impress. Last year, it missed the primary endpoint, as well as some secondary endpoints, in a phase 2a study of NASH patients with advanced fibrosis. And in 2014, Galectin shares sank on the results from a phase 1 trial in NASH fibrosis that it argued were positive.