11:33 AM
Jun 12, 2018
 |  BC Extra  |  Clinical News

After NASH readout, Galmed looks to Phase III

Galmed Pharmaceuticals Ltd. (NASDAQ:GLMD) gained $10.54 (150%) to $17.59 on Tuesday after it said data from the Phase IIb ARREST trial showed that once-daily oral Aramchol arachidyl amino cholanoic acid led to disease improvements in patients with non-alcoholic steatohepatitis. Galmed said the data "strongly support" a Phase III trial of the synthetic conjugate of cholic acid and arachidic acid.

On a secondary endpoint in ARREST, Galmed reported that the higher of two doses of Aramchol improved the proportion of patients with NASH resolution without worsening of fibrosis at week 52 vs. placebo (16.7% vs. 5%, p=0.0514). CMO Tali Gorfine acknowledged to BioCentury that the results were not statistically significant, but noted that the higher dose of the therapy did significantly improve the overall proportion of patients with NASH resolution (19.2% vs. 7.5%, p=0.0462).

The higher dose also led to a greater proportion of patients with a ≥1-point improvement in fibrosis score without worsening of NASH vs. placebo, although the results were also not significant (29.5% vs. 17.5%, p=0.211). Galmed said regulators would consider both secondary endpoints approvable in a pivotal trial, based on biopsy data. A lower dose of Aramchol did not lead to significant improvements on either endpoint.

ARREST evaluated 400 and 600 mg doses of Aramchol or placebo in 247 overweight or obese NASH patients with Type II diabetes or prediabetes. Galmed tested both potentially approvable biopsy endpoints based on lower numbers of evaluable patients within the study. Gorfine said a majority of the patients excluded from biopsy analyses were in Israel, where some patients were not permitted to have a second biopsy for regulatory reasons.

ARREST's primary endpoint measured the 600 mg dose's effect on change from baseline in liver triglycerides as measured by magnetic resonance spectroscopy (MRS) at week 52 vs. placebo. Galmed said low-dose Aramchol significantly reduced liver fat vs. placebo, but the higher dose did not (p=0.045 for 400 mg, p=0.0655 for 600 mg). Both doses of Aramchol significantly reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels vs. placebo.

Galmed plans to meet with regulators to discuss the design of a Phase III trial. Gorfine said the trial will likely evaluate two biopsy endpoints: NASH resolution without worsening of fibrosis, and fibrosis improvement without worsening of NASH. Those are the co-primary endpoints in a Phase III trial of Ocaliva obeticholic acid from Intercept Pharmaceuticals Inc. (NASDAQ:ICPT), the most advanced candidate to treat NASH. Gorfine did not give a specific time line for Galmed's trial.

In February, Aramchol failed in a Phase IIa trial to treat HIV-associated lipodystrophy and non-alcoholic fatty liver disease (NAFLD) (see BioCentury Extra, Feb. 14).

Galmed is the second company in the past two weeks to post big gains after a Phase II NASH readout. Madrigal Pharmaceuticals Inc. (NASDAQ:MDGL) gained 145% on May 31 after its MGL-3196 led to significant improvements vs. placebo in disease activity and disease resolution in a Phase II trial. MGL-3196 is a selective agonist of thyroid hormone receptor beta (see BioCentury Extra, May 31).

Tuesday's stock move pushed Galmed's market cap above $250 million.

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