Galmed Pharmaceuticals unveiled top-line results from a yearlong phase 2b study of its oral treatment for nonalcoholic steatohepatitis, demonstrating a statistically significant reduction in liver fat without worsening fibrosis.
The news boosted Galmed’s stock by over 250% in early trading, with the company saying in a statement that the study supports the advancement of once-daily Aramchol, an SCD1 modulator, into new clinical trials. The study had randomized doses of 400 mg, 600 mg and placebo in 247 overweight or obese patients with prediabetes or Type II diabetes, with NASH confirmed by biopsy.
The results just skimmed under the p-value of 0.05—the traditionally accepted watermark of statistical significance—with the 400-mg dose reducing liver fat in more patients compared to placebo with a p-value of 0.0450, measured by magnetic resonance spectroscopy.
The 600-mg dose, meanwhile, did not, with a p-value of 0.0655. However, an analysis of patients who showed 5% or more absolute change from baseline liver fat measurements, detected by MRS, showed a significant effect with the 600-mg dose in 47% of patients compared to 24.4% with placebo, and a p-value of 0.0279.
While noninvasive magnetic imaging might be the hoped-for option to support wider uptake of the drug, the study’s two biopsy-based endpoints may be what sets the stage for the phase 3 trial and eventual FDA submission. The company said it is planning to meet with regulators quickly to discuss the pivotal study design for Aramchol, which carries Fast Track status.
In one endpoint, more patients treated with 600 mg of Aramchol versus placebo achieved NASH resolution without worsening of fibrosis, at 16.7% versus 5.0% (p=0.0514), respectively, as well as NASH resolution more generally, at 19.2% compared to 7.5% (p=0.0462). In addition, the second biopsy endpoint showed a higher proportion of patients with at least a one-point improvement in fibrosis score without worsening of NASH.
In a note to investors, Jefferies analyst Michael Yee said the positive trends in the data look promising, and even though the phase 2b study did not hit statistical significance in regulatory endpoints, the drug could perform well in a larger trial. Additionally, Yee pointed out how the study’s placebo arm performed in line with previous phase 2 NASH clinical studies.
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“Some studies have shown an effect on NASH and some on fibrosis, while this study has shown an effect on both,” said principal investigator Vlad Ratziu, professor of hepatology at the Sorbonne Université and Hospital Pitié-Salpêtrière in Paris.
“Aramchol 400mg is probably sufficient for fat reduction but, biologically, a higher dose is needed for achieving more stringent histological endpoints such as NASH resolution and fibrosis reversal. NASH is a chronic disease with complex comorbidities and Aramchol's favorable safety and tolerability profile support long-term treatment,” Ratziu said.
Both doses also showed statistically significant reductions in live enzymes alanine transaminase (ALT) and aspartate transaminase (AST).
The progressive fatty liver disease could present a tricky, yet lucrative, upcoming market. It is estimated to affect 3% to 5% of the U.S. population and represents a fast-growing cause of liver cancer and transplants.
Several companies are racing to the clinic, including Bristol-Myers Squibb, Allergan, Shire and others. In addition, Jefferies’ Yee pointed toward upcoming pivotal NASH and cirrhosis data expected from Intercept Pharmaceuticals and Gilead Sciences in the first half of 2019.
Obstacles to widespread treatment adoption include the facts that diagnoses are mostly performed through invasive biopsies, with early-stage disease not presenting symptoms, at a time when excess liver fat can be reduced through diet and exercise.
Note: This story was updated with additional analysis.