Hepion Pharmaceuticals is claiming success for its phase 2 nonalcoholic steatohepatitis (NASH) trial. But with the study lacking a control arm, relying on an investigational diagnostic and mostly only achieving significant results at the highest dose, plenty of questions about the candidate remain unanswered.
The clinical trial assigned 61 people with biopsy-confirmed NASH with histologic liver fibrosis stage 3 to take one of three daily doses of rencofilstat, a cyclophilin inhibitor. The primary efficacy endpoint looked at the change from baseline on a disease severity index (DSI), as measured by the HepQuant SHUNT Test. The test is an investigational diagnostic that measures the clearance of cholate to assess liver function.
Across the three doses, the DSI fell by 0.55 points over four months. Hepion identified the 1.62-point reduction in the 18-subject high-dose cohort as statistically significant, although the suggestion that efficacy increases in line with dose is undermined by the results from the middle dose. DSI worsened at the middle dose but numerically improved at the lowest dose.
Boehringer Ingelheim (PDF) and Intercept Pharmaceuticals (PDF) have used the HepQuant SHUNT Test in their studies, only one of which was in NASH. Of the 11 subjects who received 25 mg of Intercept’s obeticholic acid, 73% of people had a two-point or greater decrease in DSI. The rate in the high dose of Hepion’s trial was 61%.
Hepion also presented data on more established NASH biomarkers, reporting significant declines in the liver enzymes alanine and aspartate aminotransferase at all three doses. Other NASH drug developers have linked candidates to improvements in liver biomarkers only to fail to translate that promise into changes on the measures that are most important to the FDA and other regulators.
Another ongoing clinical trial will provide a clearer picture of whether Hepion has a chance of bringing rencofilstat to market. That study, the phase 2b ASCEND-NASH, is testing whether the same three doses of rencofilstat increase the proportion of subjects with improvement in fibrosis by at least one stage or NASH resolution without worsening of fibrosis compared to placebo.
The study has a completion date in 2025, per ClinicalTrials.gov. Hepion’s ability to keep going that long is in question, with the biotech’s latest quarterly results revealing “substantial doubt” about whether it can continue as a going concern without raising additional cash. News that Hepion was sharing the phase 2 data sent the stock up almost 50% in premarket trading but, with a market cap of $34 million before the surge, the biotech is still a minnow.