The 61-patient study met the primary endpoint of improved physiologic liver function and secondary endpoints, which included established non-alcoholic steatohepatitis biomarkers, Hepion reported Monday.
Pictured: Illustration of a human body with the liver highlighted/iStock, magicmine
New Jersey-based Hepion Pharmaceuticals claimed a Phase II win in the potentially lucrative non-alcoholic steatohepatitis space Monday, releasing positive top-line data from its Phase II trial of oral drug candidate rencofilstat.
The 61-patient ALTITUDE-NASH trial, which relied on Hepion’s HepQuant SHUNT test to measure Disease Severity Index (DSI) scores across three doses—75 mg, 150 mg and 250 mg—met the primary endpoint of improved liver function.
The results were mixed, however, with the 250-mg dose yielding the most significant results with a 1.62-point decrease in the 18-patient cohort over four months. The mean decrease across all three doses was 0.55, but DSI scores rose in the middle cohort, raising questions about dose-dependent efficacy.
Study participants all had stage 3 or greater fibrosis based on the AGILE 3+ criteria. AGILE 3+ is calculated based on FibroScan fibrosis score, laboratory values (AST, ALT, platelets), and clinical parameters (age, sex, diabetes status). The study subjects had a baseline AGILE 3+ screening score of 0.53 or higher.
On an investor call Monday, Hepion Chief Medical Officer Todd Hobbs noted the significance of this specific patient population. “They’re very advanced and thus, more challenging to move the needle, if you will,” he said.
Hepion also claimed victories across several non-alcoholic steatohepatitis (NASH) biomarkers, including ALT, procollagen 3 C-terminal peptide, procollagen 3 N-terminal peptide and enhanced liver fibrosis. Hepion reported “robust” reductions in ALT and AST across all doses, with the greatest reductions seen at the 250-mg dose.
Safety and tolerability endpoints were also met, with Hepion reporting only one serious adverse event possibly related to rencofilstat. There were no deaths or hepatic decompensation events recorded in the trial, according to Hepion’s press release.
The Phase II trial was meant to confirm the positive results observed in Hepion’s 28-day Phase IIa AMBITION trial, an objective company executives on Monday’s call said was met. Hobbs said the information from all three doses will also be applied to Hepion’s 12-month Phase IIb ASCEND-NASH liver biopsy-based trial, which is currently recruiting.
A $24 Billion Opportunity
On the investor call, Hepion CEO Robert Foster put the number of adults with NASH in the U.S. at 20 million, with an estimated 30 million by 2030. NASH is a serious, progressive liver disease that can lead to cirrhosis, eventual liver failure, cancer and death.
The opportunity for companies in this space is substantial, with a March 2022 report by The Insight Partners predicting the NASH market will exceed $24 billion by 2028.
Hepion’s results follow a blow for competitor Intercept Pharmaceuticals, which on Friday failed to gain the support of the FDA’s Gastrointestinal Drugs Advisory Committee for its obeticholic acid (OCA) tablets for pre-cirrhotic liver fibrosis due to NASH.
In briefing documents released ahead of the advisory committee meeting, the FDA listed myriad safety concerns, with drug-induced liver injury topping the list. The external advisers appeared to agree with this assessment, with 12 of 16 saying the risks associated with OCA did not outweigh the potential benefits.
Other key players in this space include Akero Therapeutics, 89Bio, ChemomAb and Madrigal Pharmaceuticals. Madrigal’s resmetirom hit both primary endpoints and a secondary endpoint in the Phase III MAESTRO-NASH biopsy trial in December. Madrigal is widely perceived as the leader of the pack, with William Blair analyst Andy Hsieh saying in a note sent to BioSpace that resmetirom “will likely be the first approval in NASH.”
Heather McKenzie is a senior editor at BioSpace, focusing on neuroscience, oncology and gene therapy. You can reach her at heather.mckenzie@biospace.com. Follow her on LinkedIn and Twitter: @chicat08.
