Alnylam, Regeneron hit go on phase 2 trial of genetic NASH therapy after generating signs of efficacy

Alnylam and Regeneron have hit the gas on their RNAi nonalcoholic steatohepatitis (NASH) program, outlining plans to kick off a phase 2 clinical trial of the drug candidate after generating early evidence of efficacy.  

The candidate, ALN-HSD, is built on Regeneron’s linking of a loss-of-function variant in HSD17B13 to a reduced risk of chronic liver disease and progression from steatosis to steatohepatitis. Equipped with the insight, Alnylam deployed its technologies to develop a subcutaneously administered RNAi therapeutic with the potential to unlock the potentially large, but to date hard to crack, market for NASH therapies. 

Alnylam began testing how the candidate performs in healthy participants and, later, in NASH patients in 2020. The data have now matured to the point that the partners have the evidence to greenlight further development.

Across 20 subjects in the first two dose cohorts of NASH patients, the collaborators saw “robust” target knockdown, offering encouragement that the molecule works as expected, as well as liver enzymes and biopsy-derived nonalcoholic fatty liver disease activity scores that were lower over six months than in the four-participant control arm. The study wasn’t powered for statistical significance on the endpoints.

While the public will have to wait until an upcoming medical meeting to get a look at the data, Alnylam and Regeneron have seen enough to start preparing to move into phase 2. A trial is scheduled to start toward the end of the year. 

Regeneron registered a master protocol for a phase 2 study on last month. The trial features two studies, both of which will test two doses and use change in continuous quantitative liver fibrosis at Week 52 as their primary endpoint. lists the estimated enrollment at 300 subjects. 

Work on ALN-HSD is advancing alongside other NASH programs covered by the Alnylam-Regeneron deal. PNPLA3- and CIDEB-targeting therapeutics are moving toward first-in-human studies, giving the pair a portfolio of potential treatments for the liver disease.