FDA considers noninvasive liver endpoint for clinical trials, sending MASH biotechs’ shares up

The FDA is considering using a noninvasive liver measurement as a surrogate endpoint for certain metabolic dysfunction-associated steatohepatitis (MASH) patients, a move that could speed up drug development in the space.

MASH is a severe form of fatty liver disease that can lead to severe scarring and impair liver function. Currently, the condition is mainly evaluated via multiple liver biopsies, which may miss the diffuse signs of the condition as it’s unevenly distributed across the organ.

Now, the FDA has accepted a letter of intent to qualify liver stiffness—as measured by transient elastography—as a reasonably likely surrogate endpoint in MASH patients with moderate to advanced fibrosis.

The letter was submitted by Céline Fournier, Ph.D., vice president of medical affairs at Echosens, a manufacturer of FDA-cleared, ultrasound-powered liver scanners. The submission includes letters of support from Eli Lilly, Boehringer Ingelheim and the company’s collaboration partner Novo Nordisk.

The document is the first of three steps in the drug development qualification tool process, a method that allows external submissions to help guide the agency in creating or revising such measures.

The liver stiffness biomarker can predict risk of death or liver-related events in MASH, according to the letter. The proposed noninvasive method could also provide a safer, more accessible way to track disease progression and responses to treatment. 

Sidestepping liver biopsies in novel MASH therapy development could also improve trial recruitment and help hurdle challenges tied to running adequately powered studies.

“This proposal represents an important step toward adopting noninvasive tests in drug development for MASH,” Frank Anania, M.D., director of hepatology and nutrition for the FDA’s Center for Drug Evaluation and Research, said in an August 27 release.

The news sent up the stocks of several MASH therapy developers, including Madrigal Pharmaceuticals, Viking Therapeutics, Inventiva and Altimmune.

“We see this as a significant positive for clinical development in the MASH space,” Leerink Partners wrote in a note this week, also citing the possibility that noninvasive measures may mitigate higher placebo responses tied to pathologist and biopsy sampling variability.

Though information around timing and potential implementation remain limited, Leerink said they were “increasingly encouraged by the FDA’s move away from biopsies toward non-invasive measures of efficacy.”