Efimosfermin wins key designations from FDA, EMA

A new therapy for metabolic dysfunction-associated steatohepatitis (MASH) has earned priority designations from regulators in both the US and Europe.

The drugmaker GSK announced late last month that its investigational liver therapy efimosfermin was granted Breakthrough Therapy status from the FDA and Priority Medicines (PRIME) designation from the European Medicines Agency. “These designations recognize efimosfermin’s potential and reflect GSK’s accelerating momentum in liver health,” said senior vice president Kaivan Khavandi, M.D., M.Res., Ph.D., M.B.A., M.R.C.P., in a press release. “We believe efimosfermin has the potential to significantly advance the standard of care by directly targeting liver fibrosis.

MASH leads to a buildup of scar tissue, and the company noted that fibrosis is an important predictor of adverse outcomes like cirrhosis, liver failure, and liver cancer. Efimosferin is a long-acting engineered variant of the hormone fibroblast growth factor 21 (FGF21), and is formulated as a once-monthly subcutaneous injection. The company says their therapy is designed to decrease liver fat, ameliorate liver inflammation and reverse liver fibrosis through the regulation of metabolic pathways.

Clinical trial data, including a phase 2 double-blind trial and an open-label extension trial found that patients with moderate (F2) to advanced (F3) fibrosis and cirrhotic (F4) fibrosis saw improvement when taking efimosfermin, compared with placebo. The therapy was also found to be well-tolerated, with mild and transient gastrointestinal adverse events being the most frequently reported adverse events.

The drug is important in part because it has the potential to serve a significant unmet need. A review published last year noted that there are currently only two therapies approved by the FDA to treat MASH and its predecessor, metabolic dysfunction-associated steatotic liver disease (MASLD). However, those therapies have indications limited to patients with moderate to advanced fibrosis. There are no approved therapies for patients with cirrhotic MASH, the company noted.

“MASH affects millions of people worldwide and is one of the leading causes of liver transplant in the US and Europe, but treatment options are limited for most and nonexistent for those with the most advanced form of the disease,” Khavandi noted.

Absent therapeutic intervention, lifestyle modifications such as weight loss and exercise are a main treatment strategy, at least for now.

Efimosfermin is currently the subject of the phase 3 ZENITH-1 and ZENITH-2 trials, which are studying the safety and efficacy of the therapy in patients with F2/F3 fibrosis. Phase 3 trials involving patients with F4 fibrosis are planned for later this year, the company said.

The two newly announced regulatory designations have different, but complementary, implications for the therapy. The FDA’s breakthrough designation means the agency believes the drug could represent a substantial improvement upon the currently available treatments for MASH. The designation makes the company eligible for enhanced guidance from the FDA in order to ensure the drug development process runs as efficiently as possible. It also entitles companies to fast-track review by the agency.

The EMA’s PRIME designation similarly will enable GSK to access early scientific advice from the agency in order to optimize the investigational process to ensure the necessary data are generated through the trial process for the agency to ultimately evaluate the therapy.

Efimosfermin was originally known as BOS-580 when it was being developed by Boston Pharmaceuticals. GSK completed an acquisition of the therapy from Boston Pharmaceuticals last year.