Once-Monthly Efimosfermin Alfa in MASH With F2/F3 Fibrosis
Key Takeaways
- Adverse events were more common with efimosfermin than placebo, and most events were mild or moderate.
- The 24-week randomized, double-blind, placebo-controlled phase 2 study used 300 mg subcutaneous dosing every 4 weeks, with safety and tolerability as the primary endpoint.
- Gastrointestinal events were the most frequent and transient, and no clinically meaningful vital-sign changes or clinically significant grade 3 or higher laboratory abnormalities were reported.
The phase 2 randomized, double-blind, placebo-controlled trial took place at 34 clinical research study sites in the United States. Eligible adults were 18 to 75 years old, had a BMI of at least 27 kg/m2, and had biopsy-confirmed MASH with F2 or F3 fibrosis. Participants also needed a total NAS of at least 4, including at least 1 point each for steatosis, ballooning, and lobular inflammation.
Among 1171 people screened, 84 were randomized, with 43 assigned to efimosfermin alfa and 41 assigned to placebo. Randomization was 1:1 to 300 mg efimosfermin or placebo given by subcutaneous injection every 4 weeks for 24 weeks. 65 participants had evaluable week-24 biopsy results. All 43 participants in the efimosfermin group and 40 of 41 in the placebo group received at least one dose. Of those randomized, 44 were female and 40 were male, while 48 had F2 fibrosis and 36 had F3 fibrosis.
Most treatment-emergent adverse events were mild or moderate, with mild events reported in 24 of 43 efimosfermin recipients and 15 of 40 placebo recipients. Moderate events occurred in 18 of 43 and 14 of 40 participants, respectively, with no adverse events above grade 3 reported. Gastrointestinal events were the most frequent and were transient, appearing within the first few weeks of treatment.
Researchers observed no clinically meaningful changes in blood pressure or heart rate, no clinically significant grade 3 or higher laboratory abnormalities, and no deaths.