Up to 67% of patients achieve MASH resolution at 36 weeks with efruxifermin

Key takeaways:

• At week 36, 22% and 24% of patients in efruxifermin 28 mg and 50 mg groups achieved fibrosis improvement without worsening of MASH.
• Resolution of MASH occurred among 67% and 60%, respectively.

BOSTON — Treatment with efruxifermin resulted in “clinically meaningful” but not yet statistically significant benefit at 36 weeks in cirrhotic patients with metabolic dysfunction-associated steatohepatitis, according to late-breaking data.

“FGF21 is an endogenous metabolic hormone that plays an important role in glucose and lipid homeostasis,” Stephen Harrison, MD, COL (ret.), FAASLD, founder of Pinnacle Clinical Research in San Antonio, said at The Liver Meeting. “Efruxifermin is an FGF21 agonist that has previously demonstrated significant benefit on NASH resolution and fibrosis improvement in a noncirrhotic cohort of patients with significant fibrosis.”

Harrison continued: “Given the high unmet medical need in NASH cirrhosis, it warrants study with this particular mechanism.”

The phase 2b, randomized, double-blind, placebo-controlled SYMMETRY study enrolled 181 patients with well-compensated F4 MASH, formerly known as NASH, and type 2 diabetes or two of the four components of metabolic syndrome.

Participants received once-weekly subcutaneous placebo (n = 61), efruxifermin 28 mg (n = 57) or efruxifermin 50 mg (n = 63) for 96 weeks.

The primary studied endpoint was the proportion of patients who achieved at least one stage of fibrosis improvement with no worsening of MASH, based on liver biopsy obtained at week 36. Key secondary endpoints included MASH resolution, fibrosis markers, lipoproteins, glycemic control, weight change and liver injury markers.

“Importantly, all patients had biopsy-proven compensated cirrhosis with definitive NASH or cryptogenic cirrhosis presumed secondary to NASH,” Harrison noted. “In fact, 20% of the cohort was cryptogenic.”

According to results, 155 patients completed week 36 and 153 biopsies were collected.

At week 36, 22% patients in the efruxifermin 28 mg group and 24% in the 50 mg group achieved the primary endpoint of fibrosis improvement without worsening of MASH compared with 14% of patients in the placebo group. Resolution of MASH at this time point was reported in 67% and 60%, respectively, vs. 26%.

Among a subgroup of patients with cirrhosis diagnosed for at least 6 months or baseline cryptogenic cirrhosis, the primary endpoint was achieved by 10% in the efruxifermin 28 mg group and 22% in the 50 mg group vs. 3% on placebo.

Results also showed efruxifermin correlated with “significant improvements” in noninvasive markers of liver injury and fibrosis measured by enhanced liver fibrosis score, Pro-C3, liver stiffness and FibroScan-aspartate aminotransferase score.

Treatment-emergent serious adverse events occurred among 16%, 10% and 10%, respectively, and events leading to discontinuation occurred among 9%, 13% and 3%. The most frequent drug-related adverse events were diarrhea (18%, 30% and 15%), nausea (19%, 29% and 11), increased appetite (12%, 27% and 5%) and injection site erythema (14%, 21% and 8%).

“In this challenging, well-compensated cirrhotic population, a clinically meaningful but not yet significant clinical benefit was seen as early as 36 weeks,” Harrison said. “The totality of the data to include markers of liver injury and fibrosis suggest overall improvement of liver health at this early time point. There is a favorable safety and tolerability profile consistent with prior studies in noncirrhotic patients.”

He continued: “Patients will remain on treatment and a repeat liver biopsy will be assessed at the 96-week time point.”