Monthly efimosfermin offers ‘rapid, meaningful’ improvement for MASH, related fibrosis

Key takeaways:

• Nearly half of patients with MASH treated with once-monthly efimosfermin 300 mg saw fibrosis improvement without worsening of MASH at 24 weeks.
• MASH resolution without worsening fibrosis was reported in 67.7%.

SAN DIEGO — Patients treated with once-monthly efimosfermin 300 mg achieved significant improvements in metabolic dysfunction-associated steatohepatitis resolution and fibrosis at 24 weeks, according to late-breaking data.

“Metabolic dysfunction-associated steatohepatitis represents a significant unmet medical need, as it is one of the leading causes of liver transplantation in the U.S.,” Mazen Noureddin, MD, MHSc, professor of medicine at Houston Methodist Hospital and director of the Houston Research Institute, told Healio. “Despite its prevalence, effective therapeutic options are limited, particularly for patients with advanced fibrosis.”

He added: “Efimosfermin alfa (BOS-580, Boston Pharmaceuticals), a long-acting, once-monthly [fibroblast growth factor 21] analogue, has the potential to provide meaningful clinical benefits to patients by targeting liver fibrosis and improving metabolic health, both of which are critical aspects of MASH management.”

In the phase 2 trial presented at The Liver Meeting, Noureddin and colleagues assessed the safety and efficacy of efimosfermin vs. placebo in 84 patients (52.4% female; mean age, 54 years; mean BMI 37.3 kg/m²) with biopsy-confirmed MASH and stage 2 or 3 fibrosis; more than half (57%) of patients had type 2 diabetes and 43% had stage 3 fibrosis. Patients were randomly assigned 1:1 to receive once-monthly subcutaneous efimosfermin 300 mg (n=43) or placebo (n=41) for 24 weeks.

The researchers also investigated whether treatment with efimosfermin improved fibrosis by at least one stage without worsening of MASH, resolved MASH without worsening of fibrosis alongside a 2-point improvement in nonalcoholic fatty liver disease score (NAS) and if the drug could achieve a composite endpoint of fibrosis improvement at least one stage with MASH resolution.

Noureddin reported that patients who received once-monthly efimosfermin compared with placebo met the study endpoints with “high statistical significance and numerical value.”

According to biopsy analysis results of 34 efimosfermin-treated patients vs. 31 placebo-treated patients, the proportion of patients who improved by at least one fibrosis stage without worsening of MASH was higher among those receiving efimosfermin vs. placebo (45.2% vs. 20.6%; P = .038). Similarly, MASH resolution without worsening of fibrosis was achieved by a greater proportion of those receiving efimosfermin vs. placebo (67.7% vs. 29.4%; P = .002).

Further, the researchers observed that a significantly higher proportion of patients treated with efimosfermin achieved MASH resolution with at least a 2-point improvement in NAS without worsening of fibrosis compared with those given placebo (67.7% vs. 20.6%; P < .001). The composite endpoint also was achieved by a greater proportion of efimosfermin-treated patients (38.7% vs. 17.5%; P = .066).

“The once-monthly administration of efimosfermin in this study demonstrated a highly manageable tolerability profile, with low discontinuation rates due to adverse events, and an overall low incidence of nausea, vomiting, diarrhea and injection site reactions,” Noureddin told Healio.

However, the researchers noted that two patients on efimosfermin discontinued treatment due to low- grade adverse events and one patient experienced a treatment-related grade 3 serious adverse event.

According to Noureddin, those on efimosfermin achieved “statistically significant improvements” in biomarkers, including, hepatic fat measured by MRI-proton density fat fraction, measures of glucose control in those with type 2 diabetes, the enhanced liver fibrosis test and liver enzymes correlated with liver inflammation.

“Efimosfermin offers a compelling profile as a potential treatment for people diagnosed with moderate-to-advanced stage liver disease with rapid and meaningful improvements observed in both liver histology and metabolic markers,” Noureddin told Healio. “Efimosfermin could address critical gaps in the treatment of MASH given there is an urgent need for effective and convenient liver-targeted, anti-fibrotic treatments that can prevent complications without increasing the risk of cardiometabolic issues.”

Given to these promising results, Noureddin noted that the next step in research will be to collect long-term data for efimosfermin up to 48 weeks, as well as pharmacokinetic and safety data, among patients with cirrhosis or stage 3 fibrosis.