MASH treatment efimosfermin wins new designations in US and EU
EMA grants PRIME status, FDA names liver disease drug a breakthrough therapy
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A once-monthly investigational therapy for metabolic dysfunction-associated steatohepatitis (MASH), called efimosfermin, has earned two new regulatory designations — one in the U.S. and the other in the European Union — for treating this severe form of steatotic liver disease.
Efimosfermin (formerly BOS-580) was awarded breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) for treating MASH. This status is designed to expedite the development and review of medicines for serious conditions that show potential for substantial improvement over available therapies.
The treatment candidate from GSK also was granted priority medicines (PRIME) status by the European Medicines Agency (EMA). A PRIME designation provides scientific and regulatory support for new treatments with the potential to address significant unmet medical need in EU nations.
The decisions to grant these regulatory statuses were based on data from a now-competed Phase 2 clinical trial (NCT04880031), which showed that efimosfermin was more effective than a placebo at reducing liver scarring, or fibrosis, and achieving disease resolution in people with MASH.
“These designations recognise efimosfermin’s potential and reflect GSK’s accelerating momentum in liver health,” Kaivan Khavandi, MD, PhD, senior vice-president and global head of respiratory, immunology and inflammation research and development and translational and development sciences at GSK, said in a company press release announcing the FDA and EMA decisions.
“We believe efimosfermin has the potential to significantly advance the standard of care [in MASH] by directly targeting liver [scarring],” Khavandi said.
MASH is the most advanced form of steatotic liver disease, occurring when the buildup of fat in the liver that marks the condition progresses to liver inflammation and scarring, or fibrosis. As liver fibrosis advances, the risk of life-threatening complications like liver failure and cancer increases, as does the need for a liver transplant.
MASH rates rising worldwide, with few treatment options
The number of MASH cases is increasing globally, studies in recent years have shown. This is particularly true among people with obesity and type 2 diabetes, which are known risk factors of the disease.
“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 non-existent for those with the most advanced form of disease,” Khavandi said.
Efimosfermin is a molecule that mimics the activity of the human fibroblast growth factor 21 (FGF21), a naturally occurring hormone that regulates metabolic pathways to reduce liver fat accumulation and liver inflammation.
In addition to its direct effects on the liver, FGF21 increases blood sugar (glucose) uptake in fat tissue — an important benefit for patients with type 2 diabetes, a condition marked by high glucose levels.
Given as an injection under the skin, efimosfermin has been engineered to overcome the short half-life of natural FGF21, extending it from about two hours to approximately 21 days. This allows for once-monthly dosing, compared with other FGF21-based treatments that require more frequent administration, the developer 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 non-existent for those with the most advanced form of disease.
The therapy’s safety and effeectiveness were evaluated in a U.S.-based Phase 2 trial. In the first part of the study, several efimosfermin dosing regimens were tested against a placebo in 102 obese adults with MASH. Three-month data showed that the therapy led to significant reductions in liver fat.
In fact, all patients receiving a monthly 300 mg dose achieved at least a 30% reduction in liver fat fraction, a level associated with a higher likelihood of fibrosis lessening.
In the second part of the study, the 300 mg dose was tested against a placebo for 24 weeks, or about six months, in 84 overweight or obese adults with MASH and moderate to advanced liver fibrosis.
These results showed that a significantly higher proportion of participants treated with efimosfermin achieved a measurable reduction in liver fibrosis without worsening of MASH compared with those on the placebo (45% vs. 21%).
In addition, 68% of patients in the efimosfermin group achieved MASH resolution without fibrosis worsening, compared with 29% in the placebo group — a statistically significant difference.
After six months, half of efimosfermin-treated patients achieved at least a 50% reduction in liver fat, compared with 6% of those in the placebo group, while nearly one-third (32%) reached normal liver fat levels versus 3% of those on the placebo, the data showed.
Efimosfermin showed benefits in trial for MASH patients
Efimosfermin also led to significant reductions in blood levels of liver injury markers and certain fatty molecules, as well as in glucose levels, particularly in participants with type 2 diabetes.
Those completing the study’s placebo-controlled part could enter its open-label extension portion, where they received efimosfermin for up to 48 weeks, or nearly one year.
Overall, the therapy’s benefits were maintained over time in patients initially treated with efimosfermin, while those who had received placebo showed similar improvements after switching to the treatment. Additionally, the therapy was generally well tolerated, with mostly mild and temporary adverse events, which included nausea, vomiting, and diarrhea.
Efimosfermin is now being investigated in MASH patients with moderate to advanced liver fibrosis in two Phase 3 trials: ZENITH-1 (NCT07221227) and ZENITH-2 (NCT07221188). Both studies are recruiting participants at multiple sites across the U.S.
Phase 3 studies in MASH patients with cirrhosis, or irreversible liver fibrosis, are expected to begin this year, per the developer.
