Over the past few years, Akero Therapeutics has experienced high highs and low lows in its efforts to advance efruxifermin, an investigational drug for people living with metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis, or NASH). In 2022, results from the Phase 2b HARMONY study highlighted how efruxifermin improved fibrosis in 39% of people on the low dose and 41% of people on the high dose, compared to just 20% in those taking the placebo. However, the Phase 2b SYMMETRY trial later failed.

Now things are once again looking up, reports Nick Paul Taylor in Fierce Biotech. Taylor explains that the company recently published longer-term data from the HARMONY study. Previously, published data included results up to 24 weeks. The newest data covers 96 weeks of treatment. Some of the findings from the 96-week data include:

• 46% of people taking low-dose efruxifermin saw a 1-stage or more improvement in fibrosis without their condition worsening. In the high-dose cohort, this was 75%. Compare this to just 24% in the placebo group.
• 31% of people taking low-dose efruxifermin saw a 2-stage or more improvement in fibrosis without their condition worsening. In the high-dose cohort, 36% of people achieved that endpoint. Alternately, the placebo had a significantly lower response with just 3% of people achieving this endpoint.
• Efruxifermin was relatively safe and well-tolerated. 15 serious adverse reactions occurred, with three patients discontinuing treatment due to these reactions.

What is Efruxifermin?

Developed by Akero Therapeutics, efruxifermin:

has been engineered to mimic the biological activity of fibroblast growth factor 21 (FGF21), which regulates multiple metabolic pathways and cellular processes, [leverging] the whole body to improve metabolic balance. By delivering sustained and balanced signaling through FGF21’s receptors in liver and adipose tissue, efruxifermin has the potential to treat [MASH] by addressing all core drivers of disease progression.

About Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Metabolic dysfunction-associated steatohepatitis is an advanced stage of metabolic dysfunction-associated steatotic liver disease (MASLD). MASH is caused by excess fat cells in the liver. As this fat builds up, it causes liver inflammation, scarring, and damage. MASH can resemble liver disease caused by alcohol use. However, this condition occurs in people who drink very little or not at all. Rather, the damage in MASH is associated with obesity, diabetes, and high cholesterol. MASH affects up to 25% of people nationwide. It does not always get worse or become symptomatic. But if people do experience symptoms, these may include:

• Nausea and vomiting
• Losing weight without meaning to
• Abdominal pain
• Intense itchiness
• Appetite loss
• Fatigue and general weakness
• Jaundice (yellowing of the skin, eyes, and mucous membranes)
• Swelling of the legs and abdomen
• Mental confusion
• Easy bruising and bleeding
• An enlarged liver or spleen
• Portal hypertension