After missing the primary endpoint in the Phase IIb SYMMETRY trial, Akero Therapeutics’ lead molecule, efruxifermin, showed greater improvements after 96 weeks of treatment in an advanced disease population.
After failing to meet the primary endpoint in the Phase IIb SYMMETRY study, Akero Therapeutics rebounded Monday with positive long-term data for its lead candidate, efruxifermin, in metabolic dysfunction-associated steatohepatitis.
At 96 weeks, efruxifermin, an engineered Fc-FGF21 fusion protein that mimics the endogenous activity of fibroblast growth factor 21 (FGF21), showed a 24% benefit on fibrosis reduction over placebo in patients with liver cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH), according to Akero. Patients receiving efruxifermin at the highest dose of 50 mg saw a 39% improvement in liver fibrosis compared with the placebo group , which saw a 15% improvement. In an interesting twist, a subgroup of patients confirmed to not be taking GLP-1 medications saw a 45% improvement versus 17% among this subgroup in the placebo arm.
In an investor note Monday, Jefferies analysts called the data a “homerun” and said it “further boosts confidence in Phase III which is now very de-risked.”
Shares of Akero ascended by 115% in early Monday trading upon the news.
MASH-associated cirrhosis patients “face a poor prognosis,” Catriona Yale, chief development officer at Akero, said on an investor call Monday, noting a 50% five-year mortality rate for these patients. Individuals with advanced liver scarring have few treatment options, generally being forced to eventually wait for a liver transplant, she said.
The benefit for patients taking efruxifermin seemed to increase over time and with dosage, Yale added. “Longer dosing matters for this drug.”
The long-term data appear to bear out this statement. In October 2023, Akero reported that after 36 weeks of treatment, 22% of patients treated with the 28-mg dose of efruxifermin saw at least a one-stage improvement in liver fibrosis with no MASH worsening, whereas 24% of those given the higher 50-mg dose met this endpoint.
The MASH space saw its first approved treatment in March 2024, when the FDA greenlit Madrigal Pharmaceuticals’ Rezdiffra to treat the disease. Rezdiffra, however, is intended for patients with less advanced liver disease (stages 2 and 3), while efruxifermin is targeting the more advanced stage 4 population.
Mazen Nourredin, the principal investigator of the SYMMETRY study, noted the positive results in this advanced patient population.
“Until today, we’ve not had the prospect of an effective treatment for compensated cirrhosis due to MASH, which is associated with high rates of short-term morbidity and mortality,” Nourredin said in a statement.
