Non-alcoholic steatohepatitis patients treated with the company’s efruxifermin saw significant improvements in liver fat and biomarkers of liver damage, fibrosis and cardiometabolic health.
Pictured: Kitty Yale and Tim Rolph, Akero Therapeutics/courtesy of Akero Therapeutics
Topline data from an expansion cohort of the Phase IIb SYMMETRY study showed that Akero Therapeutics’ lead candidate efruxifermin could safely and strongly reduce liver fat in patients with type 2 diabetes and liver fibrosis due to non-alcoholic steatohepatitis, the company announced Monday.
After 12 weeks of treatment, non-alcoholic steatohepatitis (NASH) patients treated with efruxifermin plus a GLP-1R agonist saw a 65% drop from baseline in hepatic fat fraction, as measured by the non-invasive magnetic resonance imaging-proton density fat fraction. Meanwhile, comparators treated only with the GLP-1R agonist saw a 10% reduction in liver fat. The treatment difference was statistically significant, according to Akero’s release.
Following efruxifermin treatment, 88% of participants achieved at least a 50% relative reduction in liver fat, while no patient in the GLP-1R-only arm reached such a threshold.
In an investor call Monday morning, Kitty Yale, chief development officer at Akero, said that “even though the Cohort D Phase IIb SYMMETRY study was not powered to demonstrate statistically significant differences” in efficacy endpoints, the combination of efruxifermin and a GLP-1R agonist led to “marked improvements” in key efficacy metrics.
Efruxifermin is an investigational drug that has been engineered to replicate the activity of the protein FGF21, an important player in multiple metabolic and cellular processes. By delivering sustained and balanced FGF21 signaling in the liver, efruxifermin can lower liver fat, ease inflammation, reverse fibrosis and improve insulin sensitivity and lipid levels in NASH, the company said.
Efruxifermin works beyond just NASH to regulate additional metabolic pathways and cellular processes, Tim Rolph, CSO and co-founder of Akero, told BioSpace earlier this year. “It not only improves [the] metabolic health of the liver but also appears to act directly to inhibit deposition of fibrotic tissue in the liver.”
SYMMETRY is a randomized, double-blinded and placebo-controlled study that enrolled 200 type 2 diabetes patients with biopsy-confirmed compensated cirrhosis due to NASH. In Cohort D, only patients who had been using a GLP-1R agonist for at least 90 days were eligible.
The main objective of Cohort D is to establish the safety and tolerability of Akero’s lead asset. To this end, the expansion cohort found efruxifermin to be generally well tolerated, with a side effect profile that was comparable to the GLP-1R agonist alone.
The most common adverse events associated with the candidate were grade 1 or 2 diarrhea, nausea, increased appetite and other gastrointestinal effects. Cohort D detected no drug-related serious toxicities.
SYMMETRY’s Cohort D also evaluated efruxifermin in terms of key fibrosis and liver injury indicators. Compared with GLP-1R alone, Akero’s candidate led to significant improvements in levels of biomarkers associated with liver damage and cardiometabolic health.
“We believe improvements to overall metabolic health will be a critical consideration to regulatory authorities as they review the overall risk-benefit profile of investigational NASH drugs,” Yale said during Monday’s call. The company is expecting the final readout from SYMMETRY in the fourth quarter of 2023 and is set to launch the Phase III SYNCHRONY trial in the second half of this year.
NASH Space Heats Up
Akero’s promising Monday data drop comes a few weeks after New Jersey–based Hepion claimed its own Phase II victory in NASH.
Early data from the company’s ALTITDE-NASH study showed that at a 250-mg dose, Hepion’s oral candidate rencofilstat led to a significant 1.62-point reduction in the Disease Severity Index, which measures liver function and physiology in NASH. Like efruxifermin, rencofilstat also induced significant improvements in biomarker including ALT and various procollagen peptides.
However, a few days before Hepion’s mid-stage win, the FDA’s Gastrointestinal Drugs Advisory Committee voted strongly against Intercept Pharmaceuticals’ obeticholic acid tablets, which the company is proposing as a treatment for pre-cirrhotic fibrosis due to NASH.
The panel of external experts flagged several safety concerns associated with the NASH hopeful.
In December 2022, Madrigal Pharmaceuticals also made major strides in NASH when it reported that its Phase III MAESTRO-NASH biopsy study met both of its primary and a key secondary endpoint. At both its 80-mg and 100-mg doses, Madrigal’s thyroid hormone receptor agonist resmetirom induced significantly better NASH resolution than placebo.
The company was planning to submit a New Drug Application for resmetirom in the second quarter of 2023, but has so far made no announcement of the submission.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
