Akero Therapeutics, a leading contender in the nonalcoholic steatohepatitis (NASH) field, has encountered a setback as its FGF21 analog, efruxifermin (EFX), failed to achieve significant reductions in fibrosis among NASH patients with cirrhosis. This development sent Akero’s stock plummeting and had a ripple effect on a rival company’s share price.
The biotech made significant strides in the NASH arena over the past year, particularly in demonstrating the potential of EFX. In September 2022, Akero reported positive results linking EFX to fibrosis reduction in NASH patients with significant fibrosis but without cirrhosis. This was followed by promising data in June, suggesting that EFX could complement GLP-1 drugs used in obesity treatment.
However, the recent phase 2b SYMMETRY clinical trial aimed to establish EFX’s effectiveness in reducing fibrosis in individuals with compensated cirrhosis, but the trial failed to meet its primary endpoint.
After 36 weeks, 24% of patients on the high EFX dose showed at least a one-stage improvement in liver fibrosis without NASH worsening, compared to 14% in the placebo group. The low EFX dose had a slightly lower response rate at 22%. Neither dose demonstrated statistically significant superiority over placebo, although Akero did observe improvements in NASH resolution and liver injury markers.
This outcome led to a 66% drop in Akero’s stock price to $16.50 during premarket trading, essentially erasing gains made following the positive results from the previous year. The disappointment also impacted 89bio, a biotech firm developing a competing FGF21 analog, causing its share price to fall by 35% to $10.10 in premarket trading.
“Although no head-to-head comparative studies have been conducted, and despite the short treatment with EFX, the week 36 SYMMETRY results are the strongest data set reported to date in a placebo-controlled trial in the difficult-to-treat population of patients with cirrhosis due to NASH. Patients with cirrhosis have high levels of hepatic collagen and this takes time to resorb even though synthesis of collagen was rapidly and substantially reduced by EFX. I’m encouraged that statistically significant improvements on multiple measures of NASH pathogenesis were observed in EFX-treated patients. EFX shows promise for stabilizing and improving liver health for patients with cirrhosis, and I look forward to seeing the final SYMMETRY study results.”
– Stephen Harrison, M.D., founder and chairman of Pinnacle Clinical Research and Akero’s SYMMETRY study’s principal investigator
The potential for EFX to shine may become more apparent if the gap in fibrosis response rates between the treatment and placebo groups widens. Akero is also awaiting the SYMMETRY data before determining the duration of its follow-up phase 3 program for patients without cirrhosis, where EFX demonstrated fibrosis improvements by Week 24 in a previous study.
“We believe this analysis of the SYMMETRY study contributes to a growing body of evidence for EFX’s potential to benefit patients with NASH who are either cirrhotic or pre-cirrhotic. We set a high bar with the primary endpoint after only 36 weeks of treatment. Viewing these data in their totality, including a fibrosis improvement trend, reports of regression from cirrhosis to stage two fibrosis, statistically significant rates of NASH resolution, and statistically significant and sustained reductions in markers of liver injury and fibrosis after 36 weeks, we believe EFX has the potential to show additional improvements for patients after the long-term follow-up period is complete at Week 96.”
– Andrew Cheng, M.D., Ph.D., president and chief executive officer of Akero