Akero Therapeutics has hit a home run, reporting statistically significant results in two key 96-week metabolic dysfunction-associated steatohepatitis (MASH) analyses to send its stock up about 100%. Analysts with Evercore ISI hailed the data as "transformational" in a note to investors.
The phase 2b trial of efruxifermin (EFX) missed its primary endpoint in 2023. However, while the FGF21 analog was no better than placebo after 36 weeks, Akero argued that deepening effects on fibrosis in cirrhotic MASH patients over time could enable the 96-week analyses to succeed.
All eyes were on two analyses: an intention-to-treat (ITT) review and a breakdown that excluded people who didn't have biopsies during Week 96.
Akero reported statistically significant improvements for its drug in both analyses. The ITT analysis, which treated all patients without Week 96 biopsies as failures, looked like a long shot for statistical significance going into the readout. The long gap between the primary and follow-up analyses, plus the need to have another biopsy, meant dropouts were likely and would be treated as failures in the ITT assessment.
Patients did drop out—the completer assessment included 47 fewer patients than the ITT cut—but the ITT analysis was still statistically significant.
In the ITT analysis, 29% of people on the high dose of EFX experienced reversal of cirrhosis without worsening of MASH. The figure compared to 12% for placebo in this analysis, and the p-value was 0.031.
In the completer analysis, 39% of patients on the high dose met the response criteria, versus 15% of the placebo arm. That p-value was 0.009.
At 36 weeks, Akero saw a 10 percentage point difference between the response rates for the study drug and placebo. The gap swelled to 24 percentage points by Week 96, adding to evidence that the effect of EFX on compensated cirrhosis increases over time.
"[Akero] is the first to show reversal of cirrhosis, a goal that has evaded the field until now. P3 is derisked," Evercore ISI analysts wrote in a note to clients. The analysts think Akero has "a good shot" at winning accelerated approval based on 96-week data and phase 3 data.
Akero dosed the first compensated cirrhosis patient in a phase 3 trial last year. The trial is one of three late-phase studies the company is running to evaluate the effects of EFX in different subpopulations of MASH patients.
Monday's readout, which included improvements in noninvasive measures of liver fibrosis and injury, sent the biotech’s share price up about 100% to almost $54 in premarket trading.
Akero’s share price last neared that level before the phase 2b primary endpoint miss in 2023. The stock jump potentially reflects both increased confidence Akero can succeed in phase 3 and speculation that it could be a buyout target.
In addition to the two main analyses, Akero shared a subgroup analysis to show how EFX performed in people who weren’t taking GLP-1 drugs such as Eli Lilly’s Zepbound and Novo Nordisk’s Wegovy. In this group of patients, the EFX and placebo response rates were 45% and 17%, respectively. Akero argued the result suggests “the observed reversal of cirrhosis was not attributable to GLP-1 therapy.”