Akero Therapeutics has gathered early evidence that its nonalcoholic steatohepatitis (NASH) candidate plays nicely with GLP-1 receptor agonists. The phase 2b trial data suggest adding efruxifermin (EFX) to a GLP-1 drug drives deep drops in liver fat without causing safety problems.
Many NASH patients also have Type 2 diabetes or obesity. In another Akero trial, around 70% of subjects had (PDF) Type 2 diabetes and the average BMI was around 38, above the obesity threshold of 30. Based on the comorbidities of NASH patients, many of the people Akero hopes to treat with EFX may be taking a GLP-1 receptor agonist such as Novo Nordisk’s semaglutide to manage another condition.
That may be a good thing. Akero sees the mechanism of EFX, an insulin sensitizer, as complementary to that of GLP-1 receptor agonists, drugs that stimulate the secretion of insulin. To test the idea, the biotech enrolled 31 patients with non-cirrhotic NASH to a GLP-1-EFX combination expansion cohort.
All patients were on a stable dose of GLP-1 at baseline. Two-thirds of the subjects received EFX on top of the GLP-1 drug, with the rest taking placebo in addition to their existing therapy. After 12 weeks, liver fat fell by 65% in the EFX combination cohort, compared to a 10% drop in the GLP-1-placebo control arm.
The change is in line with the 64% decline that Akero saw in a slightly different patient population that took EFX as a monotherapy for 24 weeks. In the GLP-1 combination cohort, 88% of participants had a 50% or greater relative reduction in liver fat. The same proportion of patients had less than 5% liver fat, a level Akero classed as normalized, by Week 12. Both figures were 0% in the placebo arm.
Akero also shared data on a range of biomarkers. The readout links the addition of EFX, a fusion protein attached to a modified human FGF21, to improvements in liver stiffness, liver enzymes, lipids and other markers of liver and cardio-metabolic health.
In the small expansion cohort, Akero linked EFX to those improvements without sounding safety alarms. The tolerability profile was similar to that seen in earlier EFX monotherapy studies. Mild gastrointestinal events such as diarrhea and nausea were the most common adverse events in recipients of EFX. Nausea caused one patient to drop out of the trial. Another participant withdrew consent.
Akero, which is racing 89bio for the FGF21 opportunity, plans to share results from the rest of the phase 2b in the fourth quarter. The broader study is testing EFX as a monotherapy in sicker patients. Akero is planning to start a phase 3 trial in a different monotherapy population in the second half of the year.