Chasing Akero, 89bio reduces scarring in midphase NASH trial to hit primary goals, tee up phase 3

89bio is turning up the heat on Akero Therapeutics. In a phase 2b clinical trial, 89bio linked its FGF21 analog to reduced liver scarring in patients with nonalcoholic steatohepatitis (NASH) to stay hot on the heels of Akero’s rival drug candidate.

Akero provided early validation of the idea of using FGF21 analogs to treat NASH late last year in a phase 2b data drop that linked (PDF) its once-weekly candidate, efruxifermin, to reductions in fibrosis. The results set the bar for 89bio. While the nature of cross-trial comparisons makes it impossible to gauge exactly how well 89bio compares, the biotech has done enough to stay in the running. 

The primary analysis of the phase 2b clinical trial included 192 patients randomized across three doses of 89bio’s drug candidate, pegozafermin, and placebo. Participants in the top two dose cohorts received 44 mg every two weeks and 30 mg every week. 

Both cohorts beat placebo on the co-primary endpoints. At the 44 mg dose, 27% of patients had at least one-stage improvement in fibrosis without worsening of NASH, compared to 7% of their counterparts on placebo. The response rate at the 30 mg dose was 26%.

The difference between the treatment and control arms is nearly identical to that seen in Akero’s phase 2b trial, which linked the top dose of efruxifermin to a 21% placebo-adjusted improvement on its fibrosis endpoint. Akero’s study featured higher response rates than the 89bio trial across the board, with 20% of subjects in the placebo group meeting the fibrosis endpoint, but the same difference between the arms.

89bio’s results on the second co-primary endpoint are less compelling. All three pegozafermin arms beat placebo in terms of the proportion of patients with NASH resolution without worsening of fibrosis, but the response rate in the small low-dose cohort, 37%, was highest. In the 44 mg arm, 26% of subjects met the endpoint, compared to 2% of people on placebo.

Again, the figures in the Akero study were higher across the board, with 15% of patients in the control group meeting the endpoint, but for this measure the placebo-adjusted difference was higher, too. At the high dose, 76% of recipients of efruxifermin met the endpoint. 

On the safety front, 89bio reported one drug-related serious adverse event. The event, uncomplicated pancreatitis, affected a patient who received a single dose and quickly resolved. The hits on the primary endpoints and clean safety profile led 89bio to outline plans to move into phase 3. If the rival drugs perform comparably in their pivotal programs, the less frequent dosing of pegozafermin could give 89bio an edge.

Investors certainly appeared pleased, sending 89bio's shares up 26% to above $13.80 in premarket trading.