Ex-Novartis NASH drug clears clinical test, fueling Boston's pursuit of Akero, 89bio

Boston Pharmaceuticals has posted early evidence that its ex-Novartis candidate works in nonalcoholic steatohepatitis (NASH). But with Akero Therapeutics and 89bio taking rival drugs to the cusp of phase 3, it's unclear whether the biotech can differentiate BOS-580 from more advanced candidates.

The Massachusetts-based biotech reported phase 2a data on the long-acting fibroblast growth factor 21 (FGF21) analog on Wednesday. Investigators randomized 102 patients with phenotypic NASH to receive placebo or subcutaneous doses of BOS-580 once or twice a month. Boston designed the study to primarily look at safety, tolerability and dose-response but included exploratory efficacy endpoints. 

At least 70% of people who took 150 mg or more of BOS-580 a month for 12 weeks had a 50% or greater reduction in liver fat, compared to 3% of their counterparts on placebo. And participants who received 300 mg of the drug a month had at least a 45% reduction on alanine transaminase (ALT), a liver injury biomarker. Boston also linked the 300-mg dose to a 30% reduction in the soluble marker of fibrosis PRO-C3.

“Today’s findings strengthen our belief that BOS-580 has the potential to play an important role as a once monthly treatment available to physicians who treat patients suffering from NASH. We are looking forward to further accelerate the development of our molecule towards pivotal trials and ultimately registration,” Boston CEO Sophie Kornowski said in a statement.

Other companies have already shown similar changes in larger, later-stage clinical trials. Last year, Akero validated the use of FGF21 to treat NASH in a phase 2b clinical trial. 89bio delivered phase 2b data on its own FGF21 candidate in March to stay tucked in behind Akero in the race to market.

The phase 2b trials were primarily designed to show whether the candidates can reduce scarring, the goal they will need to achieve to win approval, but also looked at the same biomarkers as the Boston study did. Akero reported an up to 64% reduction on liver fat and 47% decline in ALT after 24 weeks, while 89bio linked its candidate to an up to 54% reduction in liver fat and 42% decline in ALT.

Standard caveats about the unreliability of cross-trial comparisons and the gaps in the data in Boston’s top-line release make it impossible to gauge how BOS-580 compares to its rivals. If Boston is unable to differentiate its candidate based on efficacy, there may be scope for it to carve out a niche by providing a safer, more tolerable or more convenient treatment.

Boston shared a snapshot of safety and tolerability data in its statement, revealing that gastrointestinal effects were the most common adverse events and that the rates of discontinuation due to treatment-emergent adverse events were similar in the BOS-580 and control arms. In terms of convenience, Boston is considering a less frequent dosing schedule—once monthly—than its rivals. 

Novartis decided to cut its ties to the candidate in 2020 before its broader retreat from the NASH space and only months after Akero provided early evidence that FGF21 may be the key to treating the disease.