Boston Pharmaceuticals has linked its metabolic dysfunction-associated steatohepatitis (MASH) prospect to improved outcomes in a midphase trial, positioning the biotech to advance the ex-Novartis candidate toward late-stage development in 2025.
The study tested efimosfermin alfa, formerly known as BOS-580. Like Akero Therapeutics’ efruxifermin and 89bio’s pegozafermin, the molecule is an FGF21 analogue. The twist is Boston has modified its fusion protein to extend its half-life. Efruxifermin and pegozafermin are given weekly. Boston gave efimosfermin monthly to the MASH patients with stage F2/F3 fibrosis in its phase 2 trial.
After 24 weeks, 14 of the 31 patients who received 300 mg of efimosfermin had a one stage or greater improvement in fibrosis without worsening of MASH, compared to 7 of the 34 people on placebo. The difference between the proportion of people who met the criteria, 45.2% and 20.6%, was statistically significant.
The data are in the same ballpark as the results for Boston’s weekly rivals. In a larger, phase 2b trial, up to 41% of patients taking Akero’s efruxifermin met the response criteria at Week 24, compared to 20% of people on placebo. The figures in 89bio’s phase 2b trial were 27% for pegozafermin and 7% for placebo. The placebo-adjusted result is bigger in Boston’s trial, but that edge could evaporate in larger trials.
Some phase 3 trials use the improvement in fibrosis without worsening of MASH as a primary endpoint. Boston also reported data on another widely used phase 3 endpoint, namely MASH resolution without worsening of fibrosis. In the efimosfermin arm, 67.7% of participants met the criteria, versus 29.4% of people on placebo. Again, the result looks competitive compared to other FGF21 analogues.
Boston said the discontinuation rate because of adverse events was low in the efimosfermin cohort. The incidence of gastrointestinal side effects and injection site reactions was low, too, according to the biotech.
Investigators are continuing to track the phase 2 patients in an open-label extension. Boston already has its eye on the next step, with the biotech outlining plans to move into late-stage development next year.
The program is central to Boston's prospects. When the biotech emerged with a $600 million financing commitment in 2015, the team had plans to build a large portfolio of programs. By 2020, that strategy was in full swing, with Boston boasting a pipeline that featured almost 10 clinical programs and a clutch of preclinical projects. Today, Boston’s public pipeline has two assets. Efimosfermin is the most advanced.
The first approved drug for MASH was signed off by the FDA earlier this year in the form of Madrigal Pharmaceuticals' Rezdiffra in what is believed to kick-start a major new market. It was a long time coming, with many Big Pharmas and biotech trying and failing in the clinic to produce an effective MASH med that was also safe.
Now, there are many more strong contenders on the horizon, not least coming from new GLP-1 drugs from Novo Nordisk and Eli Lilly, which have both been testing their obesity/diabetes franchises in MASH in the hope of adding yet another new use to these blockbuster drugs.