GSK is expanding its prospects in hepatology, paying $1.2 billion to acquire a drug that goes after a clinically validated liver target but with a dosing advantage that could give it a competitive edge against rivals further along in their development of therapies for the fatty liver disease MASH.
The agreement announced Wednesday brings GSK efimosfermin alfa, a Boston Pharmaceuticals drug that is ready for Phase 3 testing. In addition to metabolic dysfunction-associated steatohepatitis (MASH), GSK plans to develop the drug for alcohol-related liver disease. Both are forms of steatotic liver disease, in which fat buildup damages the organ.
MASH leads to inflammation and liver scarring, also called fibrosis. Though the history of MASH research is marked by many clinical trial failures and regulatory setbacks, the FDA last year approved the first MASH treatment, a once-daily pill called Rezdiffra from Madrigal Pharmaceuticals. This drug is a small molecule designed to activate a liver receptor called THR-beta.
Boston Pharma’s efimosfermin takes a different approach. The drug is an analog of fibroblast growth factor 21, or FGF21, a protein found in the body that regulates metabolic pathways for energy expenditure and fat metabolization. Native FGF21 has a half-life of one to two hours. Boston Pharma’s drug is a fusion protein engineered to last longer in the body. It’s administered as a once-monthly subcutaneous injection.
In a placebo-controlled, 24-week Phase 2 test that enrolled 84 MASH patients in stages 2 or 3 of the disease (stage 4 is liver cirrhosis), Boston Pharma reported results showing statistically signficant improvement in measures of fibrosis and resolution of MASH. The company also reported the drug showed a favorable safety and tolerability. The mid-stage data were presented last November during the American Association for the Study of Liver Diseases annual meeting.
Efimosfermin is joining a GSK pipeline that has a drug candidate that takes yet another approach to liver disease. GSK4532990 is a small interfering RNA drug designed to reduce expression of a particular liver enzyme that plays a role in the progression of fatty liver disease. In 2021, GSK paid Arrowhead Pharmaceuticals $120 million up front for rights to the siRNA drug. Under GSK, GSK4532990 has reached mid-stage clinical development in both MASH and alcohol-related liver disease (ALD). In GSK’s announcement of its latest deal, Chief Scientific Officer Tony Wood said efimosfermin’s ability to address fibrosis complements GSK4532990’s approach.
“Efimosfermin will significantly expand our hepatology pipeline and provide us the opportunity to develop a new potential best-in-class medicine with first launch expected in 2029,” Wood said. “It complements GSK‘990, also in development for ALD and MASH, offering GSK options to develop both monotherapy and potential combinations to improve patient outcomes.”
In a note sent to investors, Leerink Partners analyst said GSK’s acquisition of efimosfermin is the biggest deal in the MASH space since Allergan’s 2016 acquisition of Tobira Therapeutics for up to $1.7 billion. Smith said GSK’s acquisition of the Boston Pharma asset validates the MASH market opportunity, particularly for those developing FGF21 analogs.
Akero Therapeutics is currently in Phase 3 testing with an FGF21 analog, efruxifermin. In January, Akero reported Phase 2 results showing this once-weekly injectable drug reversed fibrosis after 96 weeks of treatment. To Leerink’s Smith, the closer competitor to the Boston Pharma drug could be 89bio’s pegozafermin, which is currently being evaluated in two Phase 3 tests in MASH (every two weeks dosing) and one in severe hypertriglyceridemia, or SHTG, (once weekly dosing). Smith acknowledged that once-monthly dosing of Boston Pharma’s drug poses less of burden to patients, but Leerink thinks the balance of efficacy, safety and patient convenience favors 89bio’s drug. This position is backed by more robust mid-stage data for the 89bio drug in both MASH and SHTG, he said.
Efimosfermin, formerly known as BOS-580, was originally developed by Novartis. Boston Pharma licensed global rights to the asset in 2020; financial terms were not disclosed. Beyond GSK’s upfront payment for efimosfermin, the deal puts Boston Pharma in line for up to $800 million in milestone payments. GSK is also responsible for milestone payments and royalties owed to Novartis.
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