GSK prepares Mash Drug for Metastatic Hepatitis through Stage 3 of $1.2B
GSK is expanding its hepatology prospects, paying $1.2 billion to acquire drugs that follow clinically validated liver targets, but with a dosing advantage that could give it a further competitive advantage with its competitors in the development of slurry therapy for fatty liver disease.
The agreement announced Wednesday that it would be GSK Efimosfermin Alfa (Boston Pharmaceutical Drug Preparation for Phase 3 Tests). In addition to metabolic dysfunction-related steatohepatitis (MASH), GSK plans to develop drugs for alcohol-related liver diseases. Both are forms of fatty liver disease, where fat accumulation can damage the organs.
Mashed potatoes cause inflammation and liver scars, also known as fibrosis. Although the history of MASH research is characterized by many clinical trial failures and regulatory setbacks, the FDA approved last year the first MASH treatment for MADRIGAL PHARMACETICALS, a type of Rezdiffra that used to be a daily rezdiffra. The drug is a small molecule designed to activate a liver receptor called Thr-beta.
Efimosfermin in Pharma, Boston, took another approach. The drug is an analog of fibroblast growth factor 21 (FGF21), a protein found in the body that regulates energy consumption and fat metabolism of metabolic pathways. The half-life of local FGF21 is one to two hours. The Boston Pharma drug is a fusion protein that lasts longer in the body. It is used as a subcutaneous injection once a month.
In a 24-week 2-week Phase 2 test, 84 patients with MASH were recruited in the 24-week Phase 2 (Stage 4 is liver cirrhosis), and the results reported by Boston Pharma show that there are statistically significant measures to improve fibrosis and MASH resolution. The company also reported that the drug showed good safety and tolerance. In November last year, at the annual meeting of the American Association for Research on Hepatic Diseases, the interim data were introduced in November last year.
Efimosfermin is joining the GSK pipeline, which has drug candidates that take another approach to address liver disease. GSK4532990 is a small interfering RNA drug designed to reduce the expression of specific liver enzymes and plays a role in the progression of fatty liver disease. In 2021, GSK paid $120 million from Arrowhead Pharmaceuticals to obtain rights to siRNA drugs. Under GSK, GSK4532990 has achieved intermediate clinical development in both MASH and alcohol-related liver disease (ALD). In the news that GSK announced its latest deal, Chief Science Officer Tony Wood said efimosfermin's ability to solve fibrosis complements GSK4532990's approach.
“efimosfermin will greatly expand our hepatology pipeline and provide us with the opportunity to develop new potential first-class drugs and the first launch expected in 2029,” Wood said. “It complements GSK’990, which is also under development of ALD and MASH, providing GSK options to develop monotherapy and potential combinations to improve patient outcomes.”
GSK's acquisition of Efimosfermin is the largest deal in MASH Space since Allergan's acquisition of Tobira Therapeutics in 2016, with a maximum of $1.7 billion, analysts at Leerink Partners said in a note sent to investors. Smith said GSK's acquisition of Boston's Pharma assets confirmed the MASH market opportunity, especially for those developing the FGF21 analogue.
Akero Therapeutics is currently undergoing 3-stage testing using the FGF21 analog Efruxiferin. In January, Akero reported the phase 2 results, showing that the once-weekly injectable drug reversed fibrosis after 96 weeks of treatment. For Leerink's Smith, a competitor closer to the Boston drug drug may be PEGOZAFERMIN of 89BIO, currently undergoing two phase 3 tests in MASH (dosed every two weeks), one being evaluated in severe hypertriglyceridemia or SHTG, or (dose once a week). Smith acknowledged that the burden on patients with a monthly dose of Boston medication was reduced, but Leerink believes that the balance of efficacy, safety and patient convenience favors 89bio's medication. He said the position is supported by stronger interim data on 89BIO drugs in MASH and SHTG.
Efimosfermin, formerly known as BOS-580, was originally developed by Novartis. Boston Pharmaceuticals acquired global rights to the asset in 2020; financial terms are not disclosed. In addition to the upfront payments made by GSK to Efimosfermin, the transaction also puts Boston Pharmaceuticals at a milestone payment of up to $800 million. GSK is also responsible for the milestone payments and royalties owed to Novartis.
Image: Sebastian Kaulitzki/Science Library, Getty Images
