GSK pays $1.2bn for liver drug as it culls TIGIT programme

 GSK decided to abandon a TIGIT-targeted drug for cancer this week, then immediately hatched a plan to replace it with a late-stage candidate for metabolic dysfunction-associated steatohepatitis (MASH).

The demise of iTeos Therapeutics-partnered TIGIT inhibitor belrestotug does not come as a complete surprise, given the well-documented challenges faced by companies developing this class of drug, although it does follow some promising results reported at last year's ESMO congress.

The company said it is canning belrestotug, and its $2 billion iTeos alliance, based on new data from phase 2 trials, "which did not meet the established efficacy criteria for continued development."

Enter efimosfermin alfa, described as a phase 3-ready, once-monthly injectable fibroblast growth factor 21 (FGF21) analogue with potential across steatotic liver diseases (SLD), including MASH and alcohol-related liver diseases (ALD).

The drug (formerly called BOS-580) is designed to prevent the characteristic fibrosis (scarring) seen with SLDs, which affect around 5% of the global population and have limited treatment options.

MASH is a form of non-alcoholic fatty liver disease (NAFLD) that affects between 6 million and 8 million people in the US alone and, for some time, has been billed as pharma's next big growth area. It is largely associated with obesity and an unhealthy diet and lifestyle, and is on the rise in industrialised nations, leading to estimates that it could present a market opportunity worth tens of billions of dollars a year.

GSK has agreed to pay $1.2 billion upfront to acquire rights to efimosfermin from Cambridge, Massachusetts-based Boston Pharmaceuticals, pledging another $800 million in milestone payments if the programme meets future objectives.

Efimosfermin was originally developed by Novartis, which stands to receive royalties on sales if it reaches the market.

GSK has said it is modelling a potential launch in 2029, and views the drug as a companion to GSK532990, a small, interfering RNA (siRNA) targeting HSD17B13, which is in phase 2 for both MASH (formerly known as NASH) and ALD.

Boston Pharma recently reported phase 2 results with efimosfermin in patients with moderate-to-advanced MASH, which showed the drug was able to reverse liver fibrosis and stop disease progression, while also improving other biomarkers like triglyceride and blood glucose levels.

GSK said that the drug could be used alongside other drugs being developed for MASH, including GLP-1 agonists. Novo Nordisk's GLP-1 drug semaglutide has also been shown to improve liver fibrosis in a phase 3 trial, setting up potential regulatory filings this year.

Currently, the only FDA-approved therapy for MASH is Madrigal Pharma's Rezdiffra (resmetirom), which got a green light last year.

"The FGF21 class has shown some of the most exciting data in MASH, including first-in-disease evidence of cirrhosis reversal, and efimosfermin has the potential to define a new standard-of-care with its monthly dosing and tolerability profile," said GSK's chief scientific officer, Tony Wood.

https://pharmaphorum.com/news/gsk-pays-12bn-liver-drug-it-culls-tigit-programme