Elafibranor

The approval of Lynavoy comes a few days ahead of the FDA's March 24 decision target date. Alfasigma’s buzzer-beater bet on GSK’s rare liver disease prospect has paid off. After inking a deal worth up to $690 million to take on worldwide rights to the med last week, the FDA has doled out an approval a few days ahead of schedule.The drug, approved under the moniker Lynavoy, is an ileal bile acid transporter inhibitor that was designed to reduce multiple drivers of chronic itch. With the approval, the med is in position to reach the 89% of people with primary biliary cholangitis (PBC) who experience cholestatic pruritus, an often debilitating itching condition. The FDA signed off on the med a few days ahead of its March 24 decision target date based on GSK’s phase 3 Glisten trial, which showed Lynavoy significantly improved itch symptoms versus placebo over 24 weeks. Despite handing Lynavoy off to Alfasigma on March 9, the nod is still a milestone moment for GSK, as it represents “the first liver medicine from our pipeline to receive approval,” Kaivan Khavandi, M.D., Ph.D., GSK’s head of R&D for respiratory, immunology and inflammation, said in a company release.While “proud of the role” GSK played in discovering and developing the drug, the British pharma giant ultimately landed on Alfasigma as “the right partner to take this medicine forward” based on the Italian pharma’s experience in the PBC space, GSK’s chief scientific officer Tony Wood, Ph.D., explained at the time. Through the deal, GSK earned an upfront payment of $300 million plus an extra $100 million upon the FDA approval. The company is also in line for $20 million related to overseas regulatory approvals, plus up to $270 million in sales-based milestone payments and tiered double-digit royalties on net sales worldwide. The transaction has not yet closed, and Alfasigma is still “working closely with GSK,” it said in its own Thursday release. Alfasigma considers itself “uniquely positioned” to lead the worldwide commercialization of Lynavoy, given its “deep hepatology expertise and strong global footprint,” CEO Francesco Balestrieri said of the deal.  The company’s PBC experience stems from its 2023 $800 million buyout of Intercept Pharmaceuticals, which was inked after years of struggles for Intercept and its PBC med Ocaliva. After winning an accelerated approval for the treatment in 2016, Intercept’s attempts to grow the med with a full approval and with an expansion into metabolic dysfunction-associated steatohepatitis were both shot down multiple times. The drug fully sputtered out last year, when Intercept acquiesced to the FDA’s requests to withdraw Ocaliva from the market following continued safety concerns.Some six months later, Aflasigma will make its comeback in the PBC space through Lynavoy. With Ocaliva out of the race, the drug enters a market populated by Ipsen’s Iqirvo and Gilead Sciences’ Livdelzi, both of which hit the market in 2024.  Both companies have been recently reaping the benefits of the extra room in the PBC space, with Gilead reporting higher demand due to the Ocaliva withdraw and Ipsen touting growing momentum based on Ocaliva patient switches. Iqirvo garnered 77 million euros ($88.6 million) during the fourth quarter of 2025, while Livdelzi picked up $150 million.Lynavoy, meanwhile, is poised to corner a different core group of PBC patients with its cholestatic-pruritus-specific label. The condition can occur at any stage of the liver disease and has been “underestimated and overlooked for far too long, despite its significant impact on people living with PBC,” president of the PBCers Organization, Carol Roberts, noted in GSK’s release. 

GSK said Thursday that a drug it recently agreed to out-license to Alfasigma has been greenlit by the FDA to treat debilitating itch in patients with primary biliary cholangitis (PBC). Lynavoy (linerixibat), an oral IBAT inhibitor, becomes the first drug approved in the US for cholestatic pruritus linked to PBC (see – Spotlight On: Key PDUFA dates to watch in 1Q26).The filing was backed by the Phase III GLISTEN trial, which met its primary and key secondary endpoints, with Lynavoy demonstrating rapid, significant and sustained improvement over placebo at alleviating cholestatic pruritus and itch-related sleep interference.However, Lynavoy may struggle to compete in a market that has been reshaped by the introduction of PPAR agonists Livdelzi (seladelpar) from Gilead Sciences and Iqirvo (elafibranor) from Ipsen; both were approved for PBC in 2024 and have been shown to also significantly improve itch in PBC patients.Alfasigma made its entry into the PBC space through its 2023 takeout of Intercept Pharmaceuticals for around $794 million, gaining access to the FXR agonist Ocaliva (obeticholic acid) in the process. That treatment, however, was pulled from the US market last year at the FDA's request following years of safety concerns and regulatory scrutiny.GSK's licensing deal earlier this month included an upfront payment of $300 million from Alfasigma, along with another $100 million upon FDA approval. GSK is also eligible to receive $20 million linked to approvals of the drug in the EU and UK, where it is currently under review, and up to $270 million in sales-based milestones plus tiered double-digit sales royalties. Marketing applications have also been filed in China and Canada."For many patients, cholestatic pruritus remains a persistent, poorly addressed condition," Kaivan Khavandi, GSK's R&D head for respiratory, immunology and inflammation, said in a company release. "This is the first liver medicine from our pipeline to receive approval."However, with the Alfasigma deal, the UK drugmaker will be concentrating on other liver disease spaces it sees as larger commercial opportunities, such as hepatitis B and metabolic dysfunction-associated steatohepatitis (MASH).It is currently investigating the FGF21 analogue efimosfermin alfa (GSK6519754) in the Phase III ZENITH-1 and ZENITH-2 studies for MASH, while the siRNA oligonucleotide GSK4532990 is in Phase II development for MASH as well as for alcohol-related liver disease. Its most advanced candidate for hepatitis B infection is the antisense oligonucleotide bepirovirsen (GSK3228836), which is being tested in the Phase III B-Well 1 and B-Well 2 studies.