Gatuzosiran

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.