Alfasigma claims early FDA nod for ex-GSK liver drug

The FDA has approved Alfasigma's primary biliary cholangitis (PBC) therapy linerixibat, just days after the company licensed it from GSK in a deal worth up to $690 million.

The US regulator confirmed approval of IBAT inhibitor linerixibat, under the Lynavoy trade name, as a treatment for cholestatic pruritus in PBC on 17th March. PBC is a chronic, progressive autoimmune liver disease that can cause relentless, debilitating itching.

Alfasigma, a privately-held Italian drugmaker, has not yet indicated what its launch and pricing plans are for Lynavoy, which was cleared by the FDA a few days before the action date for its review. The drug has also been filed for approval in the EU, UK, China, and Canada, with additional decisions expected before the end of this year.

Analysts have suggested that Lynavoy could make peak sales in the region of $500 million a year, which would be a relatively modest tally for GSK, but make it a big product for Alfasigma, whose sales were €1.87 billion in 2024. Alfasigma paid $300 million upfront for rights to the drug, with GSK also due to receive another $100 million on FDA approval.

The approval comes on the back of the GLISTEN trial, which involved 238 patients with documented PBC and moderate to severe itching, with linerixibat compared to placebo over 24 weeks.

The primary endpoint was the change from baseline in monthly itch score and data reported at last year's European Association for the Study of the Liver (EASL) conference. The data revealed that linerixibat users recorded an average placebo-adjusted improvement of 0.72 points on a 10-point itch scale for the worst itch, measured using the WI-NRS scale, with significant improvements seen within the first two weeks.

Alfasigma built a position in PBC when it acquired Intercept Pharma in 2023 for $800 million, giving it ownership of the latter's Ocaliva (obeticholic acid) therapy for the disease, which, for almost a decade, was the only option for patients after first-line treatment with ursodeoxycholic acid (UDCA).

Ocaliva was taken off the market last year, however, after failing a confirmatory study and a review that suggested its benefits no longer outweighed its risks.

Thankfully for patients, treatment options for PBC have expanded in the last couple of years, with FDA approvals in 2024 for Ipsen/Genfit's dual PPAR alpha/delta agonist Iqirvo (elafibranor) and Gilead Sciences' PPAR-delta activator Livdelzi (seladelpar), and Lynavoy now offers an additional treatment option with a new mechanism of action.

Competition could also be coming soon from Mirum Pharma, whose rival oral IBAT inhibitor volixibat is in late-stage clinical testing.