Alfasigma bets up to $690M on GSK’s late-stage PBC itch drug ahead of FDA decision

The timing is notable as linerixibat is already under FDA review, and the agency has set a March 24, 2026 date for its approval decision. GSK has also submitted the drug for review in the EU, the UK, China and Canada, while China has granted the program priority review. The asset is not approved anywhere yet. 

For Alfasigma, the structure of the deal reflects how close linerixibat is to a potential launch. Beyond the $300 million upfront payment, GSK is eligible for another $100 million if the FDA approves the drug and a further $20 million tied to approvals in Europe and the UK, on top of up to $270 million in sales-based milestones. 

The drug targets one of the most burdensome symptoms of PBC: persistent internal itching caused by disrupted bile flow. In this autoimmune liver disease, bile acids build up in circulation and are believed to contribute to cholestatic pruritus, a symptom that can severely disrupt sleep and quality of life. GSK says pruritus affects up to 90% of people living with PBC, and standard first-line disease treatment does not reliably address it. 

Linerixibat works by inhibiting the ileal bile acid transporter, or IBAT, reducing bile acid reuptake in the gut. That mechanism is intended to lower the circulating mediators linked to itch. In the phase 3 GLISTEN study, GSK reported that linerixibat met its primary endpoint, showing a statistically significant reduction in itch over 24 weeks versus placebo. The study also hit key secondary endpoints, including improvements in itch-related sleep interference, with benefits emerging as early as week two. 

The safety profile was broadly in line with earlier studies and with the IBAT drug class. Gastrointestinal side effects were more frequent with active treatment, and diarrhea was the most common adverse event, though GSK said it was mostly mild; treatment discontinuation due to diarrhea occurred in 4% of patients on linerixibat versus less than 1% on placebo. 

The deal also fits neatly with Alfasigma’s strategy in hepatology. The Bologna-based company strengthened its liver franchise in November 2023 when it completed the acquisition of Intercept Pharmaceuticals, bringing Ocaliva into its portfolio. Ocaliva is a well-known PBC medicine, giving Alfasigma an established commercial footprint in the same disease area that linerixibat is targeting.

That backdrop helps explain why Alfasigma is positioning itself as a natural commercial home for the candidate. In the companies’ announcement, CEO Francesco Balestrieri said Alfasigma’s “deep hepatology expertise and strong global footprint” make it “uniquely positioned” to lead worldwide commercialization of linerixibat. GSK chief scientific officer Tony Wood said the agreement allows GSK to sharpen its focus on the next wave of liver disease programs while handing linerixibat to a partner with established PBC experience. 

For GSK, the transaction looks less like a retreat from liver disease than a portfolio reshuffle. The company has been leaning into larger hepatology opportunities, including bepirovirsen for chronic hepatitis B, which posted positive phase 3 results in January 2026, and efimosfermin, the Boston Pharmaceuticals asset GSK agreed to buy last year in a deal worth up to $2 billion, including $1.2 billion upfront. 

Commercially, linerixibat may have a window to establish itself. Mirum Pharmaceuticals is developing its own oral IBAT inhibitor, volixibat, for PBC-related pruritus, but that program remains behind linerixibat. Mirum has reported interim phase 2b data and says phase 3 topline data for its U.S. registrational program are expected in the second half of 2027. 

That means, if FDA reviewers clear linerixibat on March 24, Alfasigma could enter the market with what appears poised to become the first approved therapy specifically aimed at reducing cholestatic pruritus in PBC, rather than treating the underlying liver disease alone.