Six months after withdrawing a drug from the U.S. market for a rare liver disease, Alfasigma is reaffirming its commitment to the disorder by paying $300 million for rights to a GSK drug candidate on track to receive an FDA decision in this indication in late March.
The GSK drug, linerixibat, was developed as a treatment for pruritus, or severe itching, caused by primary biliary cholangitis (PBC). The deal terms announced Monday give Alfasigma global rights to the drug, bringing another product to a portfolio that includes other liver disease therapies.
In PBC, disrupted flow of bile from the liver leads to excess bile acids in circulation. These bile acids are thought to lead to cholestatic pruritus, internal itching that cannot be relieved by scratching. The severe itchiness can disturb sleep and impair a patient’s quality of life.
Linerixibat, formerly known as GSK2330672, is a small molecule inhibitor of ileal bile acid transporter (IBAT), a transporter protein that regulates bile acid levels. Blocking IBAT is intended to reduce levels of bile acid in the blood associated with the severe itching caused by PBC. IBAT inhibition already has validation from Ipsen and Mirum Pharmaceuticals drugs with FDA approvals for treating pruritus caused by other rare liver disorders.
Alfasigma had taken a different approach to PBC with Ocaliva, a small molecule designed to bind to and activate FXR, a receptor that plays a role in regulating bile acid. This drug was initially developed and commercialized by Intercept Pharmaceuticals, which received accelerated approval for the daily pill in 2016 for the treatment of PBC. But Intercept failed in its efforts to expand the drug’s label to the more prevalent fatty liver disease MASH. The regulator also turned down Intercept’s application seeking full regulatory approval in PBC.
Intercept’s acquisition by Bologna, Italy-based Alfasigma in 2023 did not end Ocaliva’s woes. In 2024, the FDA issued a safety communication about liver cirrhosis risks associated with the drug. Soon after, the European Commission revoked the product’s conditional marketing authorization. Last September, Intercept and Alfasigma announced the voluntary withdrawal of Ocaliva from the U.S. market.
When Ocaliva first reached PBC patients a decade ago, the daily pill was the only second-line PBC treatment. The landscape changed with the 2024 accelerated FDA approvals of two PBC drugs: Iqirvo, from Ipsen and Genfit, and Livdelzi, from Gilead Sciences. Both drugs are small molecules designed to target and activate PPAR, receptors in the liver that regulate metabolic processes. Alfasigma can compete by providing patients with a drug offering a different mechanism of action.
GSK’s FDA submission for linerixibat is based on Phase 3 data showing the IBAT inhibitor led to rapid and sustained improvement on itching compared to a placebo. The FDA is expected to render a regulatory decision for the drug by March 24. Applications for linerixibat are also under review in the European Union, United Kingdom, China, and Canada.
“With our deep hepatology expertise and strong global footprint, we are uniquely positioned to lead the worldwide commercialization of linerixibat,” Alfasigma CEO Francesco Balestrieri said in a prepared statement. “This agreement underscores our strategic focus on bringing meaningful new treatments to patients and improving outcomes for communities around the world.”
Privately held Alfasigma reported €1.87 billion (about $2.17 billion) in revenue for 2024, a 37% increase compared to the prior year. The company says its rare disease portfolio focuses on therapies for gastrointestinal disorders and hepatology. Meanwhile, GSK said it can now sharpen focus on its drugs in development for prevalent liver disorders, including chronic hepatitis B, MASH, and alcohol-related liver disease (ALD).
Beyond Alfasigma’s upfront payment to GSK, the agreement makes the British pharmaceutical company eligible for an additional $100 million upon FDA approval of linerixibat. The deal also calls for Alfasigma to pay $20 million upon European Union and United Kingdom approval; up to $270 million more is tied to sales-based milestone payments. GSK will also receive royalties on Alfasigma’s sales of the drug.
Photo: Niccolo Biddau/Alfasigma
