FDA OKs linerixibat, now Lynavoy, as first US treatment for itch in PBC
Advocate says approval 'offers hope' for those with intense itching
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Lynavoy (linerixibat) is now approved in the U.S. as an oral treatment for cholestatic pruritus, or intense itch due to problems in how the digestive fluid bile flows in the body, in adults with primary biliary cholangitis (PBC).
The decision from the U.S. Food and Drug Administration (FDA) makes Lynavoy the first therapy to be approved in the country for PBC-related itch, which can profoundly affect the quality of life of this patient population, according to a company press release from GSK, the therapy’s developer.
The medication is under regulatory review in Canada, the European Union, the U.K., and China, where it was given priority review.
“The approval of Lynavoy in the US gives patients a much needed treatment option that offers rapid, significant and sustained improvement in the debilitating effects of itch caused by PBC,” said Kaivan Khavandi, senior vice-president and global head of respiratory, immunology & inflammation R&D and translational & development sciences at GSK. “For many patients, cholestatic pruritus remains a persistent, poorly addressed condition.”
GSK recently entered a licensing agreement with Alfasigma, which will acquire the exclusive rights to further develop, produce, and market Lynavoy worldwide.
The FDA decision was welcome news in the PBC community.
“Cholestatic pruritus has been underestimated and overlooked for far too long, despite its significant impact on people living with PBC,” said Carol Roberts, president of The PBCers Organization, an online and in-person support group for those affected by the condition.
“Seeing a treatment specifically developed for chronic itch finally reach patients is a significant step forward and offers hope for those in need,” Roberts said.
Pruritus, or itch, affects nearly 90% of PBC patients
PBC is a chronic form of cholangitis, or inflammation of the tubes that carry bile from the liver, where it is produced, to the intestines, where it helps digest food. As a result, bile does not flow well and can accumulate in the liver, causing damage to the organ.
When present in excess in the liver, bile can also enter the bloodstream, causing pruritus and other symptoms. Pruritus is reported in as many as 89% of people with PBC, and can affect sleep and overall quality of life.
Lynavoy is an oral therapy designed to block the ileal bile acid transporter (IBAT), a protein that normally helps recycle bile by moving it from the intestines back to the liver. By suppressing IBAT, the therapy, taken as oral tablets twice a day, is expected to increase bile excretion in feces, thereby reducing its accumulation in the liver, preventing it from entering circulation, and easing associated symptoms.
The medication received orphan drug designation in the U.S., the EU, and Japan for cholestatic pruritus in people with PBC. These statuses are meant to accelerate its clinical development and regulatory review.
Its approval was based mainly on data from GLISTEN (NCT04950127), a global Phase 3 clinical trial that tested linerixibat against a placebo. In the study, 238 adults with a diagnosis of PBC and moderate to severe pruritus were randomly assigned to receive either Lynavoy, at a dose of 40 mg, or a placebo, twice daily for 24 weeks, or nearly six months.
Lynavoy bested a placebo in trial at reducing itch
The study met its main goal of showing that Lynavoy was significantly more effective than a placebo at reducing pruritus, as assessed with a rating scale for worst monthly itch. Significant differences between the two groups were observed as early as two weeks, meeting one of the study’s secondary goals.
A clinically meaningful reduction of at least three points in itch scores, indicating less itch, was achieved more often in participants treated with Lynavoy (56% vs. 43%).
Those on Lynavoy also had significantly lower monthly sleep interference scores, indicating less impact of itch on sleep, over 24 weeks, meeting another of the study’s secondary goals.
The impact of itch on people living with PBC can be profound. … The FDA’s decision marks a major milestone in PBC pruritus care that addresses a critical area of unmet need.
After completing the placebo-controlled part of the study, participants either continued on Lynavoy or the placebo, or switched to the other for eight weeks, or about two months. Those who switched to Lynavoy had a reduction in itch scores within two weeks, consistent with findings of the first part of the study. In contrast, those who switched to the placebo experienced an increase in their itch scores.
Linerixibat was generally safe and well tolerated, with the most common side effect being diarrhea.
“The impact of itch on people living with PBC can be profound and treatment options have until now been limited,” said Christopher Bowlus, MD, the Lena Valente professor and chief of gastroenterology and hepatology at University of California Davis.
According to Bowlus, “the FDA’s decision marks a major milestone in PBC pruritus care that addresses a critical area of unmet need.”
