Gilead's Livdelzi for PBC wins accelerated approval

Livdelzi (seladelpar), developed by Gilead Sciences, has recently garnered accelerated approval from the US Food and Drug Administration (FDA) for the treatment of primary biliary cholangitis (PBC). This approval comes on the heels of promising results from the Phase III RESPONSE trial (NCT04620733), which highlighted Livdelzi as a groundbreaking treatment option capable of significantly reducing alkaline phosphatase (ALP) normalisation and pruritus—crucial markers in the progression of PBC.

The RESPONSE trial findings indicated that 25% of patients receiving Livdelzi experienced normalised ALP levels at the 12-month mark, a substantial difference compared to the placebo group, which showed no such improvement. Additionally, the trial reported a significant reduction in pruritus scores at six months among those treated with Livdelzi, in contrast to the placebo group. Overall, 62% of Livdelzi-treated patients achieved a composite biochemical response at 12 months, compared to just 20% of placebo recipients.

With its recent FDA approval, Livdelzi makes a notable entry into a market that already includes treatments such as Ocaliva (obeticholic acid) and ursodeoxycholic acid. Ocaliva, originally developed by Intercept Pharmaceuticals and later acquired by Alfasigma in 2023, has been a prominent therapy in this space. Gilead acquired the rights to seladelpar in March 2024 through its $4.3 billion acquisition of CymaBay Therapeutics.

In an interview, CymaBay CEO Sujal Shah remarked on Livdelzi's ability to reduce itching, a common symptom among PBC patients, unlike Ocaliva, which has been known to exacerbate it. This gives Livdelzi a competitive edge, especially given that ursodeoxycholic acid often fails to elicit adequate responses, leading to ongoing liver damage. Livdelzi has demonstrated effectiveness in patients who do not respond adequately to existing therapies.

Primary biliary cholangitis is a rare autoimmune disease marked by chronic inflammation and the gradual destruction of bile ducts in the liver. It affects about 130,000 Americans and significantly increases the risk of liver mortality over time, with no current cure available.

The FDA has stated that continued approval for Livdelzi will depend on further verification of its clinical benefits. To this end, Gilead is conducting additional Phase III trials, namely ASSURE (NCT03301506) and AFFIRM (NCT06051617), to investigate the safety, tolerability, and clinical outcomes of Livdelzi in patients with PBC and compensated cirrhosis.

On the day of the FDA's announcement, Gilead's share prices saw a nearly 1% increase by market close, raising the company's market cap to $92 billion. This surge reflects investor confidence in Livdelzi's market potential and Gilead's broader strategic direction.

Following the approval, Carol Robers, President of the PBCers Organisation, expressed optimism about the new treatment option. She highlighted that many PBC patients endure relentless itching and debilitating fatigue, symptoms that are often exacerbated during nighttime. The introduction of a treatment that can alleviate this intense itching while also improving key biomarkers of liver health represents a significant milestone for the PBC community.

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