Gilead Sciences’ Livdelzi (seladelpar) has received an accelerated approval from the US Food and Drug Administration (FDA) to treat primary biliary cholangitis (PBC).
The approval is based on results from the Phase III RESPONSE trial (NCT04620733), which demonstrated Livdelzi to be the first treatment yielding significant reductions in alkaline phosphatase (ALP) normalisation and pruritus—significant markers of PBC progression.
ALP levels normalised at 12 months for 25% of Livdelzi-treated patients compared to none on placebo. Change in pruritus score at six months was significantly reduced among Livdelzi-treated patients compared to those taking placebo. Overall, 62% of patients on Livdelzi achieved composite biochemical response at 12 months, achieved by just 20% of placebo patients.
With this regulatory nod, Livdelzi enters a space dominated by other approved therapies like Ocaliva (obeticholic acid) and ursodeoxycholic acid. Ocaliva was developed by Intercept Pharmaceuticals, which was acquired by Alfasigma in late 2023. Gilead gained the rights to seladelpar, a peroxisomal proliferator-activated receptor delta agonist, in March 2024 as part of its acquisition of CymaBay Therapeutics for $4.3b.
In an interview with Pharmaceutical Technology, Cymabay CEO Sujal Shah said Livdelzi can reduce itching, compared to Ocaliva which increases it, giving Livdelzi a competitive advantage. Ursodeoxycholic acid often results in inadequate responses leading to continued liver damage, and Livdelzi has been shown to induce responses in these patients.
GlobalData projects Livdelzi revenues to touch $558m by 2030. Prior to it being acquired by Alfasigma, Ocaliva earned 285.7m in FY 2022, and $83.7m in 2Q23, as per the company’s financials.
PBC is a rare autoimmune disease involving inflammation and destruction of bile ducts in the liver, which affects approximately 130,000 Americans. Progression of PBC increases the risk of liver mortality and there is no curative therapy available.
Continued FDA approval will depend on verification of substantial clinical benefit. Gilead is currently conducting the Phase III trials ASSURE (NCT03301506), an open-label trial investigating the safety and tolerability of Livdelzi, and AFFIRM (NCT06051617), a double-blind trial exploring clinical outcomes of Livdelzi in patients with PBC and compensated cirrhosis.
On the day of the FDA announcement, the market closed with Gilead share prices almost 1% higher than they were when the market opened, as per Yahoo finance. The company’s market cap is currently $92bn.
GlobalData is the parent company of Pharmaceutical Technology.
Following the approval, Carol Robers, President of the nonprofit PBCers Organisation, stated, “Those living with PBC share common symptoms, including incessant itching or skin-crawling sensations, as well as debilitating fatigue that is made worse by the itching at night – The availability of a new treatment option that can help reduce this intense itching while also improving biomarkers of active liver disease is a milestone for our community.”
