PBC Drug Livdelzi From Gilead Gets Speedy Approval

Gilead Sciences' Livdelzi (seladelpar) has been granted accelerated approval by the FDA for the treatment of primary biliary cholangitis (PBC). This decision is supported by findings from the Phase III RESPONSE trial (NCT04620733), which showed that Livdelzi is the first medication to achieve notable reductions in alkaline phosphatase (ALP) normalization and alleviate pruritus—key indicators of PBC progression.

At the 12-month mark, 25% of patients treated with Livdelzi saw their ALP levels normalize, while no patients on placebo experienced this outcome. Additionally, Livdelzi significantly reduced pruritus scores at six months compared to the placebo group. By the end of 12 months, 62% of those receiving Livdelzi achieved a composite biochemical response, compared to only 20% of placebo patients.

With this approval, Livdelzi enters a competitive market alongside established therapies such as Ocaliva (obeticholic acid) and ursodeoxycholic acid. Ocaliva, developed by Intercept Pharmaceuticals and acquired by Alfasigma in late 2023, is a key competitor. Gilead Sciences obtained seladelpar, a peroxisomal proliferator-activated receptor delta agonist, in March 2024 through its $4.3 billion acquisition of CymaBay Therapeutics.

In a discussion with Pharmaceutical Technology, CymaBay's CEO Sujal Shah highlighted Livdelzi's edge over Ocaliva by noting that Livdelzi helps alleviate itching, whereas Ocaliva tends to worsen it. Shah emphasized that Livdelzi offers a competitive benefit in this regard. Furthermore, he pointed out that while ursodeoxycholic acid frequently fails to provide sufficient relief, leading to ongoing liver damage, Livdelzi has demonstrated its ability to elicit positive responses in these challenging cases.

GlobalData forecasts that Livdelzi will reach $558 million in revenue by 2030. Before Alfasigma acquired it, Ocaliva generated $285.7 million in revenue for FY 2022 and $83.7 million in Q2 2023, according to the company's financial reports. Primary biliary cholangitis (PBC) is a rare autoimmune disorder that causes inflammation and damage to the liver's bile ducts, impacting around 130,000 Americans. As PBC advances, it raises the risk of liver-related mortality, and currently, there is no definitive cure for the condition.

The continuation of FDA approval hinges on proving significant clinical benefits. Gilead is running two Phase III trials: ASSURE (NCT03301506), an open-label study assessing Livdelzi’s safety and tolerability, and AFFIRM (NCT06051617), a double-blind trial examining Livdelzi’s clinical effects in patients with PBC and compensated cirrhosis. Following the FDA announcement, Gilead’s share price closed nearly 1% higher than its opening value, according to Yahoo Finance. The company’s current market capitalization stands at $92 billion. GlobalData, the parent organization of Pharmaceutical Technology, provides these insights.