Gilead, Ipsen Highlight Phase III PBC Data Ahead of PDUFA Dates

Gilead Sciences unveiled promising results for its drug candidate seladelpar in a recent Phase III trial aimed at treating primary biliary cholangitis (PBC), a rare liver condition. Despite these advancements, the company faces stiff competition from Ipsen Biopharmaceuticals, which may secure market approval in the United States sooner.

The Phase III ASSURE trial demonstrated that seladelpar, a peroxisome proliferator-activated receptor delta (PPAR) agonist, delivers "rapid and sustained" benefits for PBC patients. Key findings include significant normalization of liver biomarkers and a notable reduction in pruritus or itching. According to the trial data, 70% of patients achieved the composite response endpoint, which involves maintaining alkaline phosphatase (ALP) levels below 1.67 times the upper limit of normal (ULN), a decrease in ALP levels of at least 15%, and total bilirubin levels at or below the ULN.

Further, 42% of patients reached ALP normalization at the 24-month mark, an important indicator of liver disease progression. Patients also experienced sustained relief from itching, with mean reductions of 3.8 and 3.1 points on the numerical rating scale at 12 and 24 months, respectively. These results suggest that seladelpar could set a new benchmark in PBC treatment, according to Palak Trivedi, a consultant hepatologist at the University of Birmingham.

Gilead acquired seladelpar through its $4.3 billion acquisition of CymaBay Therapeutics earlier this year. The company expects an FDA decision on this drug by August 14, 2024. However, Ipsen Biopharmaceuticals is hot on their heels with its candidate elafibranor, which also aims to treat PBC and has shown promising results in long-term trials.

Ipsen's elafibranor, another PPAR agonist, reported encouraging outcomes in its Phase III ELATIVE trial. Scheduled for a U.S. Food and Drug Administration (FDA) review by June 10, 2024, elafibranor showed significant improvements at week 52, including "greater reductions" in the 5-D itch score and meaningful reductions in the itch domain of PBC-40 when compared to a placebo. Additionally, patients reported an enhanced quality of life, marked by reduced severity of itching, fewer sleep disturbances, and less emotional impact from itching. By the 52-week mark, 58% of patients treated with elafibranor reported itch relief, compared to 27% in the placebo group, and 80% experienced no sleep disturbances.

Sandra Silvestri, executive vice president and chief medical officer at Ipsen, highlighted that these long-term data from the ELATIVE study underscore elafibranor’s potential as an effective treatment option for PBC patients.

Ipsen secured the rights to elafibranor through a strategic partnership with Genfit in 2021. The deal involved an upfront payment of €120 million ($130.5 million) and could total up to €360 million ($391.7 million) in milestones.

Both Gilead Sciences and Ipsen Biopharmaceuticals are making significant strides in the race to provide new, effective treatments for primary biliary cholangitis. While Gilead’s seladelpar shows strong potential, it remains to be seen whether it can outpace Ipsen’s elafibranor in securing FDA approval and reaching the market first.