Seladelpar normalizes ALP, reduces pruritis vs. placebo in primary biliary cholangitis
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Key takeaways:
- A greater percentage of patients treated with seladelpar achieved biochemical response and normalization of alkaline phosphatase vs. placebo.
- Seladelpar also significantly reduced pruritis.
A “significantly greater” percentage of patients with primary biliary cholangitis achieved biochemical response, alkaline phosphatase normalization and reduction in pruritis when treated with seladelpar vs. placebo, according to a study.
“Many people living with PBC do not experience a normalization of ALP or meaningful symptom relief with currently available treatments,” Gideon M. Hirschfield, PhD, Lily and Terry Horner Chair in Autoimmune Liver Disease at the University of Toronto, said in a related press release. “Pruritus or severe itch significantly impairs the quality of life of our patients, and current second-line treatment frequently worsens itch. New options, that are potent, effective and safe, are needed for people living with this chronic debilitating autoimmune condition.”
In the multicenter, double-blind, placebo-controlled, phase 3 RESPONSE trial, Hirschfield and colleagues evaluated the safety and efficacy of seladelpar among 193 adult patients with primary biliary cholangitis, who had an inadequate response or unacceptable side effects with ursodeoxycholic acid. Patients were randomized to receive oral, once-daily seladelpar 10 mg (n = 128) or matching placebo (n = 65) for up to 12 months.
The primary studied outcome was biochemical response, defined as an alkaline phosphatase (ALP) level less than 1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and a normal total bilirubin level at month 12. Key secondary endpoints included ALP normalization and change from baseline in weekly mean pruritus score at month 6.
Researchers noted 93.8% of patients received ursodeoxycholic acid as standard-of-care background therapy and 90.2% completed the trial.
According to study results published in The New England Journal of Medicine, a greater percentage of patients in the treatment group met the primary endpoint, achieving biochemical response (61.7% vs. 20%; difference = 41.7 percentage points; 95% CI, 27.7-53.4) and normalization of ALP (25% vs. 0%; difference = 25 percentage points; 95% CI, 18.3-33.2). The least-squares mean ALP level decreased by 42.4% vs. 4.3%, respectively, a difference of –38.2 percentage points (95% CI, –46.3 to –30.1). Total bilirubin remained stable in both groups through 12 months.
Further, among the 49 patients who reported moderate to severe pruritis at baseline (38.3% on seladelpar; 35.4% on placebo), there was a “significantly greater” reduction in pruritis score at 6 months in the seladelpar group (change from baseline = –3.2 vs. –1.7 points; least-squares mean difference [LSM] = –1.5 points; 95% CI, –2.5 to –0.5). The change in pruritis score also favored seladelpar in the overall study population (–1.3 vs. –0.4 points; LSM = –0.9 points; 95% CI, –1.4 to –0.5).
The incidence of adverse events was similar between groups, with 86.7% of patients on seladelpar experiencing adverse events compared with 84.6% on placebo. Serious adverse events were reported in 7% and 6.2%, respectively.
“The data, together with the existing substantial experience gained from prior studies, robustly support the potential for seladelpar to raise the bar in PBC treatment,” Hirschfield said in the release. “In this rigorous international trial, people living with PBC saw substantial rates of normalization of serum liver tests and clear statistically significant improvement in itch. Benefits were also noted in those people living with compensated cirrhosis.”
Reference:
- The New England Journal of Medicine publishes positive phase 3 RESPONSE data of CymaBay's seladelpar in primary biliary cholangitis. https://www.cymabay.com/investors-media/news-events/press-releases/detail/594/the-new-england-journal-of-medicine-publishes-positive. Published Feb. 21, 2024. Accessed Feb. 27, 2024.
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