‘Sustained improvement’ in markers of liver injury, pruritis with seladelpar in PBC
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Key takeaways:
- More than 70% of patients with primary biliary cholangitis achieved the primary study endpoint with 10 mg seladelpar daily.
- Alkaline phosphatase normalization occurred in 37.2% of patients.
WASHINGTON — Seladelpar use led to “rapid, marked and sustained improvement” in markers of cholestasis and liver injury among patients with primary biliary cholangitis, according to interim results of the ongoing, phase 3 ASSURE study.
“The study was initiated because there is currently a major unmet need for patients with primary biliary cholangitis (PBC) and insufficient response to the first-line therapy, ursodeoxycholic acid,” Cynthia Levy, MD, professor of medicine at University of Miami Miller School of Medicine, told Healio. “These patients are at risk for progression to cirrhosis and end-stage liver disease.”
She continued, “Furthermore, ursodeoxycholic acid does not improve patients’ symptoms, and pruritus in particular can have a major negative impact on their quality of life.”
Levy and colleagues evaluated interim safety and efficacy results from 174 patients (mean age, 58.6 years; 94% women) with PBC who previously had participated in seladelpar trials and also experienced inadequate response or intolerance to ursodeoxycholic acid. All patients received open-label, oral seladelpar 10 mg daily.
The primary study endpoints included a composite response of alkaline phosphatase (ALP) less than 1.67 times the upper limit of normal, a reduction in ALP of at least 15% and total bilirubin less than or equal to the upper limit of normal, as well as change from baseline through month 12 in ALP, gamma-glutamyl transferase (GGT), alanine transaminase and total bilirubin.
At baseline, mean ALP was 270.5 U/L and total bilirubin was 0.75 mg/dL (13.8% > upper limit of normal). Most patients (96.6%) also were being treated with ursodeoxycholic acid and 19% had cirrhosis.
As of June 29, 2023, 85% of patients reached 12 months of treatment and 70.3% achieved the composite response endpoint. ALP normalization occurred among 37.2%, with a mean percent change of –44.4% (–144.4 U/L) from baseline. Seladelpar also lowered GGT, ALT and total bilirubin among 36.4%, 25.2% and 9.2%, respectively.
“Seladelpar use led to a rapid, marked and sustained improvement in alkaline phosphatase and other markers of liver injury, corroborating results of the phase 3 trial,” Levy said. “Seladelpar led to sustained improvement in itching for that subpopulation of patients with moderate to severe pruritus at entry.”
In addition, “seladelpar was safe and well-tolerated,” she noted. No treatment-related serious adverse events were reported, although 4% of patients discontinued due to adverse events.
“Seladelpar is an investigational product, not yet approved for use in clinical practice,” Levy told Healio. “However, we look forward to the availability of such a medication that can improve both the long-term outcomes of PBC, as suggested by biochemical improvement, and the quality of life of our patients.”
She added: “Among other things, continued research is needed to better understand the long-term efficacy and safety of seladelpar in specific subpopulations, such as those with advanced liver disease and those who failed second line therapies.”
In a subsequent interview, Tim Watkins, MD, vice president at Gilead Sciences told Healio: “This interim data demonstrates that seladelpar, an investigational PPAR-delta agonist, shows a durable biochemical response, an increased proportion of people achieving ALP normalization and reductions in pruritus in patients living with PBC.”
He continued: “These data further support the efficacy and safety profile of seladelpar observed across its robust development program, including the pivotal RESPONSE study, and continue to indicate that seladelpar has the potential to be an important new therapy that could help transform treatment for people living with PBC, if approved.”
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Levy C, et al. Efficacy and safety of seladelpar in patients with primary biliary cholangitis in the ASSURE study: Interim results. Presented at: Digestive Disease Week; May 18-21, 2024; Washington (hybrid).
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