Genuinely exciting phase 3 results for CymaBay’s seladelpar
CymaBay Therapeutics, Inc., a biopharmaceutical company focusing on innovative therapies for liver and chronic diseases, recently (Feb 21) announced the publication of detailed results from the RESPONSE phase 3 trial in The New England Journal of Medicine (NEJM).
The trial evaluated seladelpar, an investigational agent and the only potent, selective peroxisome proliferator-activated receptor delta (PPARδ) agonist, in adults with primary biliary cholangitis (PBC).
PBC is a rare, chronic inflammatory liver disease primarily affecting women. It is characterized by impaired bile flow, leading to liver inflammation and destruction, with symptoms including pruritus and fatigue. Progression of PBC can lead to increased risks of liver-related mortality.
The findings revealed rapid and sustained improvements in reducing cholestasis and liver injury, along with significant reductions in pruritus (itching) across multiple measures. These results bring hope for patients suffering from this chronic liver disease.
RESPONSE, a global study lasting one year, involved 193 individuals with PBC who were randomized in a 2:1 ratio to receive seladelpar 10mg or placebo once daily. The trial aimed to address the inadequacy or intolerance to current standard treatment, ursodeoxycholic acid (UDCA). The primary endpoint, a composite of ALP and total bilirubin at month 12, was achieved by 61.7% of patients treated with seladelpar compared to 20.0% with placebo.
Dr Gideon Hirschfield is Lily and Terry Horner Chair in autoimmune liver disease research at the Toronto Centre for Liver Disease.
He said: “The RESPONSE data are genuinely exciting. It supports the potential for seladelpar to raise the bar in PBC treatment.
“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.”
Secondary endpoints also favored seladelpar, with 25.0% achieving ALP normalization compared to none in the placebo group. Additionally, significant reductions in ALT and GGT levels were observed in patients receiving seladelpar.
Improvement in pruritus was evident as early as week 4 and was sustained through to month 12, with seladelpar patients reporting greater decreases compared to placebo across multiple assessment scales.
Regarding safety, adverse events were similar between seladelpar and placebo groups, with COVID-19 and pruritus being the most common. Serious adverse events were reported at low rates and were not considered associated with seladelpar treatment.
“The publication of the pivotal phase 3 data for seladelpar in The New England Journal of Medicine recognizes the importance of these findings, the potential of this investigational agent to help people living with PBC, and the significant need for innovation in this area,” said Charles McWherter, chief scientific officer and president of research and development at CymaBay.
“We are thrilled that these results are now available to benefit researchers, patients, and the broader medical community in our collective pursuit of PBC treatment transformation.”
With a New Drug Application (NDA) accepted for priority review by the FDA in February 2024 and plans for marketing authorization applications in Europe, seladelpar holds promise as a breakthrough therapy for PBC patients in need of effective alternatives to current treatments.
Seladelpar is an investigational treatment for PBC, showing potential as a first-in-class oral, selective PPARδ agonist. It targets critical metabolic and liver disease pathways with high unmet medical needs, offering hope for improved outcomes in PBC treatment.
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