Seladelpar achieves high statistical significance for the primary and key secondary endpoints in the phase III RESPONSE trial in primary biliary cholangitis

The study evaluated the safety and efficacy of seladelpar, a potent, selective, orally active delpar agonist, in development for the treatment of adult patients with primary biliary cholangitis (PBC). The registration trial achieved the primary and all key secondary endpoints and supports advancement to regulatory discussions and filing for regulatory approval with the FDA, the Medicines and Healthcare products Regulatory Agency (MHRA), and the European Medicines Agency (EMA).

A total of 61.7% of patients on seladelpar 10 mg (n=128) met the primary composite endpoint related to serum alkaline phosphatase and bilirubin at 12 months versus 20.0% on placebo (n=65; p<0.0001). the anti-cholestatic effect of seladelpar was supported by the normalization of alkaline phosphatase at 12 months (key secondary endpoint) in 25.0% of patients on seladelpar vs. zero on placebo (p><0.0001). the least-squares mean percent reduction in alkaline phosphatase at 12 months was 42.4% in the seladelpar group vs. 4.3% in the placebo group.

Seladelpar treatment compared to placebo also demonstrated a statistically significant reduction in pruritus, or itch, (key secondary endpoint) after 6 months of treatment. Seladelpar-treated patients with a baseline Numerical Rating Scale (NRS) greater than 4 (moderate to severe pruritus) had a least-square mean reduction of 3.2 points in pruritus NRS (n=49) compared to 1.7 points for patients in the placebo group (n=23; p<0.005).

Overall, safety was comparable between placebo and seladelpar groups and was consistent with previous studies. Treatment-emergent adverse events, serious adverse events, and patient discontinuations were generally balanced across the treatment and placebo arms. There were no treatment-related serious adverse events in the study. Seladelpar's tolerability profile appeared favorable and consistent with previous studies.

"The topline results seen in the RESPONSE trial are exciting for highlighting the potential for an efficacious and safe new therapy that not only achieves the composite improvements in liver tests, but for a significant proportion of patients, normalizes these measures. Further, the results support that seladelpar reduced itch, a particularly challenging symptom that continues to negatively impact quality of life for many PBC patients," said Gideon Hirschfield, M.D., Lily and Terry Horner Chair in Autoimmune Liver Disease Research, Toronto Centre for Liver Disease. "While existing first and second-line therapies have helped patients living with PBC, this is the first potential therapy to show promise in both significantly improving markers associated with risk of disease progression while also significantly reducing itch."

"The results from RESPONSE support our conviction that seladelpar has the potential to advance patient care by improving measures of disease activity and reducing symptom burden. They are consistent with previous findings in what we believe has been an exceptionally robust development program in PBC. We believe that the delpar mechanism is unique with its ability to normalize markers of cholestasis coupled with reductions in pruritus," said Sujal Shah, President and CEO of CymaBay. "Many patients with PBC suffer from incessant itching while knowing that their disease can progress to the point where a liver transplant could become their only option. These results represent an important step toward potentially changing the treatment paradigm for patients living with PBC. We deeply appreciate the participation of patients across all of our studies in PBC and the support we have received from investigators, their teams and our many partners involved in advancing the development of seladelpar through this significant milestone."