Seladelpar (1) – Seladelpar Gilead®, Seladelpar Gilead®

• Clinical trials
  • The RESPONSE trial is a multicentre, randomised, double-blind, placebo-controlled Phase III trial which investigated the efficacy, safety and tolerability of seladelpar in patients with PBC who had an inadequate response to or were intolerant of UDCA.

Adults with primary biliary cholangitis (PBC) who have shown an inadequate response to or are intolerant of ursodeoxycholic acid (UDCA)

• In summary, the additional benefit of seladelpar is assessed as follows: For adults with primary biliary cholangitis (PBC) who have shown an inadequate response to or intolerance of ursodeoxycholic acid (UDCA), there is an indication for a minor additional benefit for Seladelpar.
• Taking the available results as a whole, an indication of a minor additional benefit of Seladelpar is identified based on the demonstrated advantage at the endpoint of pruritus.
• mortality
  • Deaths from any cause were recorded as part of the safety assessment. No deaths occurred in the study. There is therefore no statistically significant difference between the study arms.
• Morbidity – Clinical events
  • The clinical PBC events defined as endpoints were liver transplantation, a MELD score ≥ 15 (Model for End-Stage Liver Disease) at at least two consecutive visits, ascites requiring treatment, hospitalisations due to variceal haemorrhage, hepatic encephalopathy or spontaneous bacterial peritonitis, and deaths.
  • Hospitalisations occurred in both the intervention and control arms. However, no statistically significant difference was observed between the study arms. With regard to the other endpoints, no events occurred in either treatment arm.
• Morbidity – pruritus
  • The endpoint of pruritus is a patient-relevant endpoint within the therapeutic indication.
  • A statistically significant advantage of seladelpar over placebo was observed in both the pruritus NRS and the total score, as well as in all individual domains of the 5-D Itch Scale. Furthermore, based on the respective Hedges’ g values, it can be inferred from the statistically significant results for the pruritus NRS, the total score of the 5-D Itch Scale and the ‘impairment’ domain of the 5-D Itch Scale that the effect is clinically relevant.
• quality of life
  • For the PBC-40 endpoint, there was no statistically significant difference between the treatment arms.
• Side effects
  • The safety results for the overall population of the RESPONSE study show no statistically significant differences between the treatment arms, neither in terms of serious adverse events (SAEs) nor severe adverse events (CTCAE grade 3 or 4), nor in therapy discontinuations due to AEs.
• Overall assessment
  • Results from the RESPONSE study are available for the benefit assessment of seladelpar in the treatment of adults with primary biliary cholangitis (PBC) who have shown an inadequate response to or intolerance of ursodeoxycholic acid (UDCA), results are available from the RESPONSE study, in which seladelpar was compared with placebo over a period of 12 months.
  • No deaths occurred in the RESPONSE study.
  • In the morbidity endpoint category, the patient-relevant endpoints of clinical events and pruritus were assessed. For the endpoint of pruritus, Seladelpar demonstrated a statistically significant advantage over placebo in both the Pruritus-NRS measurement tool and in the total score and all individual domains of the 5-D Itch Scale. No clinical events such as liver transplants, a MELD score ≥ 15 or ascites requiring treatment occurred. For the endpoint ‘hospitalisation’, there was no statistically significant difference between the treatment arms.
  • In the quality of life endpoint category, there was no statistically significant difference between the treatment arms for the PBC-40 endpoint.
  • In the ‘side effects’ endpoint category, no statistically significant difference was observed between the treatment arms.
  • Taking the available results as a whole, a minor additional benefit of seladelpar is observed, based on the demonstrated advantage in the ‘pruritus’ endpoint.

Courtesy translation only, please refer to the German original.