Elafibranor (1) – Iqirvo®

• Clinical trials
  • The ELATIVE trial is a multicentre, randomised, double-blind, placebo-controlled Phase III trial which investigated the efficacy, safety and tolerability of elafibranor 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)

• For adults with primary biliary cholangitis (PBC) who have shown an inadequate response to or are intolerant of ursodeoxycholic acid (UDCA), there is a hint of a minor additional benefit for elafibranor.
• In the overall review of the available results, a hint of a minor additional benefit of elafibranor is identified on the basis of the demonstrated improvement in health-related quality of life.
• Overall, given the uncertainties mentioned regarding the validity of the evidence, there is a hint of an additional benefit.
• mortality
  • Deaths from any cause were recorded as part of the safety monitoring. Two deaths occurred in the elafibranor group during the study. No statistically significant difference was observed between the study arms.
  • Two deaths occurred in the elafibranor arm of the study.
• morbidity
  • The composite endpoint of clinical events comprises the sub-components of liver transplantation, uncontrolled ascites requiring treatment, and hospitalisations due to variceal haemorrhage, hepatic encephalopathy or spontaneous bacterial peritonitis.
  • During the study, one person in the elafibranor arm and no one in the control arm developed uncontrolled ascites requiring treatment. However, no statistically significant difference was observed between the study arms.
  • No events occurred in either treatment arm with regard to the other sub-components.
• Morbidity – pruritus
  • The endpoint of pruritus represents a patient-relevant endpoint within the therapeutic indication.
  • Itch symptoms were assessed in the study using two instruments: the ‘PBC Worst Itch NRS’ and the ‘5-D Itch Scale’ (5-D Itch).
  • Based on the responder analyses, a statistically significant advantage of elafibranor over placebo was observed for the 5-D Itch in the ‘severity’ and ‘direction’ domains. However, these advantages were not reflected in either the overall score of the 5-D Itch or in the domains ‘Duration’, ‘Distribution’ and ‘Impairment’.
  • Based on the responder analyses using the PBC Worst Itch NRS, no statistically significant differences were observed between the treatment arms.
  • Although a statistically significant advantage was observed for the endpoint ‘itching’ in the ‘severity’ and ‘direction’ domains of the 5-D Itch, this was not reflected in either the total score of the 5-D Itch or in the other domains. Similarly, the PBC Worst Itch NRS showed no statistically significant differences between the treatment arms for the endpoint of itch.
• Morbidity – Health Status
  • Patients’ health status is considered to be of relevance to them. In the study, it was assessed using the visual analogue scale of the European Quality of Life 5-Dimension 5-Level Questionnaire (EQ-5D-5L-VAS).
  • In the responder analysis, no statistically significant difference was observed between the treatment arms for the EQ-5D-5L-VAS endpoint.
• Morbidity – daytime sleepiness
  • The endpoint of daytime sleepiness is considered patient-relevant in this therapeutic indication, particularly in the context of nocturnal itching. In the study, daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS).
  • In the responder analysis, no statistically significant difference was observed between the treatment arms for the ESS endpoint.
• Morbidity – Fatigue
  • The endpoint ‘fatigue’ represents a patient-relevant endpoint in this therapeutic indication and was assessed in the study using the PROMIS Fatigue Short Form 7a.
  • In the responder analysis, no statistically significant difference was observed between the treatment arms for the PROMIS Fatigue Short Form 7a endpoint.
• quality of life
  • The PBC-40 questionnaire, comprising the domains of general symptoms (7 items), pruritus (3 items), fatigue (11 items), cognitive functioning (6 items), the social domain and the emotional domain, was used to assess quality of life.
  • In the responder analysis, a statistically significant advantage of elafibranor over placebo was observed in the ‘itching’ domain of the PBC-40 questionnaire. In the other domains of the PBC-40 questionnaire (‘general symptoms’, ‘fatigue’, ‘cognitive functioning’, ‘emotional functioning’ and ‘social functioning’), no statistically significant differences were observed between the treatment arms.
• Side effects
  • The safety results for the overall population of the ELATIVE study showed no statistically significant differences between the treatment groups in terms of serious adverse events (SAEs), severe adverse reactions (SARs) or therapy discontinuations due to AEs.
  • No statistically significant differences were observed between the treatment arms in the category of side effects.
• Overall assessment
  • Results from the ELATIVE study are available for the benefit assessment of elafibranor 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 ELATIVE study, in which elafibranor was compared with placebo over a period of 52 weeks.
  • In the morbidity endpoint category, the endpoints of clinical events, pruritus, health status, daytime sleepiness and fatigue were assessed. For the endpoint of pruritus, statistically significant advantages were observed in the ‘severity’ and ‘direction’ domains of the 5-D Itch scale. However, these advantages were not reflected in the overall 5-D Itch score or in the other domains. Similarly, based on the PBC Worst Itch NRS, no statistically significant differences were observed between the treatment arms for the itch endpoint. No statistically significant differences were observed between the treatment arms for the other endpoints in the morbidity category either.
  • In the quality of life endpoint category, a statistically significant advantage of elafibranor was observed in the ‘itching’ domain of the PBC-40 questionnaire. No statistically significant differences were observed between the treatment arms in the other domains.
  • In the ‘side effects’ endpoint category, no statistically significant differences were observed between the treatment arms.
  • Taking the available results as a whole, a minor additional benefit of elafibranor is identified on the basis of the demonstrated advantage in health-related quality of life.

Courtesy translation only, please refer to the German original.