Ipsen receives CHMP positive opinions for Iqirvo (elafibranor) in primary biliary cholangitis and Kayfanda (odevixibat) in Alagille syndrome, two rare cholestatic liver diseases.

Iqirvo (elafibranor) has been recommended for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA or as a monotherapy in patients unable to tolerate UDCA.

Kayfanda (odevixibat) has also received a positive opinion from CHMP as a treatment of cholestatic pruritus in Alagille syndrome (ALGS) in patients aged 6 months or older. The European Commission will now consider the CHMP recommendations. Final decisions on marketing authorization for Iqirvo and for Kayfanda are anticipated in Q3, 2024.

Iqirvo and PBC : Iqirvo is a first-in-class, oral, peroxisome proliferator-activated receptor (PPAR) agonist. Iqirvo was in-licensed by Ipsen from Genfit in 2021. The CHMP positive opinion is based mainly on data from the Phase III ELATIVE trial. The composite endpoint was achieved with results demonstrating statistically significant improvements in alkaline phosphatase (ALP) and total bilirubin (TB), biomarkers of PBC disease progression. For the key secondary endpoint using the PBC Worst Itch NRS score a trend towards improvement in pruritus (itch) was observed for elafibranor versus placebo, which was not statistically significant. Two other secondary patient-reported outcome measures were used to assess itch, and greater reductions were observed with Iqirvo compared with placebo at Week 52, according to the itch domain of PBC-40 quality of life questionnaire (LS mean difference -2.3; 95% CI, -4.0 to -0.7) and 5-D Itch total score (LS mean difference, -3.0; 95% CI, -5.5 to -0.5).

“PBC is a progressive disease with a high number of patients who either don’t respond or can’t tolerate the current available treatments. This can result in ongoing disease progression, which may not be picked up until the patient’s next doctor’s appointment, which can be as long as 12 months between visits in some cases,” said Professor Marco Carbone, Professor of Gastroenterology, University of Milano-Bicocca and Consultant Hepatologist, the Niguarda Liver Transplant Centre, Milan. “It is important that we not only regularly review our PBC patients to ensure the levels of alkaline phosphatase, or ALP, and bilirubin are within normal limits, but that we also discuss symptoms that might impair patients’ quality of life potentially leading to withdrawal from current treatments.”

Kayfanda and Alagille Syndrome : Kayfanda’s CHMP positive opinion is based on the ASSERT Phase III clinical trial data, presented at the 2022 American Association for the Study of Liver Disease (AASLD) congress and recently published in Lancet Gastroenterology & Hepatology. ASSERT is the world’s first and only Phase III trial completed in patients with ALGS. The data demonstrated efficacy of odevixibat in pruritus, a measure of treatment benefit, based on the worst scratching score using an observer-reported outcome instrument. Results demonstrated statistically significant and clinically meaningful improvements from baseline to month 6, in scratching severity, for odevixibat versus placebo, which was seen rapidly and maintained over the study period.

“Effective and well-tolerated treatments that can manage the debilitating itch caused by Alagille Syndrome and reduce the concentration of bile acids in the blood, are of great importance in our management and care of children with this condition and it is a positive development that there may soon be a new treatment option available,” said Professor Henkjan Verkade, Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Groningen, Beatrix Children’s Hospital and University Medical Center Groningen, Netherlands. “This condition leads to multiple complications, it is however the intense itch experienced by these children and resulting sleep disturbances that is reported by the vast majority of people living with and caring for a child with liver disease due to Alagille Syndrome, as being the most significant.”

In the ASSERT trial efficacy was also demonstrated on the key secondary endpoint showing a statistically significant reduction in serum bile acid concentration at the end of treatment for patients on odevixibat compared to placebo. Consistent with the improvements observed in pruritus, treatment with odevixibat led to significant improvements in multiple observer-reported outcome sleep parameters. The overall incidence of treatment emergent adverse events with odevixibat was similar to placebo, with a low drug-related diarrhea rate in patients with ALGS. All patients completed the study and 50 out of 52 patients have joined the extension study with all receiving odevixibat.

In the ASSERT trial efficacy was also demonstrated on the key secondary endpoint showing a statistically significant reduction in serum bile acid concentration at the end of treatment for patients on odevixibat compared to placebo. Consistent with the improvements observed in pruritus, treatment with odevixibat led to significant improvements in multiple observer-reported outcome sleep parameters. The overall incidence of treatment emergent adverse events with odevixibat was similar to placebo, with a low drug-related diarrhea rate in patients with ALGS. All patients completed the study and 50 out of 52 patients have joined the extension study with all receiving odevixibat.

See-Kowdley. K.V, et al. "Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. NEJM. 2023. DOI: 10.1056/NEJMoa2306185."

See- Ovchinsky N., et al. "Efficacy and safety of odevixibat in patients with Alagille syndrome (ASSRT); a phase III, double-blind, randomized, placebo-controlled trial. Lancet Gastroenterol / Hepatol. 2024 doi.org/10.1016/S2468-1253(24)00074-8.,?p>