IQIRVO (elafibranor) - Primary biliary cholangitis

The Committee deems the clinical benefit of IQIRVO (elafibranor) is moderate in the MA indication. The Committee makes maintenance of the moderate clinical benefit conditional on its reassessment based on the results of the phase 3 confirmatory study (ELFIDENCE CLIN-60190-454 study) required by the EMA in the context of the conditional MA.

Considering:

• an adapted development plan in primary biliary cholangitis for elafibranor, with two randomised controlled studies (phase 3 pivotal study and phase 3 confirmatory study ongoing), with efficacy results in favour of elafibranor, but in comparison with placebo, concerning an interim endpoint (alkaline phosphatase and bilirubin levels),
• a reassuring safety profile based on the available data,

but also:

• a low effect size for normalisation of alkaline phosphatase (more relevant biochemical endpoint) and the absence of an established effect on bilirubin levels (relevant endpoint) of elafibranor in comparison with placebo,
• the lack of evidence of efficacy on pruritus (highly incapacitating symptom) in comparison with placebo,
• the absence of established efficacy on disease progression endpoints, in particular clinical events or transplantation-free survival (relevant assessment endpoints),
• the lack of comparative data versus bezafibrate (used off-label, but recommended by experts), which is a clinically relevant comparator in second-line treatment,

the Committee considers that, on the basis of currently available data, IQRVO 80 mg film-coated tablets (elafibranor) provides no clinical added value (CAV V) in the current care pathway, in combination with ursodeoxycholic acid (UDCA) in adults with primary biliary cholangitis with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA.