Ipsen has achieved an unprecedented regulatory milestone, securing positive opinions from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) for two rare liver disease treatments on the same day. The French pharmaceutical company received approval for odevixibat under the new brand name Kayfanda for Alagille syndrome (ALGS) and for Iqirvo (elafibranor) as a treatment for primary biliary cholangitis (PBC).
Strategic Rebranding Overcomes Regulatory Hurdles
The approval of odevixibat for ALGS represents an unusual regulatory journey. The once-daily, non-systemic ileal bile acid transport (IBAT) inhibitor previously received CHMP recommendation in July 2023 under the Bylvay brand for the same indication. However, Ipsen was unable to secure orphan status for the drug, which provides crucial reimbursement advantages and 10 years of marketing exclusivity in EU member states.
Ipsen's solution involved refiling the drug under the new Kayfanda brand name, requiring a complete new marketing application. The company's head of R&D, Christelle Huguet, had previously expressed disappointment with the Committee for Orphan Medicinal Products (COMP) decision, stating that "the current approach to assessing 'significant benefit' threatens to undermine the aims of this regulation."
Clinical Evidence Supports ALGS Treatment
Odevixibat targets the debilitating itching caused by ALGS, a rare disease resulting from mutations in the JAG1 gene that leads to liver damage and jaundice. Itching is widely acknowledged as one of the most debilitating symptoms of the disease, particularly affecting young children and serving as a primary driver for patients seeking liver transplants.
The drug's efficacy was demonstrated in the ASSERT trial, which Ipsen describes as "the world's first and only phase 3 trial completed in patients with ALGS." The study showed that odevixibat achieved statistically significant and "clinically meaningful" improvements in scratching severity compared to placebo over six months.
Dual PPAR Agonist Addresses PBC Market
Simultaneously, Ipsen received CHMP approval for Iqirvo (elafibranor), a dual PPAR alpha/delta agonist for primary biliary cholangitis. The drug is recommended for use in combination with ursodeoxycholic acid (UDCA) in adults with inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.
PBC affects approximately 100,000 people in the United States, primarily women, with prevalence increasing. The chronic autoimmune disease gradually destroys bile ducts in the liver, potentially leading to cirrhosis. Patients experience debilitating fatigue and pruritus, and without treatment, the condition can progress to serious liver disease requiring transplantation.
Clinical trials demonstrated that Iqirvo reduces levels of PBC biomarkers, with a trend toward reduced itching. The drug received FDA approval in June and competes with Intercept Pharma's Ocaliva (obeticholic acid) in the PBC market.
Strategic Acquisitions Drive Portfolio Expansion
Ipsen acquired rights to odevixibat through its $950 million acquisition of Albireo in a $42-per-share deal. The drug is already approved in the EU under the Bylvay brand for progressive familial intrahepatic cholestasis (PFIC) and received FDA approval for ALGS in June 2023 with orphan status in the US market.
Previous estimates suggest odevixibat could generate over $1 billion in sales across its approved indications of PFIC, ALGS, and the potential future indication of biliary atresia (BA).
Iqirvo was acquired from Genfit in 2021 for an upfront payment of €120 million and up to €360 million in potential milestones, following positive phase 2 results for PBC treatment. Analysts estimate the market for UDCA-refractory PBC treatments could exceed $1.5 billion annually.
Rare Regulatory Achievement
Huguet characterized the dual CHMP approvals as "a rare achievement, and one that demonstrates our commitment to addressing the unmet medical needs in these diseases." The simultaneous approvals represent an uncommon regulatory success, particularly given the complex rebranding strategy required for odevixibat.
Both treatments address significant gaps in rare cholestatic liver disease management, with odevixibat providing the first targeted therapy for ALGS-related pruritus and Iqirvo offering an alternative treatment option for PBC patients with inadequate response to standard therapy.
