Ipsen’s stock has fallen after its rare disease drug Bylvay (odevixibat) failed to show benefit in a Phase III trial in biliary atresia (BA) patients.
In the randomised, double-blind, placebo-controlled BOLD trial (NCT04336722), Bylvay was investigated in BA patients who had already undergone surgical treatment with a Kasai hepatoportoenterostomy (HPE).
Go deeper with GlobalData
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
While not sharing data, Ipsen confirmed the trial did not meet the primary endpoint of improvement in native liver survival versus placebo.
The safety profile of Bylvay remained in line with that of the drug’s other approved indications. The study enrolled 254 patients across 19 countries who had undergone surgery within the first 90 days of their lives.
BA is the leading cause of paediatric liver transplant, with no approved therapeutic options beyond Kasai HPE or liver transplant surgery. It affects one in 5,000-20,000 newborns, in which the bile ducts inside and/or outside the liver are blocked, absent, or scarred, preventing bile from draining into the intestine. Currently there are no approved medical treatment options for BA.
Lead investigator Dr Saul Karpen, paediatric hepatologist and chief scientific officer of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, said: “BA is a rare and serious liver disease that affects babies. Progressing rapidly and with no effective medical treatments, many children develop severe liver damage, and BA remains the number one cause of liver transplantation in children, often before the age of two. Research remains limited, leaving patients, families and clinicians with very few therapeutic options.”
Karpen added, however, that this trial has “produced valuable insights that will deepen our understanding of biliary atresia and provide a crucial basis for future research”.
Bylvay is a once-daily selective and potent ileal bile acid transport (IBAT) inhibitor that reduces bile acid reabsorption in the intestine. Through IBAT inhibition, the bile acids are instead diverted and excreted with faeces.
The drug has US Food and Drug Administration (FDA) approval for cholestatic pruritus in Progressive Familial Intrahepatic Cholestasis (PFIC) across all types, and for pruritus in patients with Alagille Syndrome (ALGS).
In the EU, Bylvay is approved for the treatment of PFIC, with orphan exclusivity granted, and is additionally marketed as Kayfanda for ALGS.
The drug generated €180m ($205.2m) for Ipsen in 2025, a 32.5% rise on the €135.9m generated in 2024.
An ongoing open-label extension study (BOLD-EXT) is evaluating the longer-term safety and efficacy of odevixibat in patients who have completed the BOLD trial. A decision regarding the continuation of patients in the open-label extension will be made following a comprehensive review of the full trial data.
Success in Ipsen’s BOLD trial would have been meaningful for patients given the lack of approved therapies.
Investors have reacted to this, with Ipsen’s stock dropping 3.25% after the failure was announced, from €163.00 ($185.75) at market close on 23 July to €157.70 at market open on 24 July. Ipsen, listed on the Paris exchange, has a market cap of €13.1bn.
This failure follows a similar outcome for Mirium Pharmaceuticals in 2023. Mirium’s Livmarli (maralixibat), which is also an IBAT inhibitor, failed to show benefit in the Phase II EMBARK trial.
