First treatment for rare liver disease

News 21/05/2021

EMA has recommended granting a marketing authorisation in the European Union for Bylvay (odevixibat) for the treatment of Progressive Familial Intrahepatic Cholestasis (PFIC) in patients aged 6 months or older.

PFIC is a rare, life-threatening liver disease. Patients have liver cells that are less able to secrete bile (a fluid produced in the liver that helps to break down fats). The build-up of bile in liver cells causes liver disease. The symptoms typically develop in infancy, usually in the first months of life. Approximately only half of the children affected by the disease survive beyond the age of 10 years.

Severe itching (pruritus) is common in children diagnosed with PFIC. This can lead to sometimes serious scratching injuries, loss of sleep, irritability and poor attention.

There is a high unmet need for these patients whose treatment options are limited to surgical intervention and off-label symptomatic medical therapies. If untreated, many PFIC patients progress to end-stage liver disease and require liver transplantation.

The active substance of Bylvay is odevixibat, a reversible, potent, selective inhibitor of the ileal bile acid transporter (IBAT) that acts locally in the distal ileum (last part of the small intestine), reducing the reuptake of bile acids and increasing the clearance of bile acids through the colon.

The main study on which the recommendation by EMA’s human medicines committee (CHMP) is based was a double-blind, randomized, placebo-controlled phase 3 study, which investigated the efficacy and safety of Bylvay in children with PFIC. The results showed a significant reduction in serum bile acids accompanied by a significant reduction in pruritus in patients treated with odevixibat. These results were maintained in an ongoing, long-term open-label follow-up study. Hepatic parameters and fibrosis scores were improving or were stable for the duration of the study (max. 72 weeks). However, more data are needed to determine if odevixibat can delay disease progression and the need for liver transplantation. The CHMP therefore requested a registry-based efficacy study as a follow-up.

The most common side effects are diarrhoea, abdominal pain, haemorrhagic diarrhoea, soft faeces, and hepatomegaly (enlarged liver).

No clinically significant differences in the pharmacokinetic, safety and tolerability profile of odevixibat were observed based on age, sex or race.

The medicine was accepted in EMA’s PRIME scheme, that offers extra support to developers of medicines that have the potential to address patients' unmet medical needs. The CHMP reviewed the application for Bylvay under its accelerated assessment procedure, which allows the speeding up of patients' access to medicines.

As PFIC is a very rare disease, the CHMP agreed that it is not possible to provide comprehensive data on the efficacy under normal conditions of use. Therefore, the Committee recommended granting a marketing authorisation under exceptional circumstances and requested the applicant to complete a registry-based study to further characterise the efficacy of Bylvay in patients aged 6 years or older.

A marketing authorisation under exceptional circumstances allows patients access to medicines that cannot be approved using a standard authorisation route as comprehensive data cannot be obtained, either because there are only very few patients with the disease, the collection of complete information on the efficacy and safety of the medicine would be unethical, or there are gaps in the scientific knowledge. These medicines are subject to specific post-authorisation obligations and monitoring.

The opinion adopted by the CHMP is an intermediary step on Bylvay’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role/use of this medicine in the context of the national health system of that country.


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