Mirum Awaits EMA Verdict On ‘Reprioritized’ Livmarli Filing
Executive Summary
Mirum could soon find out if its decision to reprioritize its EU filings for its rare liver disease drug has paid off.
Mirum Pharmaceuticals is set to learn whether its application for pan-EU marketing approval for its rare liver disease treatment, Livmarli (maralixibat), is likely to succeed.
The EU marketing authorization application (MAA) for the orphan drug is up for an opinion by the European Medicines Agency this week on whether it should be approved for treating cholestasis in patients with Alagille syndrome (ALGS) who are one year of age and older.
If authorized for cholestasis in ALGS, Livmarli will be the first pharmacologic treatment option in the EU for the disorder, which is a “devastating disease for which there is significant and urgent unmet need,” said Mirum president & CEO, Chris Peetz. Livmarli, an ileal bile acid transporter (IBAT) inhibitor, was approved in the US for cholestatic pruritus in patients with ALGS last year. (Also see "First-In-Class Drugs Made Up More Than Half Of US FDA’s Novel Approvals Last Year" - Pink Sheet, 7 Jan, 2022.)
The EU MAA was submitted to the EMA for review in September 2021. It replaced a previous MAA for the drug that Mirum had filed for treating progressive familial intrahepatic cholestasis type 2 (PFIC2) but then withdrew in the early stage of the review cycle for strategic reasons, with plans to refile later on.
“The decision to withdraw and resubmit was made after discussion with EMA reviewers on the proximity of PFIC Phase III data, and the strength of the ALGS data package to prioritize that application while waiting for the Phase III data,” Peetz told the Pink Sheet.
The plan was to re-submit for the PFIC indication “after the availability of results from the ongoing MARCH-PFIC Phase III study in a broader set of PFIC subtypes and with higher doses of maralixibat,” Peetz explained. Topline data evaluating more than 90 patients in the MARCH-PFIC Phase III clinical trial are expected to be announced in the fourth quarter of 2022.
If Livmarli is approved in the EU for cholestasis in ALGS, Peetz said: “Our strategy is to launch ourselves in Western Europe, which will begin Q1 next year, and leverage distributors to launch in Central and Eastern Europe.”
Cholestatic pruritus, otherwise known as severe itch, affects up to 88% of ALGS patients and is one of the most physically and emotionally debilitating symptoms of the disease and is a leading indication for liver transplant in ALGS, said the Mirum president & CEO. “The unrelenting itch has been described by some patients as “being set on fire” and often causes patients to scratch their skin to the point of bleeding and makes it difficult to sleep and do everyday tasks.”
Livmarli is among the products listed as being up for an opinion on the draft agenda of the latest monthly meeting of the EMA’s human medicines committee, the CHMP, as to whether they should be approved. The CHMP meeting runs from 10-13 October. (Also see "EU Moment of Truth For Abaloparatide & Advanced Therapy Tab-Cel" - Pink Sheet, 11 Oct, 2022.)
CHMP opinions are sent to the European Commission, which has 67 days to make a legally binding decision that is valid throughout the bloc.
Livmarli, an orally administered solution, is currently being evaluated in late-stage clinical studies in other rare cholestatic liver diseases including PFIC and biliary atresia.