EMA committee favors approval of Livmarli for PFIC in EU

European Commission's decision expected later this year

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Mirum Pharmaceuticals has received a positive opinion from an arm of the European Medicines Agency (EMA) to extend the approval of Livmarli (maralixibat) in Europe to people, 3 months and older, with progressive familial intrahepatic cholestasis (PFIC).

The opinion from the EMA’s Committee for Medicinal Products for Human Use (CHMP) is forwarded to the European Commission, which has the authority to grant a license for marketing throughout Europe. A decision is expected later this year.

Livmarli is currently approved in Europe for cholestatic pruritus, or itching, in people with Alagille syndrome, 2 months and older. In the U.S., it’s approved for cholestatic pruritus in people 3 months and older, with Alagille syndrome, and in those 5 and older with any type of PFIC, except type 2.

“We are thrilled that, if approved by the European Commission, the PFIC community will have a treatment option that has been shown to significantly improve key liver health parameters starting from three months of age,” Chris Peetz, Mirum’s CEO, said in a company press release.

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Another EMA committee recommends Livmarli maintain its orphan drug status

The EMA’s Committee for Orphan Medicinal Products (COMP) also adopted a positive opinion recommending that Livmarli maintain its orphan drug status so it can benefit from 10 years of protection from competition once — and if — it receives a marketing license for PFIC.

“The positive and favorable opinions by both CHMP and COMP recognizes the potential of Livmarli in treating patients with PFIC in Europe, underscoring the compelling long-term data collected in the largest PFIC study across a broad range of genetic types,” Peetz said.

There are several types of PFIC, each associated with mutations in different genes. In all types, a digestive fluid called bile cannot flow out of the liver and builds up, causing damage. When bile builds up in the bloodstream or skin, it can cause pruritus.

Available as an oral solution, Livmarli blocks the action of a protein called ileal bile acid transporter. This prevents bile acids from going back to the blood and liver, while increasing the amount of bile that’s removed from the body in the feces. As a result, bile doesn’t build up as much, which is expected to ease pruritus.

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Positive opinions based on findings of Phase 3 MARCH-PFIC trial

The positive opinions draw on findings from the Phase 3 MARCH-PFIC trial (NCT03905330), which stands as the broadest clinical study carried out for PFIC. It included 93 children and adolescents, ages 1 to 17, with various types of PFIC, including PFIC1, PFIC2, PFIC3, PFIC4, PFIC6, and some with unclassified genetic mutations.

Patients were randomly assigned to receive either Livmarli or a placebo twice daily for 26 weeks, or about six months. Livmarli was found to outperform the placebo at reducing pruritus severity and the levels of bile acids in the blood as early as after two weeks, regardless of PFIC type.

Additional data from MARCH-PFIC and its open-label extension, MARCH-ON (NCT04185363), showed that Livmarli continues to have benefits for up to two years while being generally safe. Patients who switched from a placebo to Livmarli as part of MARCH-ON also saw similar benefits.

In the U.S., Mirum has filed a supplemental new drug application asking regulators to approve a higher strength of Livmarli, as used during MARCH-PFIC in younger patients, to extend the label to PFIC patients as young as 3 months. A decision is expected later this year.