Livmarli now approved in EU to treat adults, children with PFIC

Oral therapy already approved in Europe for Alagille syndrome patients

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Livmarli (maralixibat), an oral medication from Mirum Pharmaceuticals, is now approved in the European Union to treat progressive familial intrahepatic cholestasis (PFIC) in adults and children ages 3 months and older.

The marketing authorization granted by the European Commission follows a positive opinion from an advisory committee of the European Medicines Agency (EMA) to extend Livmarli’s label.

The therapy was first approved in the EU, as well as in the U.S., to ease itching caused by Alagille syndrome, a genetic disease that causes problems in the tubes that transport the digestive fluid bile from the liver to the intestines, and other hallmark features outside the liver.

The label expansion also follows a similar decision in the U.S., where Livmarli was approved for PFIC, but for patients ages 5 and older. The company has filed an application in the U.S. asking to extend the label to children as young as 3 months, and now awaits a decision by regulators.

“We are thrilled that the European Commission has granted marketing authorization for Livmarli in PFIC, acknowledging the strength of data collected and recognizing the important treatment opportunity for patients living with this rare liver disease,” Chris Peetz, Mirum’s CEO, said in a company press release. “Our hope is that Livmarli helps to improve key liver parameters and brings healthier days ahead to young patients diagnosed with PFIC in Europe.”

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The EMA’s Committee for Orphan Medicinal Products also recommended that Livmarli maintain its status as an orphan drug so it can benefit from up to 10 years of market exclusivity for the treatment of PFIC in the EU.

“It is encouraging to know that physicians in Europe will have a new option that has the potential to improve the liver health and quality of life for patients and their families,” said Richard J. Thompson, a professor of molecular hepatology at King’s College London in the U.K. Thompson was an investigator in the MARCH-PFIC study, whose data supported the label expansion.

PFIC is a rare liver disease that occurs due to genetic mutations; its different types depend on which gene is mutated. In all types, bile flow is slowed or stopped, a condition called cholestasis. Bile that can’t flow builds up in the liver, leading to damage, and leaks into the bloodstream, causing severe itching, known as pruritus.

Livmarli blocks the action of ileal bile acid transporter, a protein that helps bile acids return from the small bowel to the liver and the blood. Blocking this protein is expected to reduce bile buildup in the liver and increase its clearance through the intestines, thereby easing pruritus.

The therapy’s label expansion was largely based on positive data from MARCH-PFIC (NCT03905330), a global Phase 3 clinical trial that included 93 adults and children with various types of PFIC or even unclassified genetic mutations. The children ranged in age from 1 to 17.

The study tested Livmarli against a placebo, both given as an oral solution twice daily for 26 weeks, or about six months. Livmarli outperformed the placebo at easing pruritus and reducing the levels of bile acids in the blood as early as two weeks in, regardless of the patients’ underlying genetic mutation.

The most commonly reported adverse event with the therapy was diarrhea, which was temporary and mild in most cases.

PFIC can be life-altering and can have a devastating impact on patients. We are encouraged to see that young patients will have a new medication and hope for a life less burdened by cholestasis.

Longer-term data from MARCH-PFIC and its ongoing open-label extension study, dubbed MARCH-ON (NCT04185363), showed that Livmarli sustains benefits for up to two years. Patients who switched from the placebo to Livmarli as part of the extension study, which will last up to four years, saw similar benefits.

“The patient community in Europe will greatly benefit from Livmarli’s approval, supported by years of impressive data showing improvements in the most burdensome aspects of disease,” said Emily Ventura, executive director of the PFIC Network, a nonprofit that supports people living with PFIC and their families.

“PFIC can be life-altering and can have a devastating impact on patients. We are encouraged to see that young patients will have a new medication and hope for a life less burdened by cholestasis,” Ventura added.

Peetz acknowledged everyone who had a hand in the therapy’s development.

“We are grateful to the researchers, patients, and families who made this approval possible,” Peetz said.