Mirum’s Livmarli gets thumbs up from CHMP for treating PFIC in young patients

04-Jun-2024 - Last updated on 04-Jun-2024 at 13:26 GMT

Mirum Pharmaceuticals just got a major boost as the European Committee for Medicinal Products for Human Use (CHMP) gave a positive nod to Livmarli (maralixibat) oral solution for treating Progressive Familial Intrahepatic Cholestasis (PFIC) in patients aged three months and up.

This endorsement comes from the phase 3 March study showing a highly significant reduction in pruritus severity compared to placebo across all PFIC types.

The CHMP's assessment highlights that Livmarli offers significant clinical benefits over existing therapies. Additionally, the Committee for Orphan Medicinal Products (COMP) recommended maintaining the Orphan Drug Designation for Livmarli in PFIC. The European Commission's decision is expected in the third quarter of 2024.

“The positive and favorable opinions by both CHMP and COMP recognize 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,” said Chris Peetz, Mirum's CEO.

Mirum Pharmaceuticals' Livmarli

“Further, 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.”

These opinions are based on data from the phase 3 March study, the largest randomized trial in PFIC, involving 93 patients across various PFIC types, including PFIC1, PFIC2, PFIC3, PFIC4, PFIC6, and unidentified mutational status.

The study demonstrated a highly statistically significant reduction in pruritus severity between Livmarli and placebo across all PFIC types studied. This means that Livmarli has the potential to provide substantial relief to patients suffering from severe itching, which is one of the most debilitating symptoms of PFIC.

Livmarli is currently approved in Europe for treating cholestatic pruritus in patients with Alagille syndrome (ALGS) from two months old and in the US for patients with ALGS from three months old and for PFIC in those five years and older.

PFIC treatment

Mirum has also submitted a supplemental new drug application (sNDA) to introduce a higher concentration formulation of Livmarli for younger PFIC patients in the U.S. later this year. This new formulation, used during the March study, aims to enable label expansion to include younger patients, providing an effective treatment option for infants and toddlers affected by this rare liver disease.

Progressive Familial Intrahepatic Cholestasis (PFIC) is a rare genetic disorder that causes progressive liver disease typically leading to liver failure. In people with PFIC, liver cells are less able to secrete bile, leading to a buildup of bile in the liver, which causes liver disease. Symptoms of PFIC often begin in infancy and include severe itching (pruritus), jaundice (yellowing of the skin and eyes), failure to thrive, and liver failure.

The disease is estimated to affect one in every 50,000 to 100,000 births in the United States and Europe. More than six types of PFIC have been identified, all characterized by impaired bile flow and progressive liver disease.

The significance of the CHMP's positive opinion cannot be overstated, as it represents a crucial step towards making Livmarli available to a broader patient population in Europe. The CHMP's endorsement is a scientific recommendation to the European Commission for marketing authorization, and if approved, it will provide a new treatment option for patients suffering from this debilitating condition. The favorable opinion from COMP further supports the continued development and maintenance of orphan drug status for Livmarli, recognizing its potential to address an unmet medical need in a rare disease population.

CHMP positive opinion

Livmarli is an orally administered, once-daily ileal bile acid transporter (IBAT) inhibitor. It is designed to reduce the reabsorption of bile acids from the small intestine, thereby reducing bile acid levels in the liver and alleviating symptoms of cholestasis, such as pruritus. The positive results from the phase 3 March study highlight the potential of Livmarli to improve the quality of life for patients with PFIC by significantly reducing pruritus severity and other related symptoms.

In addition to its approval for PFIC, Livmarli is approved in Europe for the treatment of cholestatic pruritus in patients with ALGS from two months of age. In the United States, it is approved for treating cholestatic pruritus in patients with ALGS from three months of age and for cholestatic pruritus in patients with PFIC five years of age and older. Livmarli is also approved in other regions globally, further emphasizing its role as a critical treatment option for patients with these rare liver diseases.

European Commission approval

Mirum's ongoing efforts to expand the availability of Livmarli include submitting a supplemental new drug application (sNDA) in the U.S. to introduce a higher concentration formulation of the drug. This new formulation, used during the MARCH study, aims to enable label expansion to include younger patients with PFIC, providing an effective treatment option for infants and toddlers affected by this rare liver disease.

The positive opinions from CHMP and COMP mark a significant milestone for Mirum Pharmaceuticals and the PFIC community. With the potential European Commission approval on the horizon, patients and healthcare providers can look forward to having access to a new and effective treatment option for PFIC, offering hope for improved patient outcomes and quality of life.

This announcement marks a significant step forward in offering new hope for patients with PFIC, promising improved treatment options and better health outcomes for young patients.