Mirum Submits for European Approval of LIVMARLI in Progressive Familial Intrahepatic Cholestasis

Rhea-AI Summary

Mirum Pharmaceuticals has submitted a variation application to the European Medicines Agency (EMA) to extend the Marketing Authorization for LIVMARLI (maralixibat) to treat progressive familial intrahepatic cholestasis (PFIC) in patients aged two months and older. This is based on data from the Phase 3 MARCH study, the largest trial for PFIC, showing significant improvements in serum bile acids, pruritus, bilirubin, and growth metrics. LIVMARLI is already approved for treating cholestatic pruritus associated with Alagille syndrome. The company also submitted a supplemental application to the U.S. FDA for similar use in PFIC patients three months and older.

Positive

• Submission for EMA Marketing Authorization variation to expand LIVMARLI's treatment indications for PFIC patients two months and older.
• Data from the Phase 3 MARCH study highlights statistically significant improvements in key health metrics, indicating strong clinical efficacy.
• LIVMARLI already holds approvals for Alagille syndrome, creating a pathway for broader patient access if approved for PFIC.

Negative

• None.

• Marketing Authorization variation submitted for treatment of patients with progressive familial intrahepatic cholestasis (PFIC) two months of age and older; data supports treatment across the broadest range of genetic types ever studied.
  
  
  
  

• Application based on statistically significant and clinically meaningful improvements in serum bile acids, pruritus, bilirubin, and growth from the Phase 3 MARCH study.
  
  
  
  

• Supplemental new drug application for LIVMARLI previously submitted to U.S. FDA for treatment of cholestatic pruritus in patients with PFIC.

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM) today announced submission to the European Medicines Agency (EMA) of a variation application to the Marketing Authorization for LIVMARLI^® (maralixibat) oral solution, to extend the label for progressive familial intrahepatic cholestasis (PFIC) in patients two months of age and older. LIVMARLI is currently approved by the EMA for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) two months of age and older.

The submission is based on data from the Phase 3 MARCH study of LIVMARLI in patients with PFIC. MARCH is the largest randomized trial conducted in PFIC, with 93 patients across a broad range of genetic PFIC types, including PFIC1, PFIC2, PFIC3, PFIC4, PFIC6 and unidentified mutational status. In the cohort evaluating combined genetic types, LIVMARLI-treated patients had statistically significant improvements in pruritus (p< 0.0001), serum bile acids (p<0.0001), bilirubin (p=0.0471), and growth as measured by weight z-score (p=0.0391). The variation also included interim analysis data from the ongoing open-label extension study (MARCH-ON) which included 85 of the 93 patients that were enrolled in the pivotal trial. Overall, LIVMARLI demonstrated maintenance of treatment effect with sustained reductions in serum bile acid and bilirubin levels as well as continuous pruritus improvement. Growth acceleration was further improved throughout the follow-up indicating catch-up growth in children with PFIC.

“The expansive data we have collected from our PFIC studies give us great confidence that, if approved by the EMA, LIVMARLI will provide an impactful treatment option for patients across a broad range of genetic types, including those with phenotypic diagnosis but without a known variant,” said Chris Peetz, president and chief executive officer at Mirum. “We have now submitted these groundbreaking data to regulatory agencies in the U.S. and Europe with the hope of making LIVMARLI available to PFIC patients across multiple geographies. We are grateful to the clinicians and families who participated in the research that has meaningfully advanced treatment for PFIC.”

LIVMARLI is currently approved in the United States and Europe for the treatment of cholestatic pruritus in patients with Alagille syndrome three months of age and older, and two months of age and older, respectively. In addition to the Marketing Authorization variation announced today, Mirum has also submitted a supplemental new drug application to the U.S. FDA for the treatment of cholestatic pruritus in patients three months of age and older with PFIC. Regulatory submissions outside of the U.S., Canada and Europe are being pursued by partners and distributors in key markets globally.

About LIVMARLI^® (maralixibat) oral solution

LIVMARLI^® (maralixibat) oral solution is an orally administered, once-daily, ileal bile acid transporter (IBAT) inhibitor approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) three months of age and older and is the only FDA-approved medication to treat cholestatic pruritus associated with Alagille syndrome. For more information, please visit LIVMARLI.com.

Mirum has also submitted LIVMARLI for approval in the U.S. (in cholestatic pruritus in PFIC patients three months of age and older) and in Europe (in PFIC for patients two months of age and older).

LIVMARLI is currently being evaluated in late-stage clinical studies in other rare cholestatic liver diseases including biliary atresia. LIVMARLI has received Breakthrough Therapy designation for ALGS and PFIC type 2 and orphan designation for ALGS, PFIC and biliary atresia. To learn more about ongoing clinical trials with LIVMARLI, please visit Mirum’s clinical trials section on the company’s website.

IMPORTANT SAFETY INFORMATION

LIVMARLI can cause side effects, including:

Changes in liver tests. Changes in certain liver tests are common in patients with Alagille syndrome and can worsen during treatment with LIVMARLI. These changes may be a sign of liver injury and can be serious. Your healthcare provider should do blood tests before starting and during treatment to check your liver function. Tell your healthcare provider right away if you get any signs or symptoms of liver problems, including nausea or vomiting, skin or the white part of the eye turns yellow, dark or brown urine, pain on the right side of the stomach (abdomen) or loss of appetite.

Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea, stomach pain, and vomiting during treatment. Tell your healthcare provider right away if you have any of these symptoms more often or more severely than normal for you.

A condition called Fat Soluble Vitamin (FSV) Deficiency caused by low levels of certain vitamins (vitamin A, D, E, and K) stored in body fat. FSV deficiency is common in patients with Alagille syndrome but may worsen during treatment. Your healthcare provider should do blood tests before starting and during treatment.

Other common side effects reported during treatment were gastrointestinal bleeding and bone fractures.

US Prescribing Information

EU SmPC

About Mirum Pharmaceuticals, Inc.

Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare liver diseases. Mirum’s approved medication is LIVMARLI^® (maralixibat) oral solution which is approved in the U.S. for the treatment of cholestatic pruritus in patients with Alagille syndrome three months of age and older, and in Europe for the same indication in patients two months of age and older. Mirum has submitted LIVMARLI for approval in the U.S. (in cholestatic pruritus in PFIC for patients three months and older) and in Europe (in PFIC for patients two months and older).

Mirum’s late-stage pipeline includes two investigational treatments for debilitating liver diseases affecting children and adults. LIVMARLI, an oral ileal bile acid transporter (IBAT) inhibitor, is currently being evaluated in clinical trials for pediatric liver diseases and includes the EMBARK Phase 2b clinical trial for patients with biliary atresia. In addition, Mirum has an expanded access program open across multiple countries for eligible patients with ALGS and PFIC.

Mirum’s second investigational treatment, volixibat, an oral IBAT inhibitor, is being evaluated in two potentially registrational studies including the VISTAS Phase 2b clinical trial for adults with primary sclerosing cholangitis and the VANTAGE Phase 2b clinical trial for adults with primary biliary cholangitis.

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Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the expectations for commercializing LIVMARLI in the European Union with an expanded label, the regulatory acceptance of the MARCH trial data and the potential real world benefit of LIVMARLI outside of a clinical study. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Mirum’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Mirum’s business in general, the impact of the COVID-19 pandemic, and the other risks described in Mirum’s filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Mirum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20230405005395/en/

Media Contact:

Erin Murphy

media@mirumpharma.com

Investor Contacts:

Andrew McKibben

ir@mirumpharma.com

Sam Martin

Argot Partners

ir@mirumpharma.com

Source: Mirum Pharmaceuticals, Inc.

FAQ

What is the significance of the EMA submission for Mirum Pharmaceuticals?

The EMA submission aims to expand the treatment indication of LIVMARLI for progressive familial intrahepatic cholestasis (PFIC) patients aged two months and older.

What data supports the application for LIVMARLI in PFIC patients?

The application is based on results from the Phase 3 MARCH study, which demonstrated significant improvements in serum bile acids, pruritus, bilirubin, and growth.

When was the LIVMARLI application submitted to the EMA?

The application was announced recently but the specific date is not detailed in the press release.

What other regulatory submissions has Mirum Pharmaceuticals made for LIVMARLI?

In addition to the EMA submission, Mirum has submitted a supplemental new drug application to the U.S. FDA for treating cholestatic pruritus in PFIC patients aged three months and older.

What is the stock symbol for Mirum Pharmaceuticals?

The stock symbol for Mirum Pharmaceuticals is MIRM.