Mirum Pharmaceuticals’ LIVMARLI Approved in the European Union for Patients with PFIC

Rhea-AI Summary

The European Commission has granted marketing authorization for Mirum Pharmaceuticals' LIVMARLI (maralixibat) oral solution to treat progressive familial intrahepatic cholestasis (PFIC) in patients aged three months and older. This approval follows the positive opinion from the CHMP, noting LIVMARLI's significant clinical benefits over existing PFIC treatments. The decision also aligns with a positive COMP opinion recommending the continuation of Orphan Drug Designation for LIVMARLI in PFIC. Approval is based on data from the Phase 3 MARCH study, the largest randomized trial in PFIC, showing substantial reductions in pruritus and serum bile acids with LIVMARLI compared to placebo. The study included 93 patients with various genetic types of PFIC. Common adverse events were mild and transient diarrhea. LIVMARLI is also approved in the U.S. for treating cholestatic pruritus in PFIC patients aged five years and older.

Positive

• European Commission grants marketing authorization for LIVMARLI in PFIC.
• Approval based on positive CHMP and COMP opinions.
• Phase 3 MARCH study shows significant clinical benefits in reducing pruritus and serum bile acids.
• Largest randomized trial in PFIC with 93 patients.
• LIVMARLI is also approved in the U.S. for PFIC patients aged five and older.

Negative

• Common adverse event: mild and transient diarrhea.

Medical Research Analyst

The approval of LIVMARLI by the European Commission for the treatment of progressive familial intrahepatic cholestasis (PFIC) is a significant milestone. PFIC is a rare genetic liver disorder causing severe liver damage and pruritus (itching). This approval is based on robust data from the Phase 3 MARCH study, which demonstrated a statistically significant reduction in pruritus and serum bile acids, critical indicators of disease severity. The study included 93 patients with various genetic types of PFIC, showcasing the broad potential of LIVMARLI across multiple PFIC subtypes.

For patients and physicians, this approval means access to a treatment that provides meaningful clinical benefits, particularly in reducing the burdensome symptoms of PFIC. The maintenance of the Orphan Drug Designation also highlights the therapy's importance for a rare condition with limited treatment options.

Short-term, patients will have an effective alternative to existing therapies, potentially improving their quality of life. Long-term, the treatment could slow disease progression and improve overall liver health. These outcomes are based on the strong safety and efficacy profile presented, with diarrhea being the most common but manageable adverse event.

Financial Analyst

Mirum Pharmaceuticals' stock could see positive short-term movement following the European Commission's approval of LIVMARLI. This approval opens up a significant market for the company, potentially translating into increased revenues. The Phase 3 MARCH study results underpin the drug's efficacy, which is essential for market penetration and acceptance among healthcare professionals.

From a financial perspective, the Orphan Drug Designation not only underscores the therapy's value but also provides certain incentives, such as market exclusivity in the EU, which can enhance profitability. Investors should note that while the approval is a positive catalyst, the actual revenue impact will depend on the drug's adoption rate among European healthcare providers. Given the rare nature of PFIC, the patient population is limited, but the high unmet medical need may command a premium pricing strategy.

In the short-term, the approval boosts investor confidence and stock performance. In the long-term, sustainable revenue growth will depend on the drug's market uptake and potential label expansions, such as the expected feedback from the FDA on a higher concentration formulation for younger patients.

• European Commission grants LIVMARLI marketing authorization for treatment of PFIC in patients three months and older.
• Approval follows positive opinion from CHMP concluding LIVMARLI’s clinical benefit over existing therapy in PFIC.
• LIVMARLI also received positive COMP opinion recommending maintenance of Orphan Drug Designation in PFIC.

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) today announced that the European Commission has granted marketing authorization for LIVMARLI® (maralixibat) oral solution for the treatment of progressive familial intrahepatic cholestasis (PFIC) in patients three months of age and older. The approval follows a positive opinion by the CHMP which concluded that LIVMARLI in PFIC brings significant clinical benefit based on improved efficacy and a major contribution to patient care compared to the existing approved treatment for PFIC. Further, evaluation by COMP recommended maintenance of Orphan Drug Designation for LIVMARLI in PFIC.

The approval is based on data from the Phase 3 MARCH study, the largest randomized trial conducted in PFIC, with 93 patients across a range of genetic PFIC types, including PFIC1, PFIC2, PFIC3, PFIC4, PFIC6, and unidentified mutational status. Data from MARCH showed statistically significant reduction in pruritus (p<0.0001) and serum bile acids (p<0.0001) between LIVMARLI versus placebo in the All-PFIC cohort (n=64). Significant improvements were also observed in total bilirubin and growth versus placebo. The most common treatment emergent adverse event was diarrhea, which was predominantly mild, with no severe cases, and transient.

“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,” said Chris Peetz, chief executive officer at Mirum. “Our hope is that LIVMARLI helps to improve key liver parameters and brings healthier days ahead to young patients diagnosed with PFIC in Europe. We are grateful to the researchers, patients, and families who made this approval possible.”

“LIVMARLI’s approval provides a treatment backed by years of clinical research and meaningful data that demonstrate a reduction in cholestatic itch and prognostic markers of improved liver health, including a reduction of serum bile acids, all important signals for positive long-term outcomes,” said Professor Richard Thompson, King’s College London. “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.”

“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, PFIC Network. “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.”

LIVMARLI is also approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients with PFIC five years of age and older. Mirum has submitted a supplemental new drug application to introduce a higher concentration formulation of LIVMARLI, used during the MARCH study, to enable label expansion for younger patients with PFIC, and expects to receive FDA feedback this year.

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 for progressive familial intrahepatic cholestasis (PFIC) five years of age and older.

LIVMARLI is also the only approved IBAT inhibitor approved by the European Commission for the treatment of cholestatic pruritus in patients with ALGS two months and older, and by Health Canada for the treatment of cholestatic pruritus in ALGS. For more information for U.S. residents, please visit LIVMARLI.com.

LIVMARLI has received Breakthrough Therapy designation for ALGS and PFIC type 2 and orphan designation for ALGS and PFIC. To learn more about ongoing clinical trials with LIVMARLI, please visit Mirum’s clinical trials section on the company’s website.

IMPORTANT SAFETY INFORMATION

Limitation of Use: LIVMARLI is not for use in PFIC type 2 patients who have a severe defect in the bile salt export pump (BSEP) protein.

LIVMARLI can cause side effects, including:

Liver injury. Changes in certain liver tests are common in patients with Alagille syndrome and PFIC but can worsen during treatment. These changes may be a sign of liver injury. In PFIC, this can be serious or may lead to liver transplant or death. Your healthcare provider should do blood tests and physical exams 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), bloating in your stomach area, loss of appetite or bleeding or bruising more easily than normal.

Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea and stomach pain. Your healthcare provider may advise you to monitor for new or worsening stomach problems including stomach pain, diarrhea, blood in your stool or vomiting. 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 is common in patients with Alagille syndrome and PFIC but may worsen during treatment. Your healthcare provider should do blood tests before starting and during treatment and may monitor for bone fractures and bleeding which have been reported as common side effects.

US Prescribing Information
EU SmPC
Canadian Product Monograph

About Mirum Pharmaceuticals, Inc.

Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare diseases affecting children and adults. Mirum has three approved medications: LIVMARLI® (maralixibat) oral solution, CHOLBAM® (cholic acid) capsules, and CHENODAL® (chenodiol) tablets.

LIVMARLI, an IBAT inhibitor, is approved for the treatment of two rare liver diseases affecting children and adults. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome in the U.S. (three months and older), in Europe (two months and older), and in other regions globally. It is also approved in the U.S. in cholestatic pruritus in PFIC patients five years of age and older. CHOLBAM is FDA-approved for the treatment of bile acid synthesis disorders due to single enzyme deficiencies and adjunctive treatment of peroxisomal disorders in patients who show signs or symptoms or liver disease. CHENODAL has received medical necessity recognition by the FDA to treat patients with cerebrotendinous xanthomatosis (CTX).

Mirum’s late-stage pipeline includes two investigational treatments for debilitating liver diseases. Volixibat, an IBAT inhibitor, is being evaluated in two potentially registrational studies including the Phase 2b VISTAS study for primary sclerosing cholangitis and Phase 2b VANTAGE study for primary biliary cholangitis. Lastly, chenodiol, has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX, with positive topline results reported in 2023. Mirum has filed a new drug application with the FDA for the approval chenodiol to treat CTX in the U.S.

To learn more about Mirum, visit mirumpharma.com and follow Mirum on Facebook, LinkedIn, Instagram and Twitter (X).

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 commercial success of LIVMARLI in Europe for PFIC, pricing reimbursement for LIVMARLI in any specific country, and the real world impact of LIVMARLI in PFIC. 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,” “could,” “would,” “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. A further description of risks and uncertainties can be found in Mirum’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors,” as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240708474225/en/

Media Contact:

Erin Murphy

media@mirumpharma.com

Investor Contact:

Andrew McKibben

investors@mirumpharma.com

Source: Mirum Pharmaceuticals, Inc.

FAQ

What is LIVMARLI's approved use in the European Union?

LIVMARLI is approved for treating progressive familial intrahepatic cholestasis (PFIC) in patients aged three months and older.

What are the key findings from the Phase 3 MARCH study for LIVMARLI?

The Phase 3 MARCH study showed that LIVMARLI significantly reduces pruritus and serum bile acids in PFIC patients compared to a placebo.

What is the impact of the European Commission's approval on Mirum Pharmaceuticals' stock (MIRM)?

The approval could positively impact Mirum Pharmaceuticals' stock (MIRM) by expanding the market for LIVMARLI in the European Union, potentially increasing revenue.

What are the common side effects of LIVMARLI in PFIC treatment?

The most common side effect of LIVMARLI in PFIC treatment is mild and transient diarrhea.

Is LIVMARLI approved for treating PFIC in the United States?

Yes, LIVMARLI is approved by the FDA for treating cholestatic pruritus in PFIC patients aged five years and older.