Mirum Pharmaceuticals Announces Positive CHMP Opinion for LIVMARLI® (maralixibat) Oral Solution for Cholestatic Pruritus in Patients with Alagille Syndrome Two Months of Age and Older

- CHMP opinion based on pivotal ICONIC study with more than five years of data demonstrating durable and clinically meaningful improvements in cholestatic pruritus and serum bile acids for patients with Alagille syndrome (ALGS).

- Following CHMP recommendation, a decision by the European Commission is expected by year-end 2022; if approved, LIVMARLI would be the first medication to treat cholestatic pruritus for patients with ALGS in Europe.

- LIVMARLI also received approval by Israeli Ministry of Health for cholestatic pruritus in patients with Alagille syndrome one year of age and older; represents second regulatory approval in the indication and first approval outside of U.S.

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) today announced two global advancements for LIVMARLI® (maralixibat) oral solution, an oral minimally absorbed ileal bile acid transporter (IBAT) inhibitor currently approved in the U.S. for the treatment of cholestatic pruritus in patients with Alagille syndrome one year of age and older.

The European Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion of LIVMARLI for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) two months of age and older. The CHMP positive opinion is the scientific recommendation to the European Commission for grant marketing authorization in Europe. LIVMARLI was previously approved by the U.S. Food and Drug Administration in 2021 as the first and only treatment for cholestatic pruritus in patients with ALGS one year of age and older.

Mirum also announced that its partner, Neopharm, received commercial and marketing authorization by the Israeli Ministry of Health, Israel’s regulatory agency responsible for the approval of new medicines, granting approval of LIVMARLI for the treatment of cholestatic pruritus in patients with ALGS one year of age and older.

“LIVMARLI is the first and only medicine to receive CHMP positive opinion to address cholestatic pruritus in patients with Alagille syndrome and we are hopeful that this medication provides a meaningful treatment option for people suffering from this devastating disease,” said Chris Peetz, president and chief executive officer at Mirum. “Our experience with LIVMARLI in the U.S. has shown the impact it can have on the lives of patients and their families living with ALGS. We are eagerly preparing for the launch of LIVMARLI in Europe and are excited about the opportunity to further expand LIVMARLI’s availability globally, which is off to a great start with the recent approval in Israel.”

ALGS is a rare genetic disease caused by abnormalities in bile ducts that can lead to progressive liver disease. Malformed or reduced bile ducts cause retention of bile acids in the liver leading to cholestasis and ultimately inflammation and liver injury which prevents the liver from working properly. Cholestasis in ALGS leads to a debilitating pruritus impacting the quality of life so significantly that pruritus is a leading indication for liver transplantation.

The positive CHMP opinion is based on data from the pivotal ICONIC study including five years of data across the LIVMARLI clinical program resulting in a robust body of evidence in patients with ALGS. Data from ICONIC demonstrated statistically significant and clinically meaningful reductions in pruritus compared to placebo with a mean difference of -1.4 points between groups, as well as significant reductions in serum bile acids, both of which were durably maintained over several years of treatment. The proposed label also includes reductions in xanthoma severity.

The European Commission’s endorsement of the CHMP positive opinion is expected in the fourth quarter of 2022. If approved in Europe, LIVMARLI would be the first and only approved treatment to address the effects of Alagille syndrome, a rare and devastating liver disease impacting 1 out of 30,000 people globally.

“The positive opinion adopted by the CHMP is an important step forward in the treatment of cholestatic pruritus for people living with Alagille syndrome, given the lack of treatments to effectively address this terrible disease burden which can ultimately lead to a decision for liver transplantation,” said Professor Emmanuel Jacquemin, MD, PhD, Head of Pediatric Hepatology and Liver Transplantation Unit, Bicêtre Hospital, AP-HP, Paris-Saclay University, Le Kremlin-Bicêtre, France. “We are excited about the potential approval and availability of LIVMARLI for patients in Europe.”

“Alagille syndrome is seen in patients globally. Outside the U.S. only limited treatment options have been available until now to effectively help people deal with the debilitating effects of the disease, especially pruritus. Pruritus causes significant disruptions to the lives of both patients and their family members,” said Roberta Smith, president of the Alagille Syndrome Alliance. “We are thrilled that there is hope on the near horizon for people with Alagille syndrome in Europe and are optimistic that LIVMARLI may provide relief to those suffering from cholestatic pruritus in ALGS if approved, much like we’ve heard from our U.S. families following LIVMARLI’s launch in the United States."

About Alagille Syndrome

Alagille syndrome (ALGS) is a rare genetic disorder in which bile ducts are abnormally narrow, malformed and reduced in number, which leads to bile accumulation in the liver and ultimately progressive liver disease. The estimated incidence of ALGS is one in every 30,000 people.¹ In patients with ALGS, multiple organ systems may be affected by the mutation, including the liver, heart, kidneys and central nervous system.² The accumulation of bile acids prevents the liver from working properly to eliminate waste from the bloodstream and, according to recent reports, 60% to 75% of patients with ALGS have a liver transplant before reaching adulthood.³ Signs and symptoms arising from liver damage in ALGS may include jaundice (yellowing of the skin), xanthomas (disfiguring cholesterol deposits under the skin), and pruritus (itch)². The pruritus experienced by patients with ALGS is among the most severe in any chronic liver disease and is present in most affected children by the third year of life.⁴

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) one year 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.

LIVMARLI is currently being evaluated in late-stage clinical studies in other rare cholestatic liver diseases including progressive familial intrahepatic cholestasis (PFIC) and 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 bone fractures and gastrointestinal bleeding.

Prescribing information

About Mirum Pharmaceuticals

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 one year of age and older. In Europe, the European Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for LIVMARLI for the treatment of cholestatic pruritus in patients with Alagille syndrome two months of age and older. A decision by the European Commission is expected by year-end 2022.

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 MARCH Phase 3 clinical trial for progressive familial intrahepatic cholestasis (PFIC) and 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 three potentially registrational studies including the VISTAS Phase 2b clinical trial for adults with primary sclerosing cholangitis, the OHANA Phase 2b clinical trial for pregnant women with intrahepatic cholestasis of pregnancy, and the VANTAGE Phase 2b clinical trial for adults with primary biliary cholangitis.

Follow Mirum on Twitter, Facebook, LinkedIn and Instagram.

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 commercialization plans and expectations for commercializing LIVMARLI in potential available markets, estimates of the number of patients impacted by ALGS and who are appropriate for treatment with LIVMARLI, the potential benefits or competitive position of LIVMARLI, the timing of ongoing and planned clinical trials and the regulatory approval process of maralixibat in other indications and jurisdictions and similar potential of volixibat. 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.

¹Danks, et al. Archives of Disease in Childhood1977
²Johns Hopkins Medicine. hopkinsmedicine.org/health/conditions-and-diseases/Alagille-syndrome
³Vandriel, et al. GALA EASL 2020; Kamath, et al. Hepatology Communications 2020
⁴Elisofon, et al. Journal of Pediatric Gastroenterology and Nutrition 2010