Hepatology Publishes Six-Year Data Demonstrating Improved Clinical Outcomes in Patients with Alagille Syndrome Treated with Mirum’s LIVMARLI
Mirum Pharmaceuticals, Inc. (MIRM) announces a significant 70% risk reduction in long-term clinical outcomes for patients with Alagille syndrome (ALGS) treated with LIVMARLI. The data show a six-year transplant-free survival benefit, marking a milestone in pharmacological intervention.
The recent publication in Hepatology regarding Mirum Pharmaceuticals' LIVMARLI® treatment for Alagille syndrome (ALGS) marks a significant milestone in the management of this rare liver disease. The reported 70% risk reduction in long-term clinical outcomes, such as the need for liver transplantation, is a substantial improvement over the natural history control group. This figure is particularly notable given the rarity of ALGS and the limited treatment options historically available.
From a research perspective, the use of the Global Alagille Alliance (GALA) clinical database as a control is a robust methodological choice, ensuring a comprehensive comparison to untreated patients. The statistical significance (p<0.0001) indicates a low probability that the results are due to chance, reinforcing the potential of LIVMARLI as a transformative treatment option for ALGS patients.
The implications for healthcare systems and insurers are considerable. Potentially reducing the need for liver transplants, which are complex and costly procedures, could lead to significant cost savings and improved patient quality of life. Furthermore, the data could influence future research directions and healthcare policies regarding the management of cholestatic liver diseases.
The reported findings have profound economic implications for the healthcare industry, particularly in the context of rare diseases such as ALGS, where treatment advancements can drastically alter the cost landscape. The reduction in the need for liver transplants could translate into lower long-term healthcare costs, despite the initial investment in pharmacological intervention with LIVMARLI®.
Moreover, the improved transplant-free survival rate could decrease the economic burden on patients and their families, who often face significant indirect costs such as loss of income, travel for treatment and long-term care expenses. The ripple effect of this could be seen in reduced insurance premiums and a shift in resource allocation within healthcare systems.
It is important to analyze the cost-effectiveness of LIVMARLI® in the context of ALGS treatment. The long-term savings from avoided transplants and improved quality of life for patients must be weighed against the drug's pricing and the cost of managing any associated side effects. Such an analysis would be essential for payers and policymakers when considering the inclusion of LIVMARLI® in treatment protocols and insurance coverage.
The positive outcomes associated with LIVMARLI® could have a substantial impact on Mirum Pharmaceuticals' market position. The rarity of ALGS and the apparent efficacy of LIVMARLI® position it as a potential 'orphan drug,' which often commands premium pricing due to the lack of alternative treatments and the high value placed on disease mitigation.
Investors and stakeholders should closely monitor the adoption rate of LIVMARLI® post-publication of these results. Market penetration will depend on factors such as physician awareness, patient access and reimbursement policies. The success of LIVMARLI® could also pave the way for Mirum Pharmaceuticals to invest in additional research and development for similar cholestatic liver diseases, potentially expanding their portfolio and market share in the niche of rare liver disorders.
Lastly, the impact on Mirum Pharmaceuticals' stock could be significant, as groundbreaking treatment options like LIVMARLI® often lead to increased investor confidence and can drive stock prices upward. However, it is essential to consider the broader market context, including competitor activities and the overall performance of the biotech sector.
02/29/2024 - 08:30 AM
- Results demonstrate 70% risk reduction for long-term clinical outcomes in patients with Alagille syndrome (ALGS) treated with LIVMARLI (p<0.0001)
- Data are the first to demonstrate a six-year transplant-free survival benefit in patients with ALGS using a pharmacological interventional therapy
FOSTER CITY, Calif. --(BUSINESS WIRE)--
Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) today announced that Hepatology published an analysis demonstrating a statistically significant improvement in six-year event-free and transplant-free survival in patients with Alagille syndrome (ALGS) treated with LIVMARLI® (maralixibat) oral solution when compared with a natural history control group (p<0.0001). The analysis evaluated time to clinical outcome from the pooled LIVMARLI clinical studies versus a control cohort from the G Al A
“Patients with Alagille syndrome often undergo liver transplantation for complications related to cholestasis,” said Binita M. Kamath, MBBChir, Staff Physician and Senior Associate Scientist, The Hospital for Sick Children (SickKids), Toronto, Ontario, Canada , and senior author of the manuscript. “This seminal six-year analysis of LIVMARI versus a comparable natural history control group demonstrates a 70% risk reduction for clinical outcomes in patients treated with LIVMARLI.”
“We are grateful to the GALA Study Group for this important academic contribution and are thrilled about the recognition of this analysis by Hepatology ,” said Pam Vig, PhD, chief scientific officer and head of research at Mirum. “We would like to thank the patients who participated in the LIVMARLI studies as well as the Alagille Syndrome Alliance for their continued partnership and dedication to advancing research in this rare liver disease.”
The pre-specified statistical analysis was conducted independently by the lead author Dr. Bettina Hansen, Professor of Clinical Biostatistics at Erasmus MC, Netherlands and compared time to first clinical event in the LIVMARLI-treated patients with ALGS (n=84) versus a well-selected external natural history cohort treated with standard of care from the GALA database (n=469). Events were defined as liver transplantation, biliary diversion surgery, manifestations of portal hypertension, or death. The GALA control group was identified based on a pre-specified and blinded selection process to align with eligibility criteria from the LIVMARLI clinical studies. Multiple sensitivity and subgroup analyses were conducted to ensure statistical robustness of the primary result.
Data from the analysis demonstrated a significant improvement in six-year event-free survival with a p-value of <0.0001 (HR: 0.305, 95% CI: 0.189-0.491) translating to a 70% overall reduction for clinical outcomes with LIVMARLI. The analysis also showed statistically significant improvements in transplant-free survival (liver transplantation or death) as compared to the GALA cohort with a p-value of <0.0001 (after adjusting for age, sex, total bilirubin, and ALT) (HR: 0.332; 95% CI 0.197-0.559). Sensitivity and subgroup analyses demonstrated overall consistency with the primary results.
The full publication including additional data from the analysis is available on the Hepatology website.
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. In patients with ALGS, multiple organ systems may be affected by the mutation, including the liver, heart, kidneys, and central nervous system. 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. 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). 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.
About LIVMARLI® (maralixibat) oral solution
LIVMARLI® (maralixibat) oral solution is an orally administered, once-daily, ileal bile acid transporter (IBAT) inhibitor and the only approved medication 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. LIVMARLI is also approved by the European Commission for the treatment of cholestatic pruritus in patients with ALGS two months and older. For more information for U.S. residents, 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 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
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 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 cholestatic pruritus in patients with Alagille syndrome in the U.S. (three months and older), in Europe (two months and older), and in Canada . 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. Cholbam is FDA-approved for the treatment of bile acid synthesis disorders due to single enzyme defects 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, Chenodal, has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX, with positive topline results reported in 2023.
To learn more about Mirum, visit mirumpharma.com and follow Mirum on Facebook , LinkedIn , Instagram and Twitter .
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 potential for LIVMARLI to exceed real world outcomes of patients with ALGS and the clinical significance of reduction of serum bile acids on liver transplantation. 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.
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Source: Mirum Pharmaceuticals, Inc.
What is the significance of the results for patients with Alagille syndrome (ALGS) treated with LIVMARLI?
The results demonstrate a 70% risk reduction for long-term clinical outcomes and a six-year transplant-free survival benefit.
What is the comparison made in the analysis published by Hepatology?
The analysis compared six-year event-free and transplant-free survival in patients with ALGS treated with LIVMARLI to a natural history control group.
Who is the senior author of the manuscript mentioned in the PR?
Binita M. Kamath, MBBChir, Staff Physician and Senior Associate Scientist at The Hospital for Sick Children (SickKids), Toronto, Ontario, Canada.
What was the key finding of the analysis regarding clinical outcomes in patients with ALGS?
The analysis showed a 70% risk reduction for clinical outcomes in patients treated with LIVMARLI.
What is the ticker symbol for Mirum Pharmaceuticals, Inc.?
The ticker symbol is MIRM.
