- 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
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 Global
Alagille Alliance (GALA) clinical database, the largest
global ALGS natural history database.
“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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240229510785/en/
Media Contact: Erin Murphy media@mirumpharma.com
Investor Contacts: Andrew McKibben ir@mirumpharma.com
Sam Martin Argot Partners ir@mirumpharma.com
Mirum Pharmaceuticals (NASDAQ:MIRM)
Historical Stock Chart
From Apr 2024 to May 2024
Mirum Pharmaceuticals (NASDAQ:MIRM)
Historical Stock Chart
From May 2023 to May 2024