- Results demonstrate statistically significant
improvement in six-year event-free survival (p<0.0001) and
transplant-free survival (p<0.0001)
- Study presented by Global Alagille Alliance
(GALA) at The Liver Meeting® (AASLD) in a late-breaking oral
presentation; selected to be featured in Best of Liver Meeting
series
- Data underscore LIVMARLI’s potential to delay
liver transplant and improve disease outcomes associated with
Alagille syndrome
Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) today announced that
a new analysis comparing pooled LIVMARLI™ (maralixibat) oral
solution clinical trial data with a natural history cohort was
presented at the American Association for the Study of Liver
Diseases annual congress, The Liver Meeting®. LIVMARLI is an oral
ileal bile acid transporter (IBAT) inhibitor recently 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.
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the full release here:
https://www.businesswire.com/news/home/20211115006047/en/
Significant Improvement in Event-Free
Survival in Patients with ALGS with LIVMARLI Compared to Untreated
Cohort (Graphic: Business Wire)
The oral, late-breaking session, which was selected as part of
the “Best of the Liver Meeting” series, reported on an analysis
independently conducted and presented by Dr. Bettina Hansen on
behalf of Dr. Binita Kamath and the Global Alagille Alliance (GALA)
Study Group, which has aggregated the largest global natural
history clinical database established for ALGS. The analysis
evaluated six years of follow-up from pooled LIVMARLI studies
(n=84) in ALGS and compared it against an external natural history
control cohort from the GALA database. The objective of the
analysis was to compare the time to first clinical event in
LIVMARLI-treated patients with ALGS versus a natural history
cohort, with events defined as liver transplantation, biliary
diversion surgery, decompensation events (ascites requiring therapy
or variceal bleeding), or death. Additional analyses included
transplant-free survival as well as several sensitivity and
subgroup analyses to ensure robustness of the findings. The GALA
control group was selected based on alignment with eligibility
criteria from the LIVMARLI clinical studies.
The analysis demonstrated a highly 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
with a p-value of <0.0001 (HR: 0.332, 95% CI: 0.197-0.559).
These data underscore LIVMARLI’s potential to have long-term and
sustained impact for patients with ALGS.
“The extensive real-world analysis conducted by GALA validates
the statistical robustness of the findings and suggest that
patients who are treated with LIVMARLI may experience statistically
significant event-free survival and transplant-free survival versus
the natural history cohort,” said Bettina Hansen, Ph.D., Associate
Professor of Biostatistics at the Toronto Centre for Liver Disease,
Toronto General Hospital, Toronto General Hospital & University
of Toronto, Canada, on behalf of the GALA Study Group.
“Cholestatic pruritus associated with Alagille syndrome has a
dramatic and debilitating impact on the lives of patients and is a
leading indication for liver transplantation,” said Pam Vig, Ph.D.,
Chief Scientific Officer and Head of R&D at Mirum. “The
six-year analysis demonstrates that LIVMARLI significantly improves
event-free survival and transplant-free survival, further
supporting the impact of LIVMARLI in this patient population.”
Also at the meeting, a second late-breaker presentation was
given by Dr. Ron Sokol. These complementary data analyzed
predictors of event-free survival and transplant-free survival in
76 patients treated with LIVMARLI. Variables that were predictive
of event-free survival included specific thresholds of week 48
total bilirubin, and week 48 serum bile acids. Change in baseline
to week 48 in pruritus was also predictive of event-free survival
and transplant-free survival. Sixty out of 76 patients remained
event-free at the time of analysis, with up to six years of
treatment with LIVMARLI. These data highlighted potential
prognostic markers that could help to inform medical management for
patients receiving LIVMARLI treatment.
To learn more about the data presented during the meeting,
please visit the Alagille syndrome section of our Publications
& Presentations page on Mirum’s website.
The results of the natural history comparison analysis were
included in Mirum’s recent marketing authorization application
submission (MAA) to the European Medicines Agency (EMA) for
LIVMARLI in the treatment of cholestatic liver disease in patients
with ALGS. The MAA is currently under review and Mirum is preparing
for a launch of LIVMARLI in Europe in the second half of 2022, if
approved by the EMA.
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 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 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.
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
IMPORTANT SAFETY INFORMATION
LIVMARLI can cause serious 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 the Global Alagille Alliance (GALA)
Launched in October 2017, the Global ALagille
Alliance (GALA) Study is advancing research and
changing lives. By pooling together medical records from around the
world to create a vast one-stop database of patient information,
this three-year effort will be the bedrock of future research
projects that will unravel the mysteries of Alagille Syndrome
(ALGS). The cornerstone of this effort is a comprehensive medical
record review of patients with ALGS up to 30 years of age from 1997
to present. GALA’s overarching aim is to conduct a comprehensive
analysis of an international group of individuals with ALGS which
will increase understanding of the disease and identify the
challenges and needs of this unique population.
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 one year of
age and older.
Mirum’s late-stage pipeline includes two investigational
treatments for debilitating liver diseases affecting children and
adults. Maralixibat (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 study
for progressive familial intrahepatic cholestasis (PFIC) and the
EMBARK Phase 2b study for patients with biliary atresia. In
addition, Mirum has an expanded access program open in Canada,
Australia, the UK and several countries in Europe for eligible
patients with Alagille syndrome.
Mirum has submitted a Marketing Authorization Application to the
European Medicines Agency for LIVMARLI for the treatment of
cholestatic liver disease in patients with Alagille syndrome.
Mirum’s second investigational treatment, volixibat, also an
oral IBAT inhibitor, is being evaluated in two registrational
studies including the OHANA Phase 2b study for pregnant women with
intrahepatic cholestasis of pregnancy and the VISTAS Phase 2b study
for adults with primary sclerosing cholangitis. Mirum is planning
to launch a Phase 2b study in primary biliary cholangitis later
this year.
To augment its pipeline in cholestatic liver disease, Mirum has
acquired the exclusive option to develop and commercialize gene
therapy programs VTX-803 and VTX-802 for PFIC3 and PFIC2,
respectively, from Vivet Therapeutics SAS, following preclinical
evaluation and investigational new drug-enabling studies.
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Forward-Looking Statements
This press release includes forward-looking statements
pertaining to the Company’s planned participation at a scientific
conference, which may include discussion of the Company’s product
candidates and technologies, and the therapeutic potential thereof.
Such forward-looking statements are subject to risks and
uncertainties that could cause actual results to differ materially
from those expressed or implied in such statements. Applicable
risks and uncertainties include those relating to our preclinical
research and clinical programs and other risks identified under the
heading “Risk Factors” included in our most recent Form 10-Q and
Form 10-K filings and in other future filings with the SEC. The
forward-looking statements contained in this press release reflect
Mirum's current views with respect to future events, and Mirum does
not undertake and specifically disclaims any obligation to update
any forward-looking statements.
The Liver Meeting® is a registered trademark of the American
Association for the Study of Liver Diseases.
1Danks, et al. Archives of Disease in Childhood 1977 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
View source
version on businesswire.com: https://www.businesswire.com/news/home/20211115006047/en/
Media: Erin Murphy media@mirumpharma.com
Investors: Ian Clements, Ph.D. ir@mirumpharma.com
Sam Martin Argot Partners ir@mirumpharma.com
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