- Late-breaking poster presentation features
LIVMARLI® data showing long-term maintenance of response in
patients with PFIC
- Four poster presentations highlight LIVMARLI
PFIC data as well as a poster with proof-of-concept trial data from
volixibat study in intrahepatic cholestasis of pregnancy
Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM) today announced new
data from its LIVMARLI and volixibat programs presented at The
Liver Meeting®, the American Association for the Study of Liver
Diseases (AASLD) annual meeting in Boston, Massachusetts.
Data were presented from the Phase 3 MARCH study and MARCH-ON
extension evaluating the efficacy and safety of LIVMARLI in
patients with progressive familial intrahepatic cholestasis (PFIC)
as well as the Phase 2 OHANA study evaluating the efficacy and
safety of volixibat in patients with intrahepatic cholestasis of
pregnancy (ICP).
MARCH was the largest and most genetically diverse trial of PFIC
to date, enrolling patients with deficiencies of BSEP, FIC1, MDR3,
TJP2, AND MYO5B, as well as those clinically diagnosed with PFIC
but without a known genetic variant.
“PFIC is a chronic, debilitating cholestatic liver disease
characterized by elevated bile acids and pruritus so severe that
patients can be listed for liver transplant even in the absence of
disease progression. We are excited to share the long-term benefits
observed across multiple measures including reductions in pruritus,
serum bile acids, improved liver health and growth for patients
with PFIC treated with maralixibat in multiple genetic types which
have not previously been reported,” said Pam Vig, PhD, head of
research and development at Mirum. “We are also pleased to share
the findings from the OHANA study of volixibat in patients with
ICP, showing a clear impact of volixibat on serum bile acids and
pruritus in this cholestatic setting.”
A summary of these data presented is featured below. Full
presentations can be found within the Publications and
Presentations section of Mirum’s website.
Late-breaker Poster
Presentation
Poster 5048-C: Long-term maintenance of response and improved
liver health with maralixibat in patients with progressive familial
intrahepatic cholestasis (PFIC): 2-year data from the MARCH-ON
study
The MARCH-ON extension study evaluated the long-term efficacy
and safety of maralixibat in patients with PFIC who received
maralixibat in the original MARCH study for 26 weeks and continued
for up to two years and those who were on placebo who went on to
receive maralixibat for up to one year. Significant and sustained
improvements in pruritus severity, serum bile acid (sBA) levels,
total bilirubin, and growth were observed with up to two years of
maralixibat treatment across the broadest range of genetic PFIC
types studied to date. The placebo-maralixibat group demonstrated
rapid (as early as three weeks) and significant improvements in
pruritus severity and sBA levels similar to those observed in the
original MARCH maralixibat group. No new safety signals were
observed. The most common treatment emergent adverse events were
GI, occurred early in treatment, and were mild and transient in
nature. These data suggest overall improved liver health with
maralixibat treatment in patients with PFIC that can be maintained
long-term.
Other Poster Presentations
Poster 4602-C: Improvements in pruritus with maralixibat are
associated with improved quality of life for patients with
progressive familial intrahepatic cholestasis: Data from the
MARCH-PFIC trial
Pruritus is known to be one of the most burdensome symptoms of
PFIC, occurring in the majority of patients and leading to sleep
disturbance, self-mutilation, and decreased school performance,
further contributing to impaired quality of life. An exploratory
endpoint in the MARCH study was to evaluate if a clinically
significant reduction in pruritus following treatment with
maralixibat was associated with an improvement in quality of life.
These data demonstrated that clinically significant reductions in
pruritus were associated with meaningful improvements in quality of
life, as evaluated across several domains. The maralixibat group
demonstrated significant differences between pruritus responders
and non-responders for PedsQL, PedsQL-SF, PedsQL-PF, and a trend
toward significance with FI-T. Clinically meaningful improvements
(MCID >4-5 points) across all HRQoL scales were experienced by
maralixibat responders. The placebo group showed no significant
differences between pruritus responders and non-responders in any
of the assessments. These data suggest that benefits of maralixibat
may extend beyond pruritus and yield meaningful improvements in
quality of life as well.
Poster 4604-C: Maralixibat leads to significant improvement
in cholestatic pruritus for children with progressive familial
intrahepatic cholestasis due to TJP2 or MYO5B deficiency: Data from
the MARCH-PFIC trial
The MARCH study assessed the broadest set of genetic types
associated with PFIC. The most common causes of PFIC are
deficiencies in BSEP (PFIC2), FIC 1, MDR3, TJP2, and MYO5B.
Patients with TJP2 deficiency have a predisposition to developing
hepatocellular carcinoma. The goal of this analysis was to
understand maralixibat’s potential to provide improvement across
key markers of the disease in patients with these two rare genetic
variants (TJP2, n=7, MYO5B, n=4). The results demonstrated that all
patients with either a TJP2 or MYO5B deficiency receiving
maralixibat achieved substantial improvements in pruritus and
reductions in sBA while patients who received placebo experienced
little benefit. Bilirubin levels were normalized in one participant
with MYO5B deficiency who received maralixibat. MARCH is the first
trial demonstrating benefit of IBAT inhibition for TJP2 and MYO5B
deficiencies and these data support the use of maralixibat in
patients with these genetic types.
Poster 4605-C: Maralixibat leads to significant improvements
in cholestatic pruritus for children with progressive familial
intrahepatic cholestasis without a genetic diagnosis: Data from the
MARCH-PFIC trial
The MARCH study evaluated patients (n=8) with a PFIC clinical
diagnosis without an identified genetic variant. The objective of
this analysis was to understand the efficacy and safety of
maralixibat treatment for patients clinically diagnosed with PFIC
but without a known genetic variant. Data demonstrated that
maralixibat was associated with improvements in pruritus, sBA
levels, total bilirubin, and direct bilirubin, as compared to
placebo. No new safety signals were observed. These data
demonstrate the utility of treating patients with PFIC but without
a known genetic variant with maralixibat.
Poster 4547-C: Efficacy, safety and tolerability of volixibat
in patients with intrahepatic cholestasis of pregnancy: A case
series of 4 patients
Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic
liver disease impacting pregnant woman. ICP is characterized by
elevated sBA and cholestatic pruritus, often impairing sleep and
quality of life. Elevated sBAs pose significant risk to the unborn
fetus. A Phase 2 open-label study, OHANA, was conducted with
volixibat, a minimally absorbed IBAT inhibitor, to evaluate the
efficacy and safety in four patients with ICP. Volixibat
demonstrated improvements in pruritus and sBA levels, signaling
proof of concept for volixibat in cholestatic disease. No
clinically meaningful changes in liver enzyme levels or hematology
parameters were observed after volixibat treatment. The most common
TEAEs were GI in nature, transient and moderate in severity.
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 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.
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 is currently being evaluated in late-stage clinical
studies in other rare cholestatic liver diseases including 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
is 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 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
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 three investigational
treatments for debilitating liver diseases. The LIVMARLI
development program includes the Phase 2b EMBARK study for biliary
atresia. Mirum’s second investigational IBAT inhibitor is
volixibat, which 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.
To learn more about Mirum, visit mirumpharma.com and follow
Mirum on Facebook, LinkedIn, Instagram and Twitter.
Forward-Looking Statements
This press release includes forward-looking statements
pertaining to the Company’s planned participation at a scientific
conference, including data presentation title and synopsis, which
may include discussion of the Company’s clinical and research data,
including the therapeutic potential and/or commercial viability of
our products and product candidates in various liver disease
indications. 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. The accuracy of such
statements is subject to a number of risks, uncertainties and
assumptions including, but are not limited to, the following
factors: the uncertainties inherent in research and development;
the uncertainties inherent in business and financial planning,
including, without limitation, risks related to Mirum’s business
and prospects, adverse developments in our focused markets, or
adverse developments in the U.S. or global regulatory environment
or economies generally; the continued impact of COVID-19 on our
business, operations and financial results; and competitive
developments. Other factors that might cause such a difference
include those discussed in the Company’s filings with the SEC. 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.
Abbreviations:
PedsQL-SF – Social functioning PedsQL-PF – Physical functioning
FI-T – Family Impact Total Scale HRQoL – Health Related Quality of
Life
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version on businesswire.com: https://www.businesswire.com/news/home/20231113329951/en/
Media: Erin Murphy 510-508-6521 media@mirumpharma.com
Investors: Andrew McKibben ir@mirumpharma.com
Sam Martin Argot Partners ir@mirumpharma.com
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