- Submission based on the positive Phase 3 RESTORE study
- Mirum holds orphan designation for chenodiol in CTX
- Potential to have first and only therapy indicated for CTX in
the US
Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) today announced the
submission of a new drug application (NDA) for chenodiol for the
treatment of patients in the U.S. with cerebrotendinous
xanthomatosis (CTX).
CTX is a rare autosomal genetic progressive disorder of
cholesterol metabolism that affects many parts of the body. In CTX,
a deficiency of the bile acid CDCA leads to a buildup of bile
alcohols which precedes a toxic accumulation of cholestanol.
Cholestanol is the key driver of symptomatic burden and disease
progression, including irreversible neurologic dysfunction. If not
treated, patients with CTX can experience symptoms that disrupt
their lives and can progress over time, including chronic diarrhea,
juvenile bilateral cataracts, tendon xanthomas, and neurologic
deterioration.
The submission of the NDA is based on the positive results of
the Phase 3 RESTORE study which evaluated chenodiol in adult
patients with CTX. The study met its primary endpoint of reduction
in bile alcohols with high statistical significance (p<0.0001).
The difference observed between placebo and active chenodiol at the
end of the randomized double-blind withdrawal period was 20-fold.
The RESTORE study also demonstrated that treatment with chenodiol
significantly improved serum cholestanol. The most common adverse
events were diarrhea and headache, the majority of which were mild
or moderate and not considered to be treatment related.
“Following the landmark RESTORE data, we are excited about the
potential to have an approved treatment option that may reduce the
progressive symptoms associated with this rare disease,” said Chris
Peetz, chief executive officer at Mirum. “If approved, chenodiol
would be the first and only medication approved to treat patients
with CTX, enabling earlier diagnosis and treatment of these
life-altering symptoms.”
“When you have CTX, timely diagnosis and treatment can have a
transformative impact on the lives of people living with this
disease,” said Jean Pickford, executive director, CTX Alliance. “We
were excited about the RESTORE data and are hopeful that the
chenodiol submission to the FDA will result in an approval,
enabling faster access to treatment and helping patients and their
families earlier in their disease journey.”
About the RESTORE Phase 3 Study
The Phase 3 RESTORE study was a randomized withdrawal,
placebo-controlled clinical trial which evaluated the safety and
efficacy of chenodiol in patients with cerebrotendinous
xanthomatosis (CTX). Chenodiol is administered at 250 mg three
times daily in tablet format. The objective of the RESTORE study is
to understand how the body responds, as measured by change in blood
and urine biomarkers associated with CTX, when treated with
chenodiol. The study involved a screening period (4 weeks), four
treatment periods (totaling 6 months), and a follow-up phone call
(30 days after last dose was administered). The four treatment
periods consisted of: an 8-week open-label chenodiol period, a
4-week randomized withdrawal period (placebo or chenodiol), a
second 8-week open-label chenodiol period for all patients, and a
second 4-week randomized withdrawal period (alternate treatment to
first withdrawal period).
The primary analysis assessed change at the end of each
double-blind withdrawal period. The study also included an
open-label pediatric treatment group where all patients received
liquid chenodiol. The study was conducted at multiple sites in the
United States and Brazil.
About Cerebrotendinous Xanthomatosis
Cerebrotendinous xanthomatosis (CTX) is a rare, progressive and
underdiagnosed disorder of cholesterol metabolism affecting many
parts of the body. In people with CTX, the body is unable to break
down cholesterol properly causing toxins (e.g., cholestanol and
bile alcohols) to build up throughout the body over time. The
disorder is inherited in an autosomal recessive genetic manner.
Signs and symptoms of CTX include neonatal cholestasis (jaundice or
bile flow interruption), chronic diarrhea, the development of
bilateral cataracts before the age of 18, development of tendon
xanthomas (fatty deposits in the tendons) during teenage years or
later, and neurologic deterioration. The types, combinations and
severity of symptoms can be different from person to person making
diagnosis challenging and often delayed.
About chenodiol tablets
Chenodiol tablets is another name for chenodeoxycholic acid
(CDCA). CDCA is a naturally occurring bile acid that was originally
approved for the treatment of people with radiolucent stones in the
gallbladder. More recently, the US Food and Drug Administration
(FDA) granted chenodiol orphan drug designation for
cerebrotendinous xanthomatosis (CTX). CTX is a rare progressive
disorder that can affect the brain, spinal cord, tendons, eyes and
arteries. Chenodiol is not yet indicated for the treatment of CTX
but has received a medical necessity determination in the U.S. by
the FDA.
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)
three months of age and older and for progressive familial
intrahepatic cholestasis (PFIC) five years 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.
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
Limitation of Use: LIVMARLI is not for use in PFIC type 2
patients who have a severe defect in the bile salt export pump
(BSEP) protein.
LIVMARLI can cause side effects, including:
Liver injury. Changes in certain liver tests are common
in patients with Alagille syndrome and PFIC but can worsen during
treatment. These changes may be a sign of liver injury. In PFIC,
this can be serious or may lead to liver transplant or death. Your
healthcare provider should do blood tests and physical exams 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), bloating in your
stomach area, loss of appetite or bleeding or bruising more easily
than normal.
Stomach and intestinal (gastrointestinal) problems.
LIVMARLI can cause stomach and intestinal problems, including
diarrhea and stomach pain. Your healthcare provider may advise you
to monitor for new or worsening stomach problems including stomach
pain, diarrhea, blood in your stool or vomiting. 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 is common in patients with Alagille syndrome and
PFIC but may worsen during treatment. Your healthcare provider
should do blood tests before starting and during treatment and may
monitor for bone fractures and bleeding which have been reported as
common side effects.
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
two rare liver diseases affecting children and adults. It 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 other regions globally. It is also
approved in the U.S. in cholestatic pruritus in PFIC patients five
years of age and older. CHOLBAM is FDA-approved for the treatment
of bile acid synthesis disorders due to single enzyme deficiencies
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 (X).
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 benefits of Chenodiol
tablets for patients with CTX, the success of any planned
regulatory submissions relating to CTX and, if approved, the real
world impact of Chenodiol versus the results seen in the RESTORE
clinical trial. 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. A further
description of risks and uncertainties can be found in Mirum’s
Annual Report on Form 10-K for the fiscal year ended December 31,
2023 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned “Risk Factors,” as well as in its
subsequent reports on Form 8-K, all of which are filed with the
U.S. Securities and Exchange Commission and available at
www.sec.gov.
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version on businesswire.com: https://www.businesswire.com/news/home/20240628738394/en/
Media Contact: Erin Murphy media@mirumpharma.com
Investor Contact: Andrew McKibben investors@mirumphama.com
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