Mirum Submits New Drug Application to FDA for Chenodiol for the Treatment of CTX
- 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
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
“When you have CTX, timely diagnosis and treatment can have a transformative impact on the lives of people living with this disease,” said
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
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
About LIVMARLI® (maralixibat) oral solution
LIVMARLI® (maralixibat) oral solution is an orally administered, once-daily, ileal bile acid transporter (IBAT) inhibitor approved by the
LIVMARLI is also the only approved IBAT inhibitor approved by the
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
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
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
View source version on businesswire.com: https://www.businesswire.com/news/home/20240628738394/en/
Media Contact:
media@mirumpharma.com
Investor Contact:
investors@mirumphama.com
Source: