Mirum Pharmaceuticals Announces Positive Phase 3 RESTORE Study Results Evaluating Chenodal in Patients with Cerebrotendinous Xanthomatosis

Oct 2, 2023

- Primary endpoint met (p<0.0001); 20-fold difference in urine bile alcohols

- First and only prospective, controlled clinical trial in CTX

- Plasma cholestanol endpoint met (p=0.0083), the driver of poor outcomes in CTX patients

- Data to be submitted for presentation at future medical congress

- Mirum plans to file an NDA with the U.S. FDA in the first half of 2024

Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM) today announced positive data from the Phase 3 RESTORE study evaluating Chenodal® (chenodiol) tablets in 13 adult patients with cerebrotendinous xanthomatosis, or CTX. The study objective was to evaluate the safety and efficacy of Chenodal by measurement of urine bile alcohols and other secondary measures. The primary endpoint of reduction in bile alcohols (urine 23S-pentol) was highly statistically significant (p<0.0001). The difference between placebo and active Chenodal at the end of the randomized double-blind withdrawal period was 20-fold.

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. Results from the RESTORE study demonstrated that treatment with Chenodal not only improved urine bile alcohols but also serum cholestanol. Additionally, a greater proportion of patients receiving placebo required blinded rescue therapy, demonstrating the robustness of the effect.

“The statistically significant reductions in bile alcohols and cholestanol underscore the potential for Chenodal to have a dramatic and meaningful impact on patients with CTX,” said Chris Peetz, president and chief executive officer at Mirum. “This is an extraordinary outcome, and we look forward to moving quickly to submit these data to the FDA with the goal of broadening the impact of Chenodal for patients with CTX. We are grateful to the patients and healthcare providers who made these results possible, and to the Travere team for their dedicated work leading this landmark study.”


Difference at end of double-blind period (placebo relative to Chenodal)


Primary Endpoint



Urine 23S-Pentol (bile alcohol) ng/mL

20-fold increase (CI: 10.3, 43.5)


Key Secondary Endpoints



Rescue medication*

61.5% of placebo patients (CI: 31.6%, 86.1%)


Plasma cholestanol µg/mL

2.8-fold increase (CI: 1.5, 5.2)


Plasma 7αC4 ng/mL

50-fold increase (CI: 25.0, 66.7)


* Proportion of patients on placebo requiring rescue Chenodal during double-blind withdrawal periods

The most commonly reported adverse events while on Chenodal were diarrhea (n=5) and headache (n=3). The majority of adverse events reported were mild or moderate in severity and not considered to be treatment-related.

“Because the diagnostic odyssey for CTX is typically long and arduous and the complications serious, it is critical that patients are treated quickly following diagnosis to ameliorate or prevent symptoms that can severely impact their lives,” said Robert Steiner, MD, professor, geneticist, and CTX Alliance medical and scientific advisory board member. “These data demonstrate a strong potential to help patients avoid the devastating effects of CTX.”

“CTX is a rare multi-symptom disease that affects each patient very differently, and can significantly impact a person’s quality of life,” said Jean Pickford, executive director, CTX Alliance. “For many patients and their families, the diagnostic journey is challenging and navigating the symptoms is ongoing. Once diagnosed, patients and their families are thrust into the world of a rare disease that can feel isolating and overwhelming. However, we are thrilled to see these impressive data from the RESTORE study. A change in bile alcohols and cholestanol have the potential to reduce the progressive symptoms associated with this rare disease.”

Data from the RESTORE study will be presented at an upcoming scientific congress, including forthcoming results from the open-label pediatric group of patients. In addition, Mirum will be submitting a new drug application to the U.S. FDA in the first half of 2024.

About the RESTORE Phase 3 Study

The Phase 3 RESTORE study is a randomized withdrawal, placebo-controlled clinical trial which evaluated the safety and efficacy of Chenodal in patients with cerebrotendinous xanthomatosis (CTX). Chenodal 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 Chenodal. 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 Chenodal period, a 4-week randomized withdrawal period (placebo or Chenodal), a second 8-week open-label Chenodal 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 Chenodal.

The study was conducted at multiple sites in the United States and Brazil.

About Cerebrotendinous Xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is an autosomal, recessive, progressive genetic disorder resulting from a deficiency of a key enzyme in the bile acid synthesis pathway. CTX is characterized by fatty yellow nodules (xanthomas) located in the connective tissues within the brain. These deposits can cause progressive damage to the brain and other areas of the body. As the clinical course progresses, irreversible neurological deterioration leads to premature death. CTX is a rare disease affecting one to two thousand people in the United States.

About CHENODAL® (chenodiol) tablets

Chenodiol 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 Chenodal orphan drug designation for cerebrotendinous xanthomatosis (CTX). CTX is a rare progressive disorder that can affect the brain, spinal cord, tendons, eyes and arteries. Chenodal is not indicated for the treatment of CTX but has received a medical necessity determination in the U.S. by the FDA. Full data from the Phase 3 RESTORE clinical trial are expected to be presented at an upcoming medical congress.

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 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 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 contains “forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Such forward-looking statements, including those regarding the clinical potential and regulatory process for Chenodal, the data resulting from the RESTORE trial, and the development success of Mirum products and candidates involve risks and uncertainties. The Company’s experience and results may differ materially from the experience and results anticipated in such 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.

Erin Murphy

Andrew McKibben

Sam Martin
Argot Partners

Source: Mirum Pharmaceuticals, Inc.