– 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) | P-value | |
| Primary Endpoint | ||
| Urine 23S-Pentol (bile alcohol) ng/mL | 20-fold increase (CI: 10.3, 43.5) | <0.0001 |
| Key Secondary Endpoints | ||
| Rescue medication* | 61.5% of placebo patients (CI: 31.6%, 86.1%) | 0.0006 |
| Plasma cholestanol µg/mL | 2.8-fold increase (CI: 1.5, 5.2) | 0.0083 |
| Plasma 7αC4 ng/mL | 50-fold increase (CI: 25.0, 66.7) | <0.0001 |
| * 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.
