Mirum Reports Positive Phase 3 Study Results Evaluating Chenodal in Patients with CTX

Rare Daily Staff

Mirum Pharmaceuticals reported positive data from the phase 3 RESTORE study evaluating Chenodal tablets in 13 adult patients with 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.

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. The difference between placebo and active Chenodal at the end of the randomized double-blind withdrawal period was 20-fold.

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 CEO 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.”

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.

“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. Food and Drug Administration in the first half of 2024.

The phase 3 RESTORE study is a randomized withdrawal, placebo-controlled clinical trial which evaluated the safety and efficacy of Chenodal in patients with 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.

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.

Photo: Jean Pickford, executive director, CTX Alliance