Catabasis Pharmaceuticals’ investigational oral therapy edasalonexent failed to preserve muscle function and overall functionality in boys with Duchenne muscular dystrophy (DMD), top-line data from the PolarisDMD Phase 3 clinical trial show.
“We are deeply saddened and disappointed by the results of our Phase 3 PolarisDMD trial,” Jill C. Milne, PhD, Catabasis’ CEO, said in a press release.
Based on the results, the company decided to discontinue the clinical development of edasalonexent.
“I want to sincerely thank all of the boys, their families and caregivers, investigators and the trial sites that participated in and enabled this program,” Milne said, adding that “the entire Catabasis team has worked tirelessly to find a treatment for this progressive disease.”
The company also will stop GalaxyDMD (NCT03917719), the extension study designed to assess edasalonexent’s long-term safety and effectiveness in DMD patients who completed other trials of the therapy, including PolarisDMD (NCT03703882), as well as in eligible siblings.
In a recent webinar hosted by Parent Project Muscular Dystrophy (PPMD), Joanne M. Donovan, MD, PhD, Catabasis’ chief medical officer, said that participants in GalaxyDMD and PolarisDMD can contact the principal investigator at their clinical site for more information.
PolarisDMD’s full data is expected to be presented at an upcoming scientific conference and submitted for publication in a peer-reviewed journal.
“We hope that our data and work to date can be used to benefit ongoing and future research in DMD,” Milne said.
Edasalonexent, formerly known as CAT-1004, is a small molecule designed to block the NF-kappa B pathway, a signaling route involved in muscle breakdown and the failure to repair damaged muscle tissue. By blocking this pathway, edasalonexent was expected to help preserve muscle health and slow DMD progression.
These results supported the launch of the one-year PolarisDMD study, which evaluated edasalonexent’s in 131 boys ages 4–7 with DMD, regardless of mutation type, and who had not been on steroids for at least six months prior to enrollment. Boys on a stable dose of Exondys 51 (eteplirsen) also were eligible to enroll.
Participants, recruited at 37 clinical sites across eight countries, were assigned randomly to receive three capsules a day of either edasalonexent (100 mg/kg per day) or a placebo for one year.
PolarisDMD’s main goal was to assess changes in motor and functional abilities — measured by the North Star Ambulatory Assessment score — after one year of treatment with edasalonexent, compared with a placebo.
Secondary goals included safety measures and changes in timed function tests, adapted to age — including time to stand, 4-stair climb, and 10-meter walk or run tests. The levels of muscle enzymes, bone and heart health, as well as parent-reported outcomes, also were assessed.
Results showed that edasalonexent was not superior to placebo in preserving motor and functional abilities. Also, while boys receiving edasalonexent were faster in the timed tests than those on a placebo, these differences did not reach statistical significance.
In the webinar, Donovan also said that differences between groups in timed tests were even greater when looking only at the younger boys (4 and 5 years old), but this potential benefit was not strong enough to move forward.
Taken together, these findings showed that the trial failed to meet both its main and secondary effectiveness goals.
In addition, no significant improvements were seen with edasalonexent in muscle enzyme levels, heart rate, and parent-reported outcomes. Additional bone and heart data are still being analyzed, and Catabasis will share them with the Duchenne community as they become available.
The therapy was generally safe and well-tolerated, with most adverse side effects being mild, consistent with the safety profile reported in previous trials. The most common side effects were diarrhea, vomiting, abdominal pain, and rash. No treatment-related serious side effects or reductions in therapy dose were reported.
According to information shared in the webinar, 93% of the boys completing PolarisDMD chose to enter the GalaxyDMD extension study, in which all would receive the therapy for two years.
Catabasis said that the COVID-19 pandemic had no meaningful impact on the trial or its results.
“These results are disheartening for the Duchenne community, and specifically for the boys who participated in this trial and their families,” said Pat Furlong, PPMD’s founding president and CEO.
However, they contribute to “the natural history data of Duchenne,” she added, and “to the knowledge base that will one day produce a foundational, long-term therapy for this disease.”
“The continued advancement of research and the development of possible treatment options will remain of critical importance to our community. We appreciate Catabasis’ efforts and commitment to every family that is or has ever been affected by Duchenne,” Furlong said.
Catabasis plans to work with external advisors to explore and evaluate strategic options going forward.
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