Edasalonexent, a potential oral therapy for Duchenne muscular dystrophy (DMD), can prevent the development of heart disease and help to preserve bone health, according to data from two studies in mouse models of DMD.
Catabasis Pharmaceuticals’ investigational treatment was also well-tolerated when given for up to 150 weeks (close to three years) to boys with DMD participating in the open-label extension part of the Phase 1/2 MoveDMD trial (NCT02439216), results presented at the Virtual 25th International Congress of the World Muscle Society showed.
Edasalonexent, formerly known as CAT-1004, is designed to inhibit the NF-κB pathway, a signaling pathway thought to be involved in muscle breakdown and the failure to repair damaged muscle tissue. By blocking this pathway, edasalonexent is expected to help preserve muscle health and slow DMD progression.
In one poster presented at the congress, “Inhibition of NF-κB signaling prevents the development of DMD-associated cardiomyopathy in mdx:Utrn+/- mice,” investigators at UT Southwestern working with Catabasis researchers showed that treatment with edasalonexent reduced heart enlargement and fibrosis (tissue scarring), helping preserve heart function in a mouse model of DMD.
In turn, the study, “Edasalonexent maintains bone density and bone strength in the mdx mouse model of Duchenne Muscular Dystrophy,” conducted by researchers at Shriners Hospital for Children and colleagues, showed that unlike the steroid prednisolone, treatment with edasalonexent did not negatively affect bone strength, density, or structure in a mouse model of DMD.
Investigators also demonstrated that in lab-cultured cells, edasalonexent blocked the NF-κB pathway and, unlike prednisolone, it did not activate the glucocorticoid receptor — the protein receptor that normally interacts with steroid hormones.
“As we approach top-line Phase 3 PolarisDMD results, which we expect to report in the fourth quarter of this year, we are pleased to share new findings from preclinical studies with edasalonexent that could support its potential as a foundational therapy for those affected by Duchenne,” Andrew Nichols, PhD, chief scientific officer of Catabasis, said in a press release.
“Cardiac function and bone health are critical components of Duchenne care and we are excited to learn more about these key areas that are important to patients, their caregivers and physicians,” Nichols added.
The company also presented new data from clinical trials assessing edasalonexent’s safety and efficacy in young boys.
In the poster “Edasalonexent Treatment in Young Boys with Duchenne Muscular Dystrophy Is Associated with Age-Normative Growth and Normal Adrenal Function,” Catabasis shared updated data from the open-label extension portion of the MoveDMD trial, assessing the safety, efficacy, and pharmacological properties of edasalonexent in boys, ages 4–8, with DMD.
Earlier trial data showed that after 72 weeks of treatment, edasalonexent was well-tolerated and helped to preserve muscle function and slow DMD progression in these patients.
New data showed that edasalonexent continued to be well-tolerated over up to 150 weeks. Diarrhea was the most common side effect observed, and was mild and temporary for most boys.
Study findings also indicated the experimental therapy did not interfere with boys’ normal growth, and had no impact on their bone health or adrenal function.
“Edasalonexent has the potential to be disease-modifying in DMD patients,” the researchers wrote.
MoveDMD’s results supported the launch of the one-year Phase 3 PolarisDMD (NCT03703882) trial, which is investigating the treatment’s safety and efficacy, against a placebo, in 131 Duchenne boys ages 4–7.
Boys completing PolarisDMD will have the chance to enroll in a 104-week, open-label extension study called GalaxyDMD (NCT03917719) to continue or begin treatment with edasalonexent. GalaxyDMD is also enrolling those who completed MoveDMD. Eligible siblings of main study patients may also be eligible for trial inclusion.
Catabasis also presented data from a baseline (study start) analysis of PolarisDMD, confirming the reliability of the North Star Ambulatory Assessment (NSAA) — a validated measure of motor function for Duchenne boys still able to walk independently — that will be used to assess the effects of treatment on motor function, the study’s primary goal.
The poster, “In the Global Phase 3 PolarisDMD Trial for Edasalonexent, Standardized Outcome Measure Training Produces Excellent Test-Retest Variability in the North Star Ambulatory Assessment,” showed similar NSAA scores during screening and again before boys started treatment, confirming that results are reproducible.
This analysis also confirmed the reliability of other tests being used to assess secondary study goals, including the 10-meter walk or run test, the four-stair climb speed test, and the time to stand speed test.
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