Results of the phase 2 MoveDMD trial of edasalonexant suggest the investigational Duchenne muscular dystrophy (DMD) agent is well-tolerated, in addition to being associated with positive growth patterns without any indications of negative effects on bone health or adrenal function.
The investigators noted that with this lack of adverse effects, which are often associated with high-dose steroid treatment, edasalonexant holds promise as a disease-modifying treatment for patients with DMD. Additionally, they note that the study design supports the ongoing, 8-site, phase 3 PolarisDMD (NCT03703882) clinical trial.
The data on Catabasis’s oral small molecule NF-kB inhibitor were presented virtually by Erika Finanger, MD, in light of the cancellation of the on-site portion of the 2020 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference. All told, the study included 31 steroid-naïve boys. Those treated with 100 mg/kg edasalonexant experienced improvements in North Star Ambulatory Assessment (NSAA) scores, 4-Stair Climb scores, 10-Meter Walk/Run assessments, and Time to Stand assessments.
“During the off-treatment control period, we saw a functional decline in all 4 of the measures, including the NSAA, as would be expected for natural history,” Finanger, an assistant professor of pediatrics, division of neurology, Oregon Health and Sciences University School of Medicine, said. “With treatment with edasalonexant at the 100 mg/kg dose, which is the dose being used in the phase 3 trial, we see a slowing of this disease progression in all 4 of the measures. Change in decline occurred early—as early as 12 weeks—and persisted over the 72 weeks of therapy.”
A composite magnetic resonance imaging (MRI) T2 measure was utilized as a biomarker of disease progression during the trial period. Although it was not statistically significant, 12-week measures showed a directionally positive change among boys in the treatment group compared to the placebo group.
Notably, edasalonexant’s availability as an orally administered soft-gel capsule—in 2 doses, 100 mg or 250 mg—did not appear to trouble the young cohort of patients. The majority (97%) of those screened for the trial were able to swallow capsules, with only a single patient failing screening due to an inability to do so, according to Finanger.
“The sites were very successful in teaching those boys who did not already have this skill,” Finanger explained. “In addition, for boys who were able to swallow the smaller size, the majority were able to transition to the larger sized capsules by mid-way through the study. Overall, compliance with the study medication was very high.”
Of the 31 enrolled patients, 24 (77%) began on the 100 mg capsule, with most transitioned to the 250 mg capsule by Week 24. Compliance with the medication was reported at roughly 98%.
The height of boys in the cohort increased along an expected growth curve for unaffected individuals, with a reported increase of 1.9 inches per year. As well, weight increases were 4.5 lbs per year, less than the mean for unaffected boys, which resulted in normalized body mass index (BMI) measurements, in opposition to a typical elevated BMI associated with natural history in boys with DMD.
There was no evidence of adrenal insufficiency, with no reported clinically significant changes in either cortisol or adrenocorticotropic hormone (ACTH). In over 60 patient-years of exposure, only 2 fractures were reported—radius and metatarsal—with no minimal trauma. As for safety, the most common treatment-related adverse event (AE) was diarrhea, which was deemed generally mild and transient. There were no serious AEs reported.
The FDA previously granted orphan drug, fast track, and rare pediatric disease designations to edasalonexent. PolarisDMD, which is fully enrolled with boys with DMD aged 4 to 7 who have not been treated with steroids for ≥6 months, is randomizing patients 2:1 to receive either edasalonexent (100 mg/kg capsule) or placebo, with clinic visits every 3 months. The primary end point is the change in NSAA scores at 1 year. Top-line results are expected to be reported in the fourth quarter of 2020. Catabasis is anticipating utilizing that study data to support a new drug application filing with the FDA in 2021.
Finkel R, Finanger E, Tennekoon G, et al. Edasalonexant Treatment in Young Boys With Duchenne Muscular Dystrophy Is Associated With Age-Normative Growth and Normal Adrenal Function. Presented at: 2020 MDA Clinical & Scientific Conference; March 24, 2020. Poster 60.