Phase 2 study results of edasalonexent, an investigational oral small molecule NF-kB inhibitor for the treatment of Duchenne muscular dystrophy (DMD), suggest that the therapy is associated with slowed disease progression, as well as a good safety profile over the course of more than 50 patient-years of exposure in boys with the disease.1
Treatment with the drug, assessed at a dose of 100 mg/kg per day in the MoveDMD trial, ultimately demonstrated improvements in the 10-meter walk/run scores, time-to-stand scores, and 4-stair climb scores in 31 steroid-naïve boys with DMD aged 4 to 7. In addition to functional measures, MRI assessments of muscle integrity were compared to the off-treatment control period.
These data were presented by principal investigator Richard Finkel, MD, chief of neurology, department of pediatrics, at Nemours Children’s Health System, at the 24th International Annual Congress of the World Muscle Society, in Copenhagen, Denmark.2
“Our goal is to provide a therapy for DMD that slows disease progression, has a compelling safety profile and can be used in boys regardless of mutation,” Joanne Donovan, MD, PhD, chief medical officer, Catabasis, said in a statement. “The safety and tolerability data from the MoveDMD trial support the potential of edasalonexent to become a foundational therapy for those with Duchenne, from the time of diagnosis onwards.”
Safety measures in MoveDMD included assessments of growth and adrenal function, measured with ACTH and cortisol. The therapy was deemed well-tolerated, including in 2 patients who were eligible for eteplirsen and in whom eteplirsen was initiated. No negative trends in cortisol or ACTH were observed with edasalonexent. Over the more than 55 cumulative patient-years of exposure, the majority of adverse events (AEs) were considered mild, with the most common treatment-related AE being mild and transient diarrhea. No serious AEs were observed.
Notably, body mass index (BMI) was initially elevated into the 70th percentile of expected BMI for unaffected boys, though it decreased to the 55th percentile with treatment. This, the company noted, is reflective of the maintenance of height percentile while weight percentile decreased. Heart rate declined toward age-normative values.
“Edasalonexent has broad potential for benefit and can be used as a monotherapy as well as potentially with other therapies. Our hope is to improve the quality of life for those affected by Duchenne,” Donovan said.
The FDA has previously granted orphan drug, fast track, and rare pediatric disease designations to edasalonexent. The treatment is currently being assessed in the phase 3 PolarisDMD study (NCT03703882), which has a target enrollment of 125 boys with DMD aged 4 to 7 who have not been treated with steroids for ≥6 months. Patients will be randomized 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 North Star Ambulatory Assessment scores at 1 year.
Top-line results of PolarisDMD 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.
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1. Catabasis Pharmaceuticals Presents Edasalonexent, a Potential Foundational Treatment for Duchenne Muscular Dystrophy [press release]. Cambridge, MA: Catabasis; Published October 5, 2019. businesswire.com/news/home/20191005005004/en. Accessed October 7, 2019. 2. Finkel R, Vandenborne K, Sweeney H, et al. Treatment of young boys with Duchenne muscular dystrophy with the NF- κB inhibitor edasalonexent showed a slowing of disease progression as assessed by MRI and functional measures. Presented at: World Muscle Society annual meeting; October 1-5, 2019; Copenhagen, Denmark. Abstract O.42.