Catabasis Pharmaceuticals and the Jain Foundation have started a preclinical research collaboration to study edasalonexent as an oral treatment candidate for dysferlinopathy, a group of muscle diseases that includes limb-girdle muscular dystrophy (LGMD) type 2B.
Edasalonexent, formerly CAT-1004, is a small molecule designed to block the NF-kB cell signaling route — a potential driver of muscle dystrophy, with a key role in skeletal and cardiac muscle breakdown. Through this mechanism, edasalonexent is thought to help preserve muscle function and slow disease progression. The experimental therapy is currently in Phase 3 clinical testing in boys with Duchenne muscular dystrophy (DMD).
Dysferlinopathy, which also includes Miyoshi myopathy, is a group of rare muscle disorders characterized by slowly progressive muscle weakness and wasting. The disorders are caused by mutations in the gene DYSF, which provides instructions for making dysferlin, a protein that normally works to provide structure to muscle fibers, and protect them.
In people with dysferlinopathy, muscles lack that key dysferlin protein, which results in chronic activation of the NF-kappa B pathway, muscle fiber damage, and failure to repair injured fibers.
Through the collaboration of Catabasis with the Jain Foundation, a non-profit dedicated to finding a cure for muscular dystrophy caused by dysferlin deficiency, researchers will conduct a preclinical study to evaluate the therapeutic potential of edasalonexent in dysferlinopathy.
The study will measure disease progression in dysferlin-deficient mice treated with edasalonexent, and use magnetic resonance imaging (MRI) and magnetic resonance spectroscopy to assess muscle volume, fat accumulation, and other changes. The initial results are expected in the first half of 2020.
“We look forward to working with Catabasis to advance research for Dysferlinopathy,” Laura Rufibach, PhD, and Doug Albrecht, PhD, co-presidents of the Jain Foundation, said in a press release.
“Patients with dysferlinopathy (LGMD2B / Miyoshi myopathy) experience a progressive and debilitating decline in muscle function which significantly impacts their lives,” Rufibach and Albrecht said. “We are excited to explore the potential of edasalonexent to benefit those living with this disease.”
In Duchenne research, results of the MoveDMD Phase 1/2 trial and its open-label extension (NCT02439216) showed that treating boys ages 4-7 with edasalonexent slowed disease progression and preserved muscle function compared with an off-treatment period. Biomarkers of muscle health and inflammation also showed significant improvements.
Evidence of NF-kB activation in both dysferlinopathy and DMD “suggests a similar disease mechanism and opportunity for intervention,” said Andrew Nichols, PhD, Catabasis’ chief scientific officer.
“Through this collaboration, we look forward to learning more about the potential of edasalonexent in dysferlinopathy,” he added.
The treatment’s efficiency and safety are being evaluated in children with Duchenne in the Phase 3 trial PolarisDMD (NCT03703882). Enrollment was just completed and exceeded the target number of participants, Catabis said. A total of 130 boys, ages 4 to 7, with any mutation type, have been enrolled in the U.S., Canada, Europe, Israel, and Australia.
“We are thrilled to reach this important milestone. The interest and feedback from families and trial sites has been overwhelmingly positive,” Joanne Donovan, MD, PhD, Catabasis’ chief medical officer, said in another press release.
“Edasalonexent has the potential to be a foundational therapy, providing benefit to boys, regardless of their underlying mutation, with the potential to benefit muscle function, as well as cardiac function and bone health,” she added.
Participants in PolarisDMD will be randomly assigned to receive either edasalonexent capsules three times per day (dose of 100 mg per kg per day) or a placebo, for 52 weeks, after which all boys and their eligible siblings may continue through an open-label extension study called GalaxyDMD.
Top-line results from PolarisDMD are expected in the fourth quarter of 2020. The findings are anticipated to support a New Drug Application filing with the U.S. Food and Drug Administration in 2021.
“We look forward to completing the trial next year and are working diligently toward the goal of making edasalonexent available to patients,” Donovan said.