The soon-to-open PolarisDMD trial is a global and one-year, placebo-controlled study that will assess the safety and efficacy of edasalonexent in boys, ages 4 through 7, with DMD. The collected data is expected to support requests for its approval as a Duchenne treatment. [Editor’s note: PolarisDMD (NCT03703882) opened on Oct. 2, and patient recruitment is beginning. More information is available here.]
Top-line results from the trial are anticipated in the second quarter of 2020.
“We are very excited to initiate our Phase 3 PolarisDMD trial as we believe edasalonexent has tremendous potential to become the new standard of care for all affected by Duchenne, regardless of mutation type and from the time of diagnosis throughout their lifespan,” Joanne Donovan, MD, PhD, chief medical officer of Catabasis, said in a press release.
Edasalonexent (formerly known as CAT-1004), is a potential disease-modifying therapy specifically designed to have a broader effect than DMD mutation-specific mechanisms, which might only treat subsets of patients. It inhibits a protein called NF-kB — a key link between loss of dystrophin and disease development — with a major role in the initiation and progression of skeletal and cardiac muscle disease in DMD.
Approximately 40 clinical sites across the United States, Australia, Canada, Europe, and Israel are expected to participate in the new study. Trial sites across the United States are going to start enrolling eligible patients in the upcoming days, the company said in its release, and continue to do so into next year. International sites are expected to open in early 2019.
PolarisDMD plans to enroll 125 DMD boys, regardless of their genetic mutation, who are not being treated with steroids for at least six months prior the trial’s initiation. Boys currently taking a stable dose of Exondys 51 (eteplirsen) may be eligible to participate.
Patients will be randomized in a 2:1 ratio to receive 100 mg/kg per day of oral edasalonexent or a placebo for one year. After this, those who complete the study will have the opportunity to move into an open-label extension trial and either continue or start treatment with edasalonexent.
Researchers will evaluate the therapy’s impact on the children’s ability to walk, as determined by changes in the North Star Ambulatory Assessment score, after 12 months of treatment compared to placebo.
Other age-appropriate functional measures will also be assessed, such as time to stand, the four-stair climb, and 10-meter walk/run. Evaluations of growth progression, and cardiac and bone health will also be performed.
The trial design was supported and guided by discussions with the U.S. Food and Drug Administration (FDA), as well as by the input from physicians, patient organizations, and families of Duchenne patients.
“We are so glad to bring edasalonexent into Phase 3 for boys affected by Duchenne that could benefit from this potential therapy,” said Richard Finkel, MD, chief of the division of neurology, department of pediatrics at Nemours Children’s Health System and a principal investigator of edasalonexent trials.
“With the stabilization of muscle function and excellent safety profile seen with edasalonexent treatment in the MoveDMD trial, patients and families are eager for a treatment for Duchenne that has demonstrated slowed disease progression in the clinic,” he said.
Data from the Phase 1/2 MoveDMD trial (NCT02439216) and its open-label extension has shown that edasalonexent can effectively reduce the rate of functional decline in young DMD boys, preserving muscle function compared to placebo. The treatment was also reported to reduce levels of inflammation and of muscle fat accumulation.
Preclinical data, and clinical biomarker data from the MoveDMD trial, suggest that edasalonexent could have potential benefits in skeletal muscle, diaphragm and heart.
“PPMD [Parent Project Muscular Dystrophy] has conducted preference studies of those impacted by Duchenne to understand what is most important for novel therapies. Families responded that their highest priority is to stop or even slow disease progression and maintain muscle function,” said Pat Furlong, founding president and CEO of PPMD. “We are enthusiastic to see edasalonexent, with these potential effects, entering the Phase 3 PolarisDMD trial as an oral therapy that could treat all of those affected by Duchenne.”
Edasalonexent has been granted orphan drug, fast track, and rare pediatric disease designations by the U.S. Food and Drug Administration, as well as an orphan medicinal product designation by the European Commission.