Enrollment is progressing quickly in Catabasis Pharmaceuticals‘ pivotal Phase 3 PolarisDMD trial, testing its investigational small molecule therapy edasalonexent for Duchenne muscular dystrophy (DMD) — with sites in some countries already full, the company said.
Screening is ongoing in the U.S., Canada, Australia, the U.K., Ireland, Sweden, Germany, and Israel for the trial, which is evaluating the safety and efficacy of capsules of edasalonexent, designed to treat all forms of DMD. The trial (NCT03703882) is active in all planned countries, with 37 sites open for enrollment, the company said.
Top-line results are expected in the second half of 2020 and are anticipated to support a New Drug Application filing in early 2021.
The update was shared at the Parent Project Muscular Dystrophy (PPMD) 2019 Annual Conference, held June 26-30 in Orlando, Fla.
“We are very pleased with the progress made in our Phase 3 PolarisDMD trial for edasalonexent in Duchenne. There has been significant interest from families and enthusiasm from investigators globally, and enrollment is going very well with some countries already at capacity,” Joanne Donovan, MD, PhD, chief medical officer of Catabasis, said in a press release.
“We appreciate the hard work of our study sites and the commitment of participating families as we look to develop a new treatment to benefit all boys affected by Duchenne,” she said.
Edasalonexent (formerly CAT-1004) is an investigational oral small molecule that blocks a signaling route called the NF-kappa B pathway. This pathway is an important link between loss of dystrophin protein and disease progression in DMD. It plays a fundamental role in skeletal and cardiac muscle breakdown.
The U.S. Food and Drug Administration (FDA) granted edasalonexent orphan drug, fast track and rare pediatric disease designations. The European Commission (EC) also granted the therapy orphan medicinal product designation for the treatment of DMD.
The PolarisDMD trial is a year-long, randomized, and placebo-controlled study, evaluating the effectiveness and safety of edasalonexent in boys with DMD. Catabasis plans to enroll approximately 125 patients, ages 4 to 7, regardless of mutation type, who have not been on steroids for at least six months.
The primary efficacy goal is improvement in motor abilities — measured by North Star Ambulatory Assessment score — after one year of treatment with edasalonexent, compared with placebo.
Other key secondary endpoints include timed function tests, adapted to each age. These include the time to stand, 4-stair climb, and 10-meter walk or run tests.
For each boy receiving placebo, two boys will receive a total of 100 mg per kilogram body weight, per day. The medicine will be given as three capsules per day. After one year, all boys in the trial are expected to receive edasalonexent in the open-label extension study, GalaxyDMD (NCT03917719).
“There is clear need for a therapy that could benefit all boys affected by Duchenne, regardless of mutation type, by slowing disease progression while being well tolerated. We are glad to be participating in the Phase 3 PolarisDMD trial for edasalonexent and are pleased that Kennedy Krieger is a top enrolling site,” said Kathryn Wagner, MD, PhD, the trial’s principal investigator.
“We have found the PolarisDMD trial to be thoughtfully designed to be family friendly as well as straightforward for our clinical team,” said Krieger, director of the Center for Genetic Muscle Disorders at the Kennedy Krieger Institute, and a professor at the Johns Hopkins School of Medicine.
At 25th annual PPMD conference, Catabasis also shared data from the MoveDMD Phase 2 open-label extension study (NCT02439216). That study evaluated the safety, efficacy, and pharmacokinetics — how a treatment distributes and is eliminated in the body — of edasalonexent in boys ages 4 to 8 with DMD.
At 72 weeks of treatment, patients given edasalonexent showed preserved muscle function, and substantially slowed DMD progression, compared with an off-treatment period.
Preclinical and biomarker data from the trial also suggests that edasalonexent may have benefits for skeletal muscle, diaphragm (an important breathing muscle), and heart. The treatment also was seen to be well-tolerated.
Updated data from a recent project collecting the views of nearly 30 U.S. physicians treating boys with DMD, caregivers, and patient advocacy representatives, also was presented.
One of the key observations was that DMD community members favored treatments that will go beyond skeletal muscle, and benefit additional aspects of DMD, including heart and pulmonary function.
Participants also shared their hope that treatments will provide durable benefits and improve quality of life. Physicians predicted that most patients will receive combination therapy within the next few years.