July 13, 2018
A global Phase 3 trial evaluating the efficacy and safety of oral edasalonexent in patients with Duchenne muscular dystrophy (DMD) will begin enrolling boys, ages 4 to 7, in the coming months, Catabasis Pharmaceuticals announced.
Top-line results from this trial, to be called POLARIS, are expected in April 2020, and this data may be used to support a request for edasalonexent’s approval to treat DMD, a company press release states.
Edasalonexent, developed by Catabasis, is a small molecule designed to inhibit the NF-κB protein that promotes muscle damage and prevents muscle regeneration in Duchenne MD.
It is being developed as a potential disease-modifying therapy for all patients, regardless of their underlying disease-causing mutation.
POLARIS expects to enroll 125 patients with different dystrophin mutations; those eligible will not be on steroid therapy for at least six months before enrollment. Boys being treated with eteplirsen (Exondys 51, by Sarepta Therapeutics) may be eligible to participate.
Patients will be randomized, 2:1, to receive edasalonexent or a placebo for 12 months. They will then be invited to continue in an open-label study extension, where all will be treated with edasalonexent.
Researchers will determine treatment efficacy — the study’s primary goal — by measuring changes in motor skills as evidenced using the North Star Ambulatory Assessment score at the study’s end and compared to placebo patients.
Additional, or secondary, objectives will be patient scores on other function tests, including time-to-stand, the four-stair climb, and 10-meter walk/run test. Boys’ growth, heart and bone heath will also be analyzed.
The design of the POLARIS trial — done in consultation with the U.S. Food and Drug Administration (FDA) — is similar to Catabasis’ ongoing Phase 1/2 MoveDMD (NCT02439216) study, which has reported promising results. According to data shared at a recent neurology conference, edasalonexent treatment at almost one year at the study’s higher dose (100 mg/kg) resulted in a statistically significant delay in disease progression, and lower inflammation and muscle fat accumulation (as DMD patients age, fat deposits build in muscles and lead to greater impairment).
Treatment benefits in this high-dose group were significant after 12 weeks of treatment, and maintained for 48 weeks or study end.
“We have designed a robust study with POLARIS DMD to evaluate edasalonexent as a potential new treatment for Duchenne. We have benefited from input from many people that are part of the Duchenne community and we are well underway with our preparations to begin the trial,” Joanne Donovan, chief medical officer of Catabasis, said in the release.
Edasalonexent is being developed as a single therapy, but also as a possible combination with other treatments that work to increase the levels of dystrophin.
“We are very excited to advance edasalonexent through this potentially last phase of clinical development with the hope of providing a new treatment option to all boys affected by this disease. We believe that edasalonexent has great potential as a therapy to be taken on its own as well as in combination with other treatments,” Donovan added.
The European Commission and the FDA have both designated edasalonexent an orphan drug as a potential DMD treatment, and the FDA has also placed it on fast track — raising the possibility of a quicker regulatory review.