The U.S. FDA has corresponded with Santhera Pharmaceuticals regarding Santhera’s proposed subpart H approval pathway of Raxone (idebenone) in patients with Duchenne muscular dystrophy (DMD) who are not taking concomitant glucocorticoids.
Santhera had proposed that results of the SIDEROS clinical trial provide confirmatory evidence of efficacy in these patients while at the same time, the trial would expand the label to include the treatment of patients using glucocorticoids.
“While we are disappointed that the FDA does not support our plan to file an NDA for Raxone under subpart H for patients not using concomitant glucocorticoids, we now have clarity that successful completion of the SIDEROS trial will provide the necessary data to support NDA filing for Raxone in all DMD patients irrespective of the glucocorticoid use status,” Santhera CEO Thomas Meier, PhD, said in a press release.
Previous clinical studies, such as the Phase 3 DELOS trial, have demonstrated that Raxone can successfully slow the loss of respiratory function and reduce bronchopulmonary complications.
The positive outcome of the study was published in The Lancet under the title “Efficacy of idebenone on respiratory function in patients with Duchenne muscular dystrophy not using glucocorticoids (DELOS): a double-blind randomised placebo-controlled phase 3 trial.”
Now, the Phase 3 SIDEROS clinical trial will evaluate Raxone only in DMD patients receiving concomitant glucocorticoids. Participants will receive either Raxone (900 mg/day; two tablets, three times a day with meals) or a placebo for 78 weeks (18 months). The primary endpoint is a change from baseline to week 78 in forced vital capacity percent predicted (FVC%p). Secondary endpoints include changes from baseline in percent predicted peak expiratory flow (PEF%p), time to first 10 percent decline in FVC and change from baseline in inspiratory flow reserve.
The double-blind, randomized, placebo-controlled trial will treat patients with declining respiratory function on any stable glucocorticoid treatment regardless of the underlying dystrophin mutation or ambulatory status.
Those who complete the trial will be eligible to enroll in an open label extension study where all patients receive Raxone. Results for the SIDEROS trial are expected by 2019.
The protocol of the SIDEROS trial had already been reviewed by the FDA with confirmation of the trial’s potential to provide the necessary efficacy data, along with data from previous trials. The FDA concluded that the results from the SIDEROS trial should be provided at the time of filing to support a New Drug Application (NDA) for the treatment of DMD patients, regardless of their corticoid use status.
“Enrollment in the SIDEROS trial will start shortly and we are committed to working closely with the FDA, clinical experts and the DMD patient community to make Raxone available for all DMD patients in the U.S. as quickly as possible,” Meier said.