Global Phase 3 Study of Oral Edaravone to Treat ALS Fully Enrolled

The Phase 3 clinical trial investigating an oral suspension formulation of edaravone (MT-1186) in treating amyotrophic lateral sclerosis (ALS) is now fully enrolled, the therapy’s developer, Mitsubishi Tanabe Pharma America, announced.

This open-label study (NCT04165824) first opened in November but paused in March due to the COVID-19 pandemic. It resumed patient dosing and recruitment in September, enrolling about 185 adults at study locations in the U.S., Europe, Canada, and Japan.

While Radicava, an intravenous formulation (given directly into the bloodstream) of edaravone, has been approved to treat ALS in the U.S. since 2017, an oral formulation could be attractive.

“With this oral edaravone Phase 3 study now fully enrolled, we are one step closer to reaching our goal of having an additional treatment option for patients,” Atsushi Fujimoto, president of MTPA said in a press release.

“We are grateful to the participants, the investigators and the clinical staff at the study sites as well as the MTDA staff working on this study,” Fujimoto added.

Edaravone works by reducing oxidative stress — an imbalance between the production of potentially harmful free radicals and the cells’ antioxidant defenses — which is thought to be one of the causes of nerve cell death in ALS.

Trial data support Radicava as safely and effectively slowing functional decline in people with ALS. But its recommended dosing regimen requires somewhat long infusion periods (about one hour long) and frequent visits to the clinic.

That last part is because Radicava is administered for 14 consecutive days, followed by a two-week treatment-free period. Subsequent treatment cycles consist of daily treatment for 10 of the next 14 days, again followed by two weeks without treatment.

The ongoing Phase 3 trial is exploring the safety and tolerability of the oral edaravone, given in the same dosing regimen as the intravenous formulation, for 48 weeks (nearly one year). It has no placebo group, meaning all enrolled patients will be treated.

Safety, determined by the occurrence and frequency of adverse events, is the trial’s main goal. Secondary measures consist of changes in participants’ ALS functional rating scale-revised (ALSFRS-R), a measure of disability, and the time until a patient needs an invasive procedure to prevent respiratory failure, or dies.

“ALS is a devastating, debilitating disease, and I am very pleased to be involved in this important research,” said Angela Genge, MD, a principal investigator for the trial. “The completion of enrollment for the study is a crucial step in our efforts to explore potential treatment options for these patients.”

Patients who finish this trial may choose to continue treatment in its long-term extension study (NCT04577404), where the oral treatment’s safety, tolerability, and efficacy will be evaluated for up to 96 weeks. These two studies are expected to support fillings to regulatory authorities requesting the approval of oral edaravone for ALS.

An additional Phase 3b study (NCT04569084), initially a post-approval trial further exploring Radicava’s safety and efficacy, will now also include patients on oral edaravone.

As a postmarketing commitment study, or a trial MTPA agreed to conduct to gather more information about its treatment’s safety, efficacy, and optimal use, data from this Phase 3b trial will not be part of the company’s anticipated request for oral edaravone’s approval.