The FDA accepted the new drug application for priority review, setting a PDUFA action date of May 12, 2022.
The FDA has accepted a new drug application (NDA) for an investigational oral formulation of edaravone (MT-1186) for the treatment of amyotrophic lateral sclerosis (ALS), Mitsubishi Tanabe Pharma America (MTPA) recently announced. A Prescription Drug User Fee Action data has been set for May 12, 2022, as the application was accepted for priority review.1
The intravenous (IV) formulation of edaravone (Radicava; MTPA) was approved by the FDA for treatment of ALS in May 2017, with the investigational oral formulation developed to have a similar clinical profile. The NDA was supported by data from the IV edaravone pivotal trial, Study 19 (NCT01492686), which found that early intervention with the treatment reduced death, tracheostomy, permanent assisted ventilation, and hospitalization in patients with ALS. The 24-week double-blind period compared IV edaravone with placebo, followed by a 24-week open-label period where all patients received IV edaravone.2
“At MTPA, we thrive on tackling the toughest challenges and are focused on addressing the unmet needs of the ALS community, which is illustrated by our ongoing development program for edaravone," Atsushi Fujimoto, president, MTPA, said in a statement.1 "Our top priority is to help ensure ALS patients have flexibility with treatment and formulation options that are right for their specific needs. We look forward to working with the FDA in the coming months to bring this new formulation to patients as soon as possible.”
A series of phase 1 studies comparing the oral formulation and IV formulation of edaravone were completed by MTPA in 2019. A phase 3 clinical trial (NCT04165824) has also been initiated to evaluate the safety and tolerability of the oral formulation, enrolling 185 patients with ALS at 50 different sites in the US, Canada, Europe, and Japan. The safety extension study of the trial (NCT04577404) is also underway to evaluate long-term safety and tolerability of oral edaravone for up to 96 weeks.
"Oral edaravone may provide another formulation option for ALS patients looking for an alternate mode of administration," Terry Heiman-Patterson, MD, professor of neurology, Lewis Katz School of Medicine, Temple University, and director, Temple MDA/ALS Center of Hope, said in a statement.1 "We know that every patient living with ALS has their own unique needs, and I'm hopeful that an oral suspension formulation will offer a new and much needed option."
At the Motor Neurone Disease Association 32nd International Symposium on ALS/motor neurone disease (MND), held virtually from December 7-10, 2021, details from the phase 4 REFINE-ALS biomarker study (NCT04259255) in patients with ALS were presented. The trial is anticipated to enroll approximately 300 patients with ALS who have begun treatment with IV edaravone.3
The 24-week study will include a total of 6 treatment cycles, each spanning 28 days, with 60 mg of edaravone administered by intravenous (IV) infusion for 14 days of the initial treatment cycle and followed by daily dosing on 10 out of 14 days in subsequent cycles. Biomarkers will be assessed for oxidative stress, inflammation, and neuronal and muscle injury, prior to treatment initiation, at treatment start, and again at cycles 1, 3, and 6 over the course of the study period.
Due to the COVID-19 pandemic, protocol amendments were implemented in January 2021, allowing patients to participate virtually via telemedicine rather than visiting hospitals or attending office visits. Samples are collected by trained nurses either at the clinic or at patients’ homes, then processed and shipped to a central collection company.