The novel formulation of edaravone, which was approved in May 2017, will be assessed in a cohort of 150 patients with amyotrophic lateral sclerosis for 48 weeks of treatment.
Carlayne Jackson, MD
A long-term phase 3 study set to assess the safety and tolerability of an investigational oral suspension formulation of edaravone in individuals with amyotrophic lateral sclerosis (ALS) has been initiated, according to Mitsubishi Tanabe Pharma America (MTPA).1
Edaravone, which was approved under the brand name Radicava in May 2017 for the treatment of ALS, is administered as an intravenous (IV) solution. This new oral suspension formulation somewhat marks a trend in ALS of developing oral agents to circumvent administration challenges, with a recent oral film formulation of riluzole getting FDA approval this month.2
“ALS presents a tremendous burden to patients as the disease robs them of physical function,” Carlayne E. Jackson, MD, professor of neurology and otolaryngology, UT Health Science Center, and US principal investigator, said in a statement. “As a researcher and provider of care for ALS patients, I’m pleased to be part of a research effort with a goal to provide a new treatment option for those living with this devastating disease.”
This open-label, multicenter, global study will include 150 patients with ALS at 65 sites, lasting for 48 weeks of treatment. After a screening period of 21 days the study will enroll those aged 18 to 75 years and follow the same dosing regimen as the IV formulation for this oral suspension.
“Enrollment of the first patient in this clinical study marks an important milestone for our company as we continue to seek treatment options for the ALS community,” Atsushi Fujimoto, president, MTPA, said in a statement. “There is a great unmet need in the area of ALS, and we believe an oral formulation of edaravone could potentially serve as an alternative treatment option for patients suffering from this progressive condition.”
The study will include primary safety assessments of adverse events, physical examination, electrocardiogram parameters, vital signs, laboratory safety assessments, unsteadiness, and sensory evaluations. Exploratory end points are expected to include the change in ALS Functional Rating Scale-Revised (ALSFRS-R) score, change in percentage of forced vital capacity (FVC), and time (days) to tracheostomy or permanent assisted mechanical ventilation.
In the 137-patient study that was the basis for approval of IV edaravone, there was a least-squares mean change of —5.01 (standard error [SE], 0.64) from baseline for ALSFRS-R scores with the neuroprotective drug compared with a change of –7.50 (SE, 0.66) for placebo, for a 2.49-point difference (SE, 0.76; 95% CI, 0.99–3.98; P = .0013). This represented a 33% improvement in ALSFRS-R with edaravone versus placebo.3
Treatment-emergent adverse events (AEs) were reported in 84% (n = 58) of patients receiving edaravone and 84% (n = 57) of patients receiving placebo. In total, 16% (n = 11) of those in the edaravone group and 24% (n = 16) of those in the placebo group had serious AEs, while 1% (n = 1) receiving edaravone and 6% (n = 4) receiving placebo had AEs (1 dysphagia in edaravone group; 1 dyspnoea, 2 respiratory disorder, and 1 rash in the placebo group) that led to withdrawal.
1. Mitsubishi Tanabe Pharma America Announced Initiation of Phase 3 Study Evaluating Investigational Oral Formulation of Edaravone for ALS [press release]. Jersey City, NJ: MTPA; Published November 25, 2019. mt-pharma-america.com/wp-content/uploads/2019/11/Mitsubishi-Tanabe-Pharma-America-Announces-Initiation-of-Phase-3-Study-Evaluating-Investigational-Oral-Formulation-of-Edaravone-for-ALS.pdf Accessed November 26, 2019.
2. Bigica A. Riluzole Oral Film FDA-Approved for Amyotrophic Lateral Sclerosis. NeurologyLive website. Published November 22, 2019. neurologylive.com/clinical-focus/riluzole-oral-film-fdaapproved-for-amyotrophic-lateral-sclerosis. Accessed November 26, 2019.
3. The Writing Group on behalf of the Edaravone (MCI-186) ALS 19 Study Group (2017). Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16(7):505-512. doi: 10.1016/S1474-4422(17)30115-1.