Phase 3, Open-Label, Multicenter Safety Study of Oral Edaravone in Patients With Amyotrophic Lateral Sclerosis (MT-1186-A01): 48-Week Results (P6-4.001)

Abstract

<h3>Objective:</h3> Study MT-1186-A01 assessed the safety and tolerability of oral edaravone (MT-1186) in patients with ALS. NCT04165824. <h3>Background:</h3> An intravenous (IV) formulation of edaravone (Radicava®/Radicut) has been shown to slow the rate of physical functional decline in amyotrophic lateral sclerosis (ALS). Radicava ORS® (edaravone) oral suspension was recently approved by the US Food and Drug Administration for use in patients with ALS. <h3>Design/Methods:</h3> Study MT-1186-A01 was a global, multicenter, open-label, phase 3 study that evaluated the long-term safety and tolerability of oral edaravone in patients with ALS. The primary safety analysis was assessed at weeks 24 and 48. Patients received a 105-mg dose of oral edaravone administered in treatment cycles that replicated IV edaravone dosing. <h3>Results:</h3> In the safety analysis population (n=185), the most common treatment-emergent adverse events (TEAEs) reported by ≥5% of patients were fall (22.2%), muscular weakness (21.1%), constipation (17.8%), dyspnea (10.8%), dysphagia (10.3%), and back pain (10.3%). TEAEs considered to be study drug-related were reported by 46/185 (24.9%) patients, with the most common being fatigue (3.2%), dizziness (2.7%), headache (2.2%), and constipation (2.2%). Serious TEAEs were reported by 48/185 (25.9%) patients, with the most common being worsening of ALS symptoms (6.5%), dysphagia (3.2%), dyspnea (2.7%), and respiratory failure (2.7%). TEAEs leading to death were reported in 12/185 (6.5%) patients, including respiratory failure (2.2%), worsening of ALS (1.1%), pneumonia (1.1%), acute respiratory failure (0.5%), lung disorder (0.5%), diabetic ketoacidosis (0.5%), feeding disorder (0.5%), and suicide (0.5%). TEAEs leading to discontinuation were reported by 2/185 patients (tremor, n=1; gait disturbance, n=1); both TEAEs considered by the investigator to be study drug-related. No serious TEAEs, or TEAEs leading to death, were study drug-related. <h3>Conclusions:</h3> This study demonstrates that oral edaravone was generally safe and well tolerated during 48 weeks of treatment, with no new safety concerns identified. <b>Disclosure:</b> Dr. Genge has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AL-S Pharma. Dr. Genge has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Genge has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cytokinetics. Dr. Genge has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amylyx. Dr. Genge has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Quralis. Dr. Genge has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Genge has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MTPA. Dr. Genge has received personal compensation in the range of $0-$499 for serving as a Consultant for WAVE. The institution of Dr. Pattee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MTPA pharmaceuticals. The institution of Dr. Pattee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MTPA pharmaceiticals. The institution of Dr. Pattee has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Catalyst. The institution of Dr. Pattee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for General Dynamics US military. The institution of Dr. Pattee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Otsuka pharmaceuticals. Dr. Sobue has nothing to disclose. Dr. Couratier has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Couratier has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Couratier has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier . Mr. Selness has received personal compensation for serving as an employee of Mitsubishi Tanabe. Mr. Bidani has received personal compensation for serving as an employee of Mitsubishi Tanabe Pharma Development America Inc. Manabu Hirai has received personal compensation for serving as an employee of Mitsubishi Tanabe Pharma Corporation. Takeshi Sakata has received personal compensation for serving as an employee of Mitsubishi Tanabe. Alejandro Salah has nothing to disclose. Stephen Apple has received personal compensation for serving as an employee of Mitsubishi Tanabe Pharma America, Inc.