Long-term Function and Survival of Radicava ORS® (Oral Edaravone)-Treated Patients With ALS vs Propensity Score–Matched PRO-ACT Historical Controls
Fumihiro Takahashi1, Angela Genge2, Takatomo Yoneoka3, Manabu Hirai1, Daniel Selness1, Vesna Todorovic4, Art Wamil1, Nissim Sasson5, Stephen Apple1, Ushirogawa Yoshiteru3
1Mitsubishi Tanabe Pharma America, Inc., 2Montreal Neurological Institute and Hospital, 3Mitsubishi Tanabe Pharma Corporation, 4Mitsubishi Tanabe Pharma Europe, Ltd, 5NStat Solutions, Biostatistical Services
Objective:
Investigate function and survival of Mitsubishi Tanabe Pharma America (MTPA) oral edaravone-treated patients enrolled in MTPA oral edaravone studies vs propensity score–matched Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) historical placebo patients.
Background:
On/off dosing regimens of Radicava® (edaravone) IV (intravenous; MTPA) and Radicava ORS® (edaravone) oral suspension (MTPA, hereafter “MTPA oral edaravone”) were US FDA-approved for ALS treatment in 2017 and 2022, respectively. Placebo-controlled trials showed MTPA IV edaravone slows functional decline in patients with ALS vs placebo, though no studies have investigated function and survival of MTPA oral edaravone vs placebo.
Design/Methods:
Study MT-1186-A01, a phase 3, open-label, 48-week study, evaluated long-term safety and tolerability of MTPA oral edaravone approved on/off dosing, Study MT-1186-A03 was its 96-week extension. Study MT-1186-A02, a phase 3b, double-blind, parallel group study that randomized patients to once daily or approved on/off MTPA oral edaravone regimen, Study MT-1186-A04 was its 48-week extension. Patients from Studies MT-1186-A02/A04 and Studies MT-1186-A01/A02/A03/A04 were propensity score–matched 1:1 on 10 baseline variables with historical, external PRO-ACT placebo patients (not receiving active investigational treatment in their respective clinical trials).
Results:
Studies MT-1186-A02/A04 showed statistically significant differences (P=0.005) with MTPA oral edaravone treatment for time to death vs matched PRO-ACT placebo patients (n=78). Baseline risk-adjusted hazard ratio showed an 84% decreased risk of death in MTPA oral edaravone vs placebo (P=0.005). ALSFRS-R total score change from baseline at week 48 was −8.42 points (MTPA oral edaravone) vs −14.05 points (PRO-ACT placebo) (P<0.001). In an analysis over approximately 34 months, patients from Studies MT-1186-A01/A02/A03/A04 (n=210) showed a 7.3-month prolongation of survival (P<0.001) vs propensity score–matched PRO-ACT placebo patients.
Conclusions:
Analysis of MTPA oral edaravone–treated patients with ALS from MT-1186 studies suggests MTPA oral edaravone significantly increases survival and decreases functional decline vs PRO-ACT placebo.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.