Long-term Function and Survival of Radicava ORS® (Oral Edaravone)-Treated Patients With ALS vs Propensity Score–Matched PRO-ACT Historical Controls

Topic:

Other

Poster Number: P283

Author(s):

Fumihiro Takahashi, PhD, Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey, USA, Angela Genge, MD, Clinical Research Unit, The Montreal Neurological Institute, Montreal, QC, Canada, Takatomo Yoneoka, MPharm, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan, Manabu Hirai, MS, Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey, USA, Daniel Selness, RN, BA, MBA, Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey, USA, Vesna Todorovic, MD, MPhil, Mitsubishi Tanabe Pharma Europe, Ltd, London, United Kingdom, Art Wamil, MD, PhD, Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey, USA, Nissim Sasson, MA, NStat Solutions, Biostatistical Services, Rehovot, Israel, Stephen Apple, MD, Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey, USA, Ushirogawa Yoshiteru, MPharm, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan

BACKGROUND: On/off dosing regimens of Radicava® (edaravone) IV (intravenous; Mitsubishi Tanabe Pharma America [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 compared to placebo, though no studies have investigated function and survival of MTPA oral edaravone vs placebo.

OBJECTIVES: Investigate function and survival of 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.

RESULTS: Study MT-1186-A01, a phase 3, open-label, 48-week study, evaluated long-term safety and tolerability of MTPA oral edaravone 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 patients (not receiving active investigational treatment in their respective clinical trials). Studies MT-1186-A02/A04 showed statistically significant differences (P=0.005) with MTPA oral edaravone 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 controls (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. CONCLUSION: 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.