Early Intervention With Edaravone in Study 19 Was Associated with Decreased Hospitalization, Tracheostomy, Ventilation, and Death in Patients with ALS

Clinical Trials
57
Benjamin Brooks MD, Takeshi Sakata , Fumihiro Takahashi PhD, Gustavo Suarez Zambrano MD, Bryan Hill PharmD, MBA, Melissa Hagan PhD, MPH, Stephen Apple MD
1. Atrium Health Neurosciences Institute, Carolinas Medical Center, University of North Carolina School, 2. Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan, 3. Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan, 4. Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey, 5. Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey, 6. Mitsubishi Tanabe Pharma America, Jersey City, New Jersey, 7. Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey

Background: The lifespan for patients with amyotrophic lateral sclerosis (ALS) is ~3 to 5 years from the time of onset, and the mortality rate is 50% within 30 months of symptom onset. In edaravone pivotal Study 19 in ALS patients, intravenous (IV) edaravone was associated with significantly less functional decline compared with placebo.

Objective: To assess the effects of IV edaravone on survival and additional milestone events in Study 19.

Approach: Post hoc analysis of Study 19, which included a 24-week double-blind period (edaravone vs placebo) followed by a 24-week open-label period with all patients receiving IV edaravone (ie, edaravone-edaravone [EE] vs placebo-edaravone [PE] groups). Survival analyses were conducted of the occurrence of milestone events, including death, tracheostomy, permanent assisted ventilation (PAV), and hospitalization due to ALS progression.

Results: There were no deaths during the double-blind period in Study 19. During the 24-week open-label period there were 2 deaths in the EE group receiving edaravone for 12 months and 4 in the PE group receiving edaravone after being on placebo. Survival analysis indicated that the hazard ratio (HR) for death was 0.48 (95% confidence interval [CI], 0.08-2.73) P=.4059 for the EE group vs the PE group. Similarly, survival analysis of the cumulative occurrence of death, tracheostomy, or PAV revealed a HR=0.44 (95% CI, 0.10-1.81), P=.2523. The addition of hospitalization to the survival analysis (ie, cumulative occurrence of death, tracheostomy, PAV, or hospitalization) demonstrated a 53% risk reduction in these events, which was statistically significant, with HR=0.47 (95% CI, 0.25-0.88), P=.0189.

Conclusions: This analysis may indicate that early intervention with IV edaravone was associated with significant reduction in the combined endpoint of cumulative occurrence of death, tracheostomy, PAV, and hospitalization in patients with ALS. Further research is recommended to confirm these findings.