Edaravone Demonstrates Less Functional Loss vs. Placebo in ALS Study
VANCOUVER, BC—At the 68th AAN Annual Meeting, a study found that edaravone use led to less functional loss than placebo, contrasting with results from a previous Phase 3 study where its efficacy did not statistically differ from placebo.
In a Phase 2 open-label study, edaravone showed a significantly less 6-month decline in functional loss as assessed by the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) compared to the decline in ALSFRS-R prior to edaravone treatment. A Phase 3 double-blind, placebo-controlled study (MCI186-J16) was then conducted in patients with ALS patients to confirm the safety and efficacy of edaravone during 6 cycles. In that study, the positive trend of edaravone did not significantly differ from placebo using the ALSFRS-R total score.
For the new study (n=137), researchers included patients with definite or probable ALS within 2 years of ALS onset, Japan ALS severity classification grade 1 or 2, baseline score ≥2 points on each ALSFRS-R item, baseline ≥80% forced vital capacity, and change in ALSFRS-R score during the 12-week pre-observation of -1 to -4 points.
The study patients were randomized to receive 6 cycles (24 weeks) of edaravone 60mg or matching placebo for 14 consecutive days followed by a 2-week drug-free period (Cycle 1), and then administration for 10 days over 2 weeks followed by a 2-week drug-free period (Cycle 2 and thereafter). The primary endpoint was change in the ALSFRS-R at Week 24 (6 months). Secondary endpoints included time to death or certain disease progression, percent forced vital capacity, modified Norris Scale, ALS Assessment Questionnaire, and grip/pinch strength.
Dr. Takeshi Sakata, from Mitsubishi Tanabe Pharma Co., Tokyo, Japan, stated, "As primary analysis, treatment with edaravone significantly differed from placebo" according to the ALSFRS-R (2.49±0.76; P=0.001). Consistent results were seen in post-hoc sensitivity analyses using an intent-to-treat (ITT) approach including all patient data. Also, researchers observed a favorable shift with edaravone treatment regarding distribution of change in ALSFRS-R scores from baseline to the end of Cycle 6. There was less functional loss in 3 subscores of ALSFRS-R vs. placebo with edaravone: limb (1.61±0.61; P=0.0087); bulbar (0.58±0.29; P=0.0448); respiratory (0.29±0.15; P=0.0593).
A similar rate of adverse events were noted in each group with 84.1% in the edaravone group vs. 83.8% in the placebo group. The most commonly reported adverse events for both groups were contusion, constipation, contact dermatitis, and dysphagia.
Overall, edaravone was associated with less functional loss and quality of life deterioration after 6 cycles vs. placebo among patients in early-stage ALS, Dr. Sakata concluded.