Extending Use of Edaravone for ALS Treatment
An extension trial assesses the efficacy and safety of extending edaravone treatment past the FDA-approved 6 cycles.
Edaravone received FDA approval based on trial data that assessed the use of edaravone for 6 cycles of treatment. The question is, can edaravone be used post 6 cycles? Would it be beneficial?
In May 2017, MT Pharma America (a subsidiary of the drug's developer Mitsubishi Tanabe Pharma Corporation) announced it presented open-label extension data that showed patients with amyotrophic lateral sclerosis (ALS) treated with edaravone for 48 weeks (12 cycles) experienced significantly less decline in physical function compared with patients given placebo for 6 months followed by 6 months of edaravone (measured by the ALS Functional Rating Scale-Revised [ALSFRS-R]). The findings were featured in an oral presentation at the European Network for the Cure of ALS annual meeting in Ljubljana, Slovenia. 1
The open label study was an extension to initial study MCI186-19 phase 3 trial that evaluated efficacy and safety of edaravone. The initial 6-month study period was followed by a 6-month open-label extension phase in which patients who were previously on placebo began active treatment with edaravone, and those who had been on edaravone continued for another six months.1
In the 6-month open label extension study, 123 of 137 patients were continued in this extension phase, 65 patients in edaravone-edaravone (E-E group), and 58 patients in placebo-edaravone (P-E group). The mean change (± SD) in the ALSFRS-R score from baseline in Cycle 1 to the end of Cycle 6 was —4.1 ± 3.4 in the edaravone group versus –6.9 ± 5.1 in the placebo group. The change from baseline in Cycle 1 to the end of Cycle 12 was –8.0 ± 5.6 in the E-E group versus –10.9 ± 6.9 in the P-E group. 2
The most commonly reported adverse effects (≥5% of patients in both treatment groups) were nasopharyngitis, respiratory disorder, constipation, dysphagia, and contusion. During the active-treatment period at least 1 adverse effect was reported in 81.5% of patients in the E-E group and 82.8% of patients in the P-E group. Of these patients, 26.2% and 39.7% were reported as serious, respectively. 2
The open label extension phase study noted that the ALSFRS-R score changed almost linearly throughout Cycles 1—12 in the E-E group. Suggesting possible benefit of continuing therapy as appropriate per patient status. Safety concerns were similar in both groups of the extension phase, with less serious events in the E-E group. The higher percentage of serious adverse effects in the P-E group may be due to progression of ALS. Due to limitations of statistical analysis performed in the open label study, a post hoc analysis was performed. A mixed model for repeated measures (MMRM) and the Combined Assessment of Function and Survival (CAFS) were assessed. 3 The MMRM analysis at 48 weeks showed significantly less decline in ALSFRS-R total score in the E-E group than in the P-E group (least-squares mean change from baseline ± standard error, 4.17 ± 1.40, p = 0.0037). Suggesting differences in ALSFRS-R total score were maintained in patients receiving edaravone for an additional 24 weeks. This was supported by CAFS endpoint, p = 0.0089.3
- MT Pharma America Presents 12-Month RADICAVATM (Edaravone) and Amyotrophic Lateral Sclerosis Data at the European Network for the Cure of ALS (ENCALS) Annual Meeting [news release]. Jersey City, NJ: May 18, 2018; MT Pharma. https://www.mt-pharma-america.com/wp-content/uploads/2017/05/MTPA-ENCALS-2017-Press-Release-Final_5.18.17.pdf Accessed 09 May 2018.
- THE WRITING GROUP ON BEHALF OF THE EDARAVONE (MCI-186) ALS 19 STUDY GROUP (2017) Open-label 24-week extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis,Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 18(sup1):55-63, DOI: 10.1080/21678421.2017.1364269. Published September 5, 2017. Accessed June 1, 2018.
- Takei K, Tsuda K, Takahashi F et al. Post-hoc analysis of open-label extension period of study MCI186-19 in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2017 Oct;18(sup1):64-70. doi: 10.1080/21678421.2017.1365372.