Treatment with Radicava ORS (edaravone), an oral formulation of the established ALS therapy, has shown significant benefits in slowing disease progression and improving survival outcomes for individuals with amyotrophic lateral sclerosis (ALS). These findings were presented by Mitsubishi Tanabe Pharma America (MTPA) at the 2024 annual meeting of the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS).
Radicava ORS Efficacy and Survival Benefits
Data from multiple Radicava ORS trials, including the MT-1186-A01 Phase 3 trial and its extension study MT-1186-A03, were compared against the PRO-ACT database, which contains data from over 12,000 ALS patients in prior Phase 2/3 clinical trials. The analysis revealed that patients treated with Radicava ORS lived approximately two years longer than the placebo-treated controls from the PRO-ACT database. Furthermore, the medication reduced the likelihood of death by about 84%.
Additional analyses, encompassing data from all four trials, demonstrated that after nearly three years (35 months) of follow-up, only 13.8% of patients receiving Radicava ORS died, compared to 32.9% in the control group. This translated to a 7.3-month increase in survival and a 66% lower risk of death for patients treated with Radicava ORS.
"Results from analyses of the long-term function and survival of Radicava ORS versus propensity score-matched Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) historical controls in people with ALS suggest Radicava ORS increased survival outcomes and decreased physical function decline versus controls," said Gustavo A. Suarez Zambrano, MD, MTPA’s vice president of medical affairs.
Impact on Functional Decline
Changes in the ALS Functional Rating Scale Revised (ALSFRS-R) after approximately 48 weeks indicated a significantly slower decline in the ability to perform everyday tasks among the Radicava ORS group compared to controls. Researchers concluded that these analyses provide evidence for a slowing of functional decline and improved survival outcomes with long-term Radicava ORS treatment compared to PRO-ACT placebo group patients with ALS.
Radicava ORS Dosing Regimens
MTPA also sponsored a Phase 3b clinical trial (MT-1186-A02) and its extension (MT-1186-A04) to evaluate the efficacy and safety of a once-daily dosing regimen of Radicava ORS compared to the approved on/off dosing schedule over 48 weeks. The standard on/off regimen involves daily treatment for 14 consecutive days, followed by a two-week period without dosing, and subsequent cycles of 10 days of treatment followed by 18 days off.
Results indicated no significant differences in disease progression rates or survival outcomes between the daily treatment and the on/off schedule. However, 25% of patients receiving daily Radicava ORS experienced side effects related to the treatment, compared to 16.8% of those on the on/off regimen. Serious side effects, particularly trouble swallowing, were also more frequent with once-daily dosing.
The study findings support the conclusion that the on/off regimen of Radicava ORS is the most appropriate for patients with ALS, balancing efficacy with tolerability.
"These findings, along with final results from Study MT-1186-04, which support the continued use of the FDA-approved on/off regimen of Radicava ORS, further reinforce MTPA’s commitment to addressing unmet needs, advancing research, and driving scientific innovation in ALS," Suarez Zambrano added.
