The following article is part of conference coverage from the 8th Joint American Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) MSVirtual2020 event. Neurology Advisor‘s staff will be reporting breaking news associated with research conducted by leading experts in neurology. .
The extended release capsule form of amantadine (ADS-5102), FDA approved as Gocovri for the treatment of dyskinesia in Parkinson disease, displayed a dose-response for both tolerability and efficacy. This suggests potential clinically meaningful benefits for walking speed in patients with multiple sclerosis (MS), according to study results presented at the 8th Joint American Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) MSVirtual2020 event, held September 11-13, 2020.
The pharmacokinetic profile of ADS-5102 enables once-daily bedtime dosing, providing a higher drug concentration throughout the day and lower concentrations at night. This phase 3 study, INROADS, was designed to assess the benefits of ADS-5102 on walking speed in patients with MS, as well as the drug’s safety.
The INROADS study began with 4 weeks of placebo followed by 12 weeks of double-blind testing. Of 594 patients from Canada or the United States with MS and walking impairment, 560 were randomly assigned, 1:1:1, to placebo (n=186), 274 mg ADS-5102 (n=185), or 137 mg ADS-5102 (n=187). The primary study endpoint was the proportion at week 16 showing a statistically significant increase in response rate. This was defined as ≥20% improvement from baseline in timed 25-foot walk [T25FW], measured in feet/second, compared to performance on placebo. Patients without an assessment at week 16 were considered nonresponders.
At week 16, 274 mg ADS-5102 displayed 21.1% (P =.01) improvement, 137 mg ADS-5102 displayed 17.6% (P =.08) improvement, and placebo displayed 11.3% improvement in response rate. Results indicated that 274 mg ADS-5102 met the primary objective of a statistically significantly greater response rate vs placebo. Among the subjects completing the study, response rates were 11.9% for placebo vs 28.3% (P <.001) for 274 mg, and 19.6% (P =.049) for 137 mg. Most observed adverse events (AEs) included dry mouth, peripheral edema, constipation, urinary tract infection, fall, and insomnia. These AEs led study researchers to discontinue the study for 20.5% of 274 mg participants, 6.4% of 137 mg participants, and 3.8% of placebo participants.
Study investigators concluded, “INROADS met its primary objective of showing clinically meaningful benefit in MS walking speed for 274 mg ADS-5102. A dose-response was seen for both efficacy and tolerability.” They added that observed AEs matched the known safety profile of amantadine, and that results indicated that ADS-5102 may help “improve walking in patients in MS, particularly those who have tried and discontinued dalfampridine.”
Visit Neurology Advisor‘s conference section for continuous coverage from the ACTRIMS/ECTRIMS MSVirtual2020 Forum.
Cohen J, Cameron M, Goldman M, et al. Phase 3 Study Results Assessing the Efficacy and Safety of ADS-5102 (Amantadine) Extended Release Capsules in MS Patients With Walking Impairment. Presented at: 8th Joint American Committee for Treatment and Research in Multiple Sclerosis and European Committee for Treatment and Research in Multiple Sclerosis MSVirtual2020 event; September 11-13, 2020; Poster P0225.