Amantadine Shows Treatment Durability for Reducing OFF Time in Parkinson Disease


The percentage of patients reporting no OFF time and no impact of OFF on daily function more than doubled by the first on-treatment visit in this open-label trial.

Caroline Tanner, MD, PhD

Data on the impact of amantadine (Gocovri; Adamas Pharmaceuticals), FDA-approved for levodopa-induced dyskinesia (LID) in patients with Parkinson disease (PD), remained favorable at the 2-year end point of the EASE LID 2 study (NCT02202551), according to an additional analysis presented at the 2020 MDS Virtual Congress, September 12–16, 2020.1

After previously showing significantly reduced OFF time in phase 3 trials, Caroline Tanner, MD, PhD, professor of neurology, University of California San Francisco, and colleagues aimed to evaluate the long-term effect of amantadine using distribution of Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part IV scores over 100 weeks of open-label treatment.

“In addition to the demonstrated improvement in dyskinesia, the percentage of patients reporting no OFF time and no impact of OFF on daily function more than doubled by the first on-treatment visit in this open-label trial and remained favorable at the 2-year trial endpoint,” Tanner et al. concluded.

EASE LID 2 included 223 participants, 212 of which had a recorded MDS-UPDRS Part IV score prior to amantadine treatment in either the double-blind or open-label phase. No OFF time at baseline was reported in 6.2% of patients, whereas 62.3% reported OFF time less than a quarter of the waking day, and 31.1% of patients reported OFF time more than a quarter of the waking day.

READ MORE: Levodopa-Carbidopa Intestinal Gel Superior to Immediate Release Capsules for ON Time Without Dyskinesia

By Week 8, 17.5% of patients were reporting no OFF time; that increased to 17.9% at Week 100. At baseline, 10.8% of patients reported no impact of OFF on social interactions and daily activities, which increased to 30.8% at Week 8 and 25.5% at Week 100.

Tanner and colleagues also found that fewer patients reported mild or greater functional impact of OFF time, decreasing from 64.6% pre-treatment to 39.4% at Week 8 and 49.2% at Week 100.

MDS-UPDRS Part IV scores for items 4.1 and 4.2, which measure daily time and functional impact of dyskinesia, also improved by week 8 through week 100.

Data from EASE LID 2 previously published in February included both safety and MDS-UPDRS scores for those who received amantadine, placebo, or deep brain stimulation.2

At baseline, MDS-UPDRS Part IV scores were a mean of 6.5 points for those continuing treatment with amantadine compared to 9.4 for the placebo group and 10.5 for the deep brain stimulation group. By Week 8, every group had similar scores—amantadine: 6.3; placebo: 6.2; deep brain stimulation: 6.4—and remained level for the amantadine group at Week 100 at 6.9 points compared to 7.3 and 7.0 for the placebo and deep brain stimulation groups, respectively.

As for safety, 13.9% of patients discontinued the study because of adverse events (AEs) considered to be related to amantadine, with the common AEs being falls, hallucinations, peripheral edemas, constipation, and urinary tract infections. Overall the median treatment duration for trial participants was 1.9 years.

Post-hoc analysis from the aforementioned phase 3 trials (NCT021136914; NCT02274766) were presented at this year’s American Academy of Neurology (AAN) Annual Meeting. Researchers noted that the improvement in good ON time was due to a reduction in the number of hours spent in OFF as well as the hours spent ON with troublesome dyskinesia. Patient-rated motor symptom impact on activities of daily living were significantly improved compared to placebo as shown by a –3.2 change on the MDS-UPDRS (P <.001).3

Amantadine extended-release capsules remain as the first and only FDA-approved medicine indicated for the treatment of dyskinesia in patients with PD receiving levodopa-based therapy, with or without concomitant dopaminergic medications. It is also the only medicine clinically proven to reduce both dyskinesia and OFF.

For more coverage of MDS 2020, click here.

1. Tanner C, Chernick D, Formella A. Long-term effects of ADS-5102 (amantadine) extended release capsules on OFF symptoms in Parkinson’s disease patients with levodopa-induced dyskinesia: analysis of EASE LID 2 trial. Presented at MDS Virtual Congress; September 12–16, 2020. Abstract 955.
2. Adamas Announces Publication of the Two-Year Phase 3 Open-Label EASE LID 2 Trial of GOCOVRI® for Dyskinesia in Patients with Parkinson’s Disease. [press release]. Emeryville, CA: Adamas Pharmaceuticals; Published February 11, 2020. Accessed September 14, 2020.
3. Adamas presents new post-hoc phase 3 data analysis for Gocovri in Parkinson’s disease at the 2020 American Academy of Neurology (AAN) science highlights platform [news release] Emeryville, CA. Adamas Pharmaceuticals. Published July 15, 2020. Accessed September 14, 2020.
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