Amantadine Doubles Daily ON Time Without Dyskinesia in Parkinson Disease
Just over half (53%) of patients treated with the amantadine extended-release agent had greater than 50% reduction in time spent ON with dyskinesia and just over a quarter (27%) of patients had greater than 75% reduction.
Robert A. Hauser, MD, MBA
Results from 2 pivotal, placebo-controlled phase 3 clinical studies, EASE LID (NCT02136914) and EASE LID 3 (NCT02274766), demonstrated that treatment with amantadine extended release (amantadine ER; Gocovri; Adamas Pharmaceuticals) more than doubled the daily time patients with Parkinson disease (PD) spent ON without dyskinesia.1,2
The pooled analysis included 196 patients, who went from 3.9 hours/day of ON time without dyskinesia to 8.4 hours/day at week 12. Treatment effects were statistically significant for amantadine ER vs placebo starting at week 2 and were sustained until week 12.
Using mixed model repeated measures (MMRM), patients in the amantadine group at week 12 showed an adjusted mean increase over placebo of 2.9 (±0.6) hours in ON time without dyskinesia (Cohen d effect size, 0.79) and an adjusted mean decrease of –1.9 (±0.6) hours in ON time with dyskinesia (Cohen d effect size, 0.49).
"Patients prefer to experience ON time without any dyskinesia, so balancing the need for levodopa-based treatment to reduce OFF time that comes with a risk of increased dyskinesia is a challenge for patient care in Parkinson disease,” Robert A. Hauser, MD, MBA, professor of neurology and director of the Parkinson’s Disease and Movement Disorders Center at the University of South Florida, said in a statement. “These results expand the knowledge of Gocovri’s efficacy as an adjunctive treatment to levodopa to address both motor complications.”
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Data also showed a 1.5-hour (±0.4) placebo-adjusted reduction in ON time with troublesome dyskinesia and a 0.6-hour (±0.4) reduction in ON time with non-troublesome dyskinesia. Notably, researchers observed that patients treated with amantadine had OFF time reduced by 1.0 hours (±0.3) compared to placebo.
Consistent with results above, time spent ON with dyskinesia decreased in the amantadine group from 9.4 hours (±3.4) at baseline to 5.3 hours (±4.4) at week 12, whereas in the placebo group, total time with dyskinesia decreased from 9.7 hours (±3.2) at baseline to 7.4 hours (±4.2) at week 12. The proportion of ON time with dyskinesia that was rated as troublesome also showed a greater reduction for amantadine, from 50% of total dyskinesia time at baseline to 26% at week 12, compared with 54% at baseline and 42% at week 12 for placebo.
As well, at week 12, more than half (56%) of amantadine-treated patients spent more than 75% of the walking day ON without troublesome dyskinesia compared with 28% of patients in the placebo group. Furthermore, the percentage of patients with no reported ON time with troublesome dyskinesia at end point was 16% for amantadine compared with 1% for placebo.
"This publication highlights Gocovri’s ability to improve ON time with no dyskinesia—which can make a significant impact on better movement control for someone living with PD motor complications,” Adrian Quartel, MD, chief medical officer, Adamas, said in a statement.1 “As the only treatment that addresses both ends of the spectrum in PD motor complications, we are proud to publish data that continue to support Gocovri as a treatment option that may help people with Parkinson’s increase good movement throughout the day.”
In 2017, amantadine was approved as the first and only medicine indicated for the treatment of dyskinesia in patients with PD receiving levodopa-based therapy, with or without dopaminergic medications. Most recently in February 2021, the drug received its second indication, which allows it to serve as an adjunctive treatment to levodopa/carbidopa in patients with PD who experienced OFF episodes.3
Adamas also previously released data on EASE LID 2, its 2-year, open-label trial of amantadine in February 2020, which showed long-term safety and tolerability, as well as a durable reduction in the motor complications of PD.4
Those results showed that at baseline, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale 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 (DBS) group. By Week 8, every group had similar scores—amantadine: 6.3; placebo: 6.2; DBS: 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 DBS groups, respectively.
