Amantadine ER Capsules Reduce Dyskinesia in Parkinson Over Long-Term


Final results of the EASE LID 2 study suggest that amantadine (Gocovri; Adamas) extended-release capsules are safe and effective over a 2-year treatment period.

Dr Caroline Tanner

Caroline Tanner, MD, PhD, professor of neurology, University of California San Francisco

Caroline Tanner, MD, PhD

Adamas Pharmaceuticals has announced that the final results of its 2-year, open-label trial of its amantadine formulation (Gocovri) extended-release capsules in the treatment of levodopa-induced dyskinesia in patients with Parkinson disease.1

The 2 year, 223-patient trial, dubbed EASE LID 2, suggested that treatment with the amantadine resulted in long-term safety and tolerability, as well as a durable reduction in the motor complications—defined by dyskinesia and off time. All told, those in the treatment group had lower Movement Disorder Society‐Unified Parkinson’s Disease Rating Scale (MDS‐UPDRS) Part IV scores were lower at baseline and remained low over the course of the trial.2

“As the longest-running amantadine study to date, this open-label trial suggests Gocovri may provide sustained improvement in both dyskinesia and off [time] to a wide cohort of patients with Parkinson’s disease living with motor complications,” said lead author Caroline Tanner, MD, PhD, professor of neurology, University of California San Francisco, in a statement. “These results expand not only our knowledge of Gocovri efficacy but also of its long-term safety in these patients.”

READ MORE: Investigational Dyskinesia Treatment Gets FDA Green Light

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.

“These newly published results suggest that Gocovri may reduce dyskinesia and OFF as far out as 100 weeks, providing sustained benefits to patients with levodopa-induced dyskinesia. Given the chronic nature of Parkinson’s disease, both patients and physicians seek treatments that are effective long-term,” said Jean Hubble, MD, vice president of medical affairs, Adamas, in a statement. “This study further demonstrates that the only FDA-approved medicine for dyskinesia may help people with Parkinson disease who are struggling to manage these levodopa-related motor complications over this long period of time.”

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.

These data add to prior findings presented in late 2019 at the 2019 International Congress of Parkinson’s Disease and Movement Disorders (MDS), in Nice, France, which highlighted the impact of amantadine on dyskinesia in patients with Parkinson disease receiving levodopa-based treatment from its post-marketing and development data.3

In 3 of the posters, safety data for the dopamine agonist was presented, including findings through 1 year after its FDA approval. Additionally, combined phase 3 data from 2 trials (NCT02136914 and NCT02274766) showed that the treatment was associated with significantly improved motor skills in 82 patients treated with the extended-release capsules compared to the 87 treated with placebo. One analysis of amantadine revealed the safety profile of the therapy was consistent, though adverse events (AEs) occurred more frequently in older age groups. Ultimately, these AEs were believed to be in part due to increasingly lower baseline glomerular filtration rates older patients, suggesting that clinicians should be mindful of renal function and overall morbidity and should consider lower dosing options for older patients.

Other safety presented at MDS of the agent 1-year post commercial launch showed similar AEs, in type and frequency, to what was observed in phase 3 of its development, including hallucination. The data ultimately suggested that dosing at <274 mg at bedtime would be ideal for those who may be at heightened risk for AEs.


1. 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 February 11, 2020.

2. Tanner CM, Pahwa R, Hauser RA, et al. EASE LID 2: A 2-Year Open-Label Trial of Gocovri (Amantadine) Extended Release for Dyskinesia in Parkinson’s Disease. J Parkinson Dis. Published online January 6, 2020. doi: 10.3233/JPD-191841.

3. Adamas Announces New Safety and Efficacy Data for GOCOVRI® in Parkinson’s Disease Patients with Dyskinesia at the Movement Disorder Society 2019 International Congress [press release]. Emeryville, CA: Adamas Pharmaceuticals; Published September 20, 2019. Accessed February 11, 2020.

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