Extended-Release Amantadine Reduces Dyskinesia in Parkinson Disease Patients

Caroline Tanner, MD, PhD

An original version of this article was published by sister publication NeurologyLive.

A new amantadine (Gocovri) extended-release formulation could help treat levodopa-induced dyskinesia in patients with Parkinson disease.

In the two-year, 223-patient EASE LID 2 trial, a team led by Caroline Tanner, MD, PhD, professor of neurology at the University of California San Francisco, found that the new amantadine formulation is safe and tolerable long-term and results in the durable reduction of motor complications, which was defined by dyskinesia and off time.

In the treatment group, patients had lower Movement Disorder Society‐Unified Parkinson’s Disease Rating Scale (MDS‐UPDRS) Part IV scores at baseline that remained low over the duration of the study.

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.

Due to adverse events, 13.9% of patients in the study discontinued the study.

“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,” Tanner said in a statement. “These results expand not only our knowledge of Gocovri efficacy but also of its long-term safety in these patients.”

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

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 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 occurred more frequently in older age groups.

Ultimately, these adverse events were believed to be in part due to increasingly lower baseline estimated 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 adverse events, in type and frequency, to what was observed in phase 3 of its development, including hallucination.

The data ultimately suggested that dosing at greater than 274 mg at bedtime would be ideal for those who may be at heightened risk for adverse events.

The study, “EASE LID 2: A 2-Year Open-Label Trial of Gocovri (Amantadine) Extended Release for Dyskinesia in Parkinson’s Disease,” was published online in the Journal of Parkinson’s Disease.