Gocovri is now the only therapy to be approved in the US to treat both off episodes and dyskinesia in patients with Parkinson disease.
Adamas Pharmaceuticals has announced that the FDA has approved a second indication for amantadine (Gocovri) extended-release capsules, which can now serve as an adjunctive treatment to levodopa/carbidopa in patients with Parkinson disease (PD) experiencing OFF episodes.1
This second indication is based off a supplemental new drug application (sNDA) that contained data from 2 pivotal, placebo-controlled phase 3 studies that showed that treatment with amantadine significantly reduces both OFF time and dyskinesia. Patients with PD who received the drug in those trials showed a clinically meaningful increase in good ON time while on levodopa-based medication.
In 2017, amantadine was originally 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.
"The approval of a second indication for Gocovri is a major milestone for patients with Parkinson’s who experience motor complications in their daily lives. Gocovri is now the first and only medication approved to treat both OFF and dyskinesia motor complications in Parkinson’s disease,” Neil F. McFarlane, chief executive officer, Adamas, said in a statement.
Data from a post-hoc analysis of the 2, phase 3 studies (NCT02136914; NCT02274766) were submitted for the 2020 American Academy of Neurology (AAN) Annual Meeting. Among the 198 patients enrolled in the trial, 101 (51%) of those composing the OFF subgroup had dyskinesia and ≥2.5 hours of daily OFF time. At baseline, the mean OFF time was 4.4 hours and ON time with troublesome dyskinesia was 4.6 hours. At week 12, placebo-adjusted change in OFF time was a reduction of 1.2 hours (P <.001) and troublesome dyskinesia was reduced by 2.0 hours (P <.001).2,3
The sNDA, which was accepted for review by the FDA in June, also included data from the 2-year, 223-patient trial–dubbed EASE LID 2 (NCT02202551), which showed that treatment with amantadine resulted in long-term safety and tolerability, as well as a durable reduction in the motor complications, defined by dyskinesia and off time.4
In that study, those in the treatment group demonstrated lower Movement Disorder Society, Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part IV scores at baseline and remained low over the course of the trial. 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 (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.5
Safety analysis showed that 13.9% of patients discontinued the study because of adverse events (AEs) considered to be related to amantadine. Falls, hallucinations, peripheral edemas, constipation, and urinary tract infections were among the most common AEs.
Regarding the FDA approval, Adrian Quartel, MD, chief medical officer, Adamas, said in a statement, “the extensive clinical trial evidence for Gocovri supports its unique ability to reduce OFF episodes and dyskinesia in people with Parkinson’s disease who are on levodopa/carbidopa therapy. Many PD medications necessitate a trade-off between reducing OFF time and exacerbating levodopa-induced dyskinesi. Gocovri is the first medication to reduce both.”