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FDA Approves Gocovri, First Drug to Treat Dyskinesia in Parkinson’s Patients
The FDA has approved a new version of an old drug—amantadine—as the first treatment for dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications. The FDA had granted extended-release amantadine capsules (Gocovri, Adamas Pharmaceuticals, Inc.) orphan drug status for this indication.
Dyskinesia, a consequence of levodopa-based Parkinson’s disease treatment, is characterized by involuntary and nonrhythmic movements that are purposeless and unpredictable, which impact the activities of daily living.
Gocovri (previously known as ADS-5102) is a high-dose 274 mg amantadine (equivalent to 340 mg amantadine hydrochloride [HCl]) taken once daily at bedtime that delivers consistently high levels of amantadine from the morning and throughout the day when dyskinesia occurs.
Amantadine has multiple mechanisms of action, including acting as an NMDA receptor antagonist and as a mild dopamine agonist. Gocovri is a proprietary extended-release formulation of amantadine HCl with a unique “chronotherapeutic” profile characterized by a slow initial increase in amantadine plasma concentrations; this is why the medication is expected to provide high plasma concentrations during the day and low plasma concentrations overnight.
“Notably, Gocovri is the first Parkinson’s disease medicine proven in controlled trials to reduce both dyskinesia and off-time in Parkinson’s disease patients receiving levodopa. Treatment of dyskinesia and off-time continues to be an unmet need in the medical management of Parkinson’s disease and the approval of Gocovri is a major step in that direction,” said Rajesh Pahwa, MD, Director of the Parkinson’s Disease Center of Excellence at the University of Kansas Health System.
Gocovri’s positive benefit and safety profile was established in two phase 3 controlled clinical trials in Parkinson’s disease patients with dyskinesia. In Study 1, patients treated with Gocovri demonstrated statistically significant and clinically relevant reductions in dyskinesia, with a 37% reduction in Unified Dyskinesia Rating Scale (UDysRS) total score versus 12% for placebo at week 12. These results were confirmed in Study 2, in which Gocovri achieved a 46% reduction in UDysRS versus 16% for placebo.
Additionally, key secondary data from Parkinson’s disease patient-reported diaries in Study 1 and Study 2, respectively, showed that Gocovri-treated patients experienced a 3.6 and 4.0 hour increase in functional time daily (defined as on-time without troublesome dyskinesia) versus a 0.8 and 2.1 hour increase for placebo-treated patients at week 12. The increases in functional time were achieved by decreases in both on-time with troublesome dyskinesia and off-time. The placebo-adjusted reduction in off-time in both studies was approximately one hour per day. The most commonly observed adverse reactions (more than10% and greater than placebo) with Gocovri were hallucinations, dizziness, dry mouth, peripheral edema, constipation, fall, and orthostatic hypotension.
Gocovri is expected to be available in the fourth quarter. Adamas has created “Gocovri Onboard,” a patient services program that will facilitate access and distribution, including reimbursement support and financial assistance.
Amantadine HCl was initially developed as an antiviral medication to treat influenza in the 1960s, and was coincidentally realized to be a treatment for Parkinson’s disease. It has been used in combination with levodopa to treat dyskinesias.
Sources: Adamas Pharmaceuticals, Inc.; August 24, 2017; National Parkinson Foundation; EASED Study; June 2013.