Gocovri (amantadine) is the only Parkinson’s disease therapy approved in the U.S. to treat both dyskinesia — the involuntary, jerky movements that can occur in patients using a levodopa-based therapy — and “off” episodes, or the periods when medications stop working and symptoms recur.
An oral medication developed by Adamas Pharmaceuticals — later acquired by Supernus Pharmaceuticals — Gocovri was initially approved by the U.S. Food and Drug Administration (FDA) in August 2017 as the first drug specifically indicated for treating dyskinesia.
The FDA then approved Gocovri in February 2021 as an add-on therapy for off episodes in people with the neurodegenerative disorder.
Gocovri is taken as an extended-release, long-lasting capsule once daily at bedtime.
How Gocovri works
The first line of treatment for Parkinson’s is levodopa therapy to replace dopamine, whose loss is the hallmark of the disease. Levodopa is naturally found in the body and is the precursor of dopamine, a neurotransmitter or signaling molecule that relays electric signals between nerve cells.
However, prolonged use of levodopa disrupts the balance of chemical messengers controlling motor function, leading to dyskinesia.
Gocovri is thought to work by increasing the levels of dopamine in the brain.
The exact mechanism by which Gocovri exerts its activity in the treatment of dyskinesia in Parkinson’s disease patients is unknown. However, the therapy has been shown to increase dopamine release and block dopamine re-uptake, thereby increasing the levels of this neurotransmitter in the brain.
Gocovri in clinical trials
The FDA’s approval of Gocovri to treat dyskinesia was based on data from three randomized placebo-controlled clinical trials involving 286 patients. These trials evaluated the safety and effectiveness of Gocovri in reducing involuntary muscle movements caused by levodopa. During the trials, patients took Gocovri at bedtime, which helped maintain dopamine levels during the morning and waking hours, when dyskinesia usually occurs.
A Phase 2/3 study (NCT01397422) called EASED was designed to evaluate the tolerability and effectiveness of three doses of Gocovri compared with a placebo in 83 Parkinson’s patients with levodopa-induced dyskinesia. The trial’s results showed the therapy significantly reduced dyskinesia compared with a placebo by 27% and increased levodopa’s “on” time, or the period in which a patient goes without Parkinson’s symptoms after taking medication.
A 24-week (or nearly six-month) Phase 3 trial called EASE LID (NCT02136914) assessed the safety and effectiveness of 340 mg of Gocovri, taken once daily at bedtime, in Parkinson’s patients with levodopa-induced dyskinesia. This trial found that the medication significantly improved levodopa-induced dyskinesia at 12 weeks, or about three months. The results, published in August 2017, showed a 37% decrease in symptoms compared with 12% among participants given a placebo — which was maintained through week 24. Gocovri also increased patients’ on time and delayed off episodes (when the symptoms return) by almost one hour compared with the placebo.
Another Phase 3 study (NCT02274766) called EASE LID 3 also showed that Gocovri decreased the duration and intensity of dyskinesia, and the disability associated with it, at week 12. Gocovri also reduced off episodes in that trial.
In each of these trials, neither the participants nor the researchers knew which patients were receiving Gocovri and which the placebo.
An open-label study, in which both investigators and participants were aware of the treatment being given, evaluated the long-term safety and tolerability of Gocovri over 105 weeks — about two years — in people with Parkinson’s who had levodopa-induced dyskinesia. The results of that trial (NCT02202551) were published in Movement Disorders Clinical Practices. The researchers indicated that their data suggested that Gocovri provided an incremental reduction in MDS-UDPRS Part IV score — a Parkinson’s disease rating scale used to evaluate clinical trial results — in patients without exacerbating adverse side effects.
For treating off episodes
Supported by the various trial results, notably those of EASE LID 3, Adamas filed a supplemental application with the FDA in 2020, asking that Gocovri be approved to treat off periods in patients using a levodopa-based therapy.
Off periods are characterized by the reappearance or worsening of symptoms, including tremor as well as dyskinesia.
In the application, Adamas also had cited data from the open-label, Phase 3 EASE LID 2 (NCT02202551) trial, which had confirmed that Gocovri, when given over a two-year period, safely and effectively reduced dyskinesia and off episodes in the different groups of patients followed in the study.
The approval by the FDA was announced on schedule with the date the agency had set the prior year.
The most common adverse side effects associated with using Gocovri were hallucinations, dizziness, dry mouth, constipation, falls, and low blood pressure when getting up from a sitting or lying position.
Page updated: Nov. 29, 2021
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