The first treatment for levodopa-induced dyskinesia — the involuntary and jerky movements that afflict most Parkinson’s disease patients on this common therapy — was approved Thursday, Aug. 24, by the U.S. Food and Drug Administration.
The therapy, Gocovri (amantadine) by Adamas Pharmaceuticals, is an long-acting and extended-release capsule, indicated for those receiving levodopa-based therapy, with or without other dopaminergic medications. These are drugs, that, like levodopa, affect the activity of the neurotransmitter dopamine. It is expected to become available by year’s end, and will be formally launched in January, the company said in an announcement.
Prolonged use of levodopa, a widely used and first-line treatment for Parkinson’s, disrupts the balance of neurotransmitters controlling motor function, leading to involuntary, jerky movements. Dyskinesia is a common and dose-limiting effect of levodopa therapy, and a majority of patients experience it after 10 years of treatment, and as many as one in every two after five years, research shows.
“Dyskinesia can significantly compromise quality of life for people with Parkinson’s disease,” Dr. Todd Sherer, chief executive officer of The Michael J. Fox Foundation for Parkinson’s Research, said in a press release.
“Gocovri’s approval is an important advancement for the treatment of Parkinson’s disease, as it is the first FDA-approved medicine for the treatment of dyskinesia in Parkinson’s disease patients,” added Rajesh Pahwa, MD, director of the Parkinson’s Disease Center of Excellence at the University of Kansas Health System.
Adamas is setting up a patient services program, “Gocovri Onboard,” to provide financial assistance, reimbursement support, and help with prescriptions and treatment access to patients in need.
The FDA’s decision was based on a clinical research program — including three randomized and placebo-controlled trials involving a total of 286 patients — that evaluated the safety and efficacy of Gocovri in reducing involuntary movements caused by levodopa. The drug was taken at bedtime, which helped maintain its levels during morning and waking hours, when dyskinesia usually occurs.
EASED (NCT01397422), a Phase 2/3 study, was designed to evaluate the tolerability and efficacy of three dose levels of Gocovri, then known as ADS-5102 extended-release capsules, compared to placebo in 83 Parkinson’s patients with levodopa-induced dyskinesia.
Data published in May 2015 showed that ADS-5102 reduced dyskinesia by 27 percent compared to placebo, and significantly increased levodopa’s “on time” (the time a patient goes without Parkinson’s symptoms after taking a medication) without dyskinesia.
The EASE LID Phase 3 trial (NCT02136914) assessed the safety and effectiveness of ADS-5102 extended-release in a 340 mg dose, given to Parkinson’s patients with levodopa-induced dyskinesia for 24 weeks.
Results from this pivotal trial, reported in a study published in June, showed that the medication significantly improved levodopa-induced dyskinesia at 12 weeks (37% vs 12% in placebo), with the improvements remaining significant at 24 weeks. Gocovri also increased patients’ on time without dyskinesia by 40 percent, and reduced off time by about 45 percent. Off time is the period when the effects of levodopa wear off, and patients experience more Parkinson’s-related symptoms.
Another Phase 3 study, EASE LID 3 (NCT02274766), also assessed the safety and efficacy of the Gocovri capsules against placebo, given a similar patient population. As with the two other trials, Gocovri was seen to decrease the duration, intensity, and disability associated with dyskinesia at week 12. Off time was also reduced.
“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,” said Pahwa, who is also Laverne & Joyce Rider Professor of Neurology at the Kansas Medical Center. “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.”
The most common adverse reactions in Gocovri-treated patients included dizziness, hallucinations, dry mouth, edemas, and constipation.
An open-label safety and tolerability study (NCT02202551) involving Parkinson’s patients who completed the other trials is scheduled to conclude shortly.
“Today’s approval is a tremendous milestone for Adamas and for the Parkinson’s disease community,” said Gregory T. Went, PhD, founder, chairman and chief executive officer of Adamas Pharmaceuticals. “Gocovri has the potential to help people with Parkinson’s disease suffering from dyskinesia by finally providing physicians with an effective tool to address this long-standing unmet medical need. We thank the physicians, clinical staff, patients and their families who participated in the clinical trials for making this advancement possible for the community.”