Gocovri Approved by FDA as 1st Treatment for Levodopa-induced Dyskinesia in Parkinson’s Patients

Gocovri Approved by FDA as 1st Treatment for Levodopa-induced Dyskinesia in Parkinson’s Patients

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.”

3 comments

  1. Gocovri (extended-release amantadine) will undoubtedly be priced much higher than immediate-release amantadine, which has been available for many years as an inexpensive generic. The studies described in this article all compared Gocovri with placebo. Are there studies comparing the effects of Gocovri versus immediate-release amantadine taken in divided doses? Does generic amantadine have any significant benefit, compared with placebo, on dyskinesia or off time when taken in divided doses or in a single bedtime dose?

    • Ines Martins, PhD says:

      Hi David

      A study published in JAMA Neurology this month, revealing results from the EASE LID study, discusses some of your questions in detail. You can find the study here: http://jamanetwork.com/journals/jamaneurology/fullarticle/2630682.

      The team points that Gocovri provides continuous coverage throughout the day to alleviate levedopa-induced dyskinesia (LID), with high plasma concentrations that cannot be achieved with conventional dosing (100 mg 2 or 3 times daily) with immediate-release (IR) amantadine. They also say that the durability of IR amantadine effects are not well characterized, and while patients tolerate the equivalent of 200 mg Gocovri, higher doses are associated with an increased frequency of central nervous system adverse events.

      Nevertheless, no trials have ever compared the effects or immediate-release and extended-release amantadine, which would be required to draw any conclusions on the benefits of Gocovri over generic amantadine.

      • I already take two medications which are available as cheap generics in immediate-release (ir) form (Sinemet and Requip), but have switched to the newer extended-release (er) capsules, in order to gain some marginal benefit, as seen in clinical trials. The new er form of sinemet is rytary, which gains about an hour per day of “on time without troublesome dyskinesia” in trials comparing Rytary to Sinemet ir. I also saw studies in which Rytary beat Sinemet er. What was not tested was the real-world comparison of best management with Sinemet ir and Sinemet er compared with Rytary. I have tried switching back and forth between Rytary versus Sinemet ir/er dual therapy, and I am not sure there is any significant benefit to the former, particularly since Rytary 61/245 costs me about $1.24 per capsule, versus a few cents for Sinemet ir 25/100 plus Sinemet er 50/200. Is it worth it for me to pay over $25 per day in extra medication cost just to pick up a few minutes of on time without dyskinesia? The answer depends on the state of my med-battered wallet and my dyskinesia-battered body.

        In the same way, the Gocovri study compares amantadine er with placebo, and while you present convincing arguments about why amantadine er should be superior to amantadine ir, the only way to find out how much better LID patients do taking Gocoveri versus amantadine ir is to compare the two regimens in a controlled study. Can I significantly reduce dyskinesia by using Rytary plus Requip XL plus Gocoveri, a regimen which will probably cost about $600 per month for all 3 branded extended-release meds, versus my best all-generic priced regimen of Sinemet ir plus Sinemet er plus requip ir plus amantadine ir, which costs about a dollar a day total. (Note: Requip ir is available as a cheap generic, but Requip XL is expensive because the delivery system is under patent. Also, Sinemet ER is a cheap generic, but is said to have unpredictable and variable release kinetics compared with rock-steady Rytary).

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