FDA Approves Amantadine Hydrochloride for Dyskinesia

The US Food and Drug Administration (FDA) has approved the first and only drug for the treatment of dyskinesia in Parkinson's disease (PD) patients.

Amantadine hydrochloride (GOCOVRI), an extended-release capsule developed by Adamas Pharmaceuticals, was approved Thursday by the FDA for treating dyskinesia in PD patients receiving levodopa-based therapy. Dyskinesia, the neurologic disorder characterized by uncontrolled movement that can result in sleep disturbances, can be developed by the use of dopamine promoter levodopa.

GOCOVRI is also being considered by Adamas for other chronic neurologic disorders, such as multiple sclerosis (MS) and post-stroke walking impairment, tardive dyskinesia (TD), and other indications in PD.

Adamas supported the new drug's efficacy and safety with data from 3 comprehensive Phase III registration studies — EASED, EASE LID, and EASE LID 3. The studies featured 286 levodopa-induced dyskinesia (LID) patients, with 121 (42%) receiving a once-daily 340mg dose of GOCOVRI, versus a placebo-controlled group.

The trials met primary and secondary endpoints. An open-label study for LID patients from the trials who had also undergone deep brain stimulation therapy is currently ongoing, under the name EASE LID 2. Patients in the study will be followed up for 2 years.

The FDA previously designated LID in PD patients as an orphan disease, meaning it affects less than 200,000 people nationwide. Nevertheless, GOCOVRI is the first drug in the US or Europe to have been approved for dyskinesia in PD patients being treated with levodopa, with or without concomitant dopaminergic medications.

It joins valbenazine (Ingrezza) for TD as a sole medication for side-effect conditions of movement disorder treatments. Ingrezza was approved for TD treatment in April this year, after having been fast-tracked by the FDA. It was backed by over 20 clinical trials at the time, Chris O’Brien, MD, chief medical officer at Neurocrine Sciences, told MD Magazine.

Researchers had known for more than a decade that the VMAT2 protein in the brain was capable of regulating dysfunctional movement control system in the basil ganglia, O'Brien said. Treatments for dyskinesia mean addressing its primary effect.

"The challenge is these involuntary movements," O'Brien said. "They affect the mouth, the tongue, the jaw, the limbs, the trunk. They add to the stigma of mental illness. This is really hard for patients because often the result is social isolation."

Dyskinesia carries a similar trait from PD in that patients offer suffer from sleep disorders, which GOCOVRI was also tested to treat. The benefit of a good, consistent sleep is exponential to a movement disorder patient, Aleksandar Videnovic, MD, associate professor at Massachusetts General Hospital, told MD Magazine.

"Patients who have a good night of sleep experience much less troublesome symptoms of Parkinson's disease the following day," Videnovic said. "Perhaps, even responsiveness to the medications they take for the symptoms is better after a good night of sleep."

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