Gocovri (amantadine) extended release oral capsules provided long-term improvements of motor complications in Parkinson’s disease patients, according to results from a Phase 3 clinical trial.
Gocovri, developed by Adamas Pharmaceuticals, is the only medication approved by the U.S. Food and Drug Administration for the treatment of dyskinesia — involuntary, jerky movements — in Parkinson’s patients who receive levodopa-based therapy, with or without accompanying dopaminergic medications.
“When coupled with the Phase 3 controlled studies, this completed open-label study provides supportive evidence that GOCOVRI was able to provide a treatment effect for up to 100 weeks, without waning of benefit in the majority of patients,” Robert Hauser, MD, professor of neurology and director of the USF Health Byrd Parkinson’s Disease and Movement Disorders Center, said in a press release.
EASE LID 2 (NCT02202551) was a two-year, open-label study that evaluated the long-term safety, tolerability, and effectiveness of Gocovri in Parkinson’s patients with levodopa-induced dyskinesia. Patients received the therapy once daily at bedtime.
The study enrolled 223 patients from three previous trials — EASED (NCT01397422), EASE LID (NCT02136914) and EASE LID 3 (NCT02274766 ) — which assessed and compared Gocovri’s effectiveness versus placebo-randomized controls.
Also included in the study were a subgroup of patients with uncontrollable dyskinesia who had deep brain stimulation — the most common surgery used to treat Parkinson’s symptoms by delivering electrical pulses to brain cells.
Researchers tested the therapy’s effectiveness by measuring patients’ clinical progression using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). This scale is divided into four parts: Part I focuses on non-motor experiences of daily living, Part II on motor experiences of daily living, Part III on motor examination, and Part IV on motor complications.
Results showed that by the end of the two-year treatment, patients’ scores on the MDS-UPDRS Part IV, assessing motor complications, showed a change of -2.4 units in patients previously treated with placebo, -3.5 units in patients who took amantadine immediate release, and -3.6 units in patients who had deep brain stimulation.
In patients who were already on Gocovri, changes in MDS-UPDRS, Part IV scores were less pronounced — only 0.4 units — confirming the therapy’s effectiveness even before long-term treatment.
“The completed Phase 3 open-label study further expands our understanding of the benefit/risk profile of GOCOVRI,” said Rajiv Patni, MD, chief medical officer of Adamas Pharmaceuticals. “The large reduction in dyskinesia and OFF, as assessed by the Part IV score of the MDS-UPDRS, was observed by the first visit at Week 8 and was sustained for two years. This durability is noteworthy given the known progression of motor complications.”
Gocovri’s safety profile is in line with previous reports. The most common adverse reactions included falls, hallucinations, peripheral edemas, constipation, and urinary tract infections, but these were generally mild to moderate. During the two-year study, 9% of the patients discontinued the treatment due to adverse effects, and nine patients died, although no death was linked to Gocovri.
“Nine percent of patients discontinued GOCOVRI due to an adverse drug reaction over this prolonged treatment period and the safety as well as tolerability remained consistent with that obtained from the 64-week data cut from December 2016,” Patni said.
“Lastly, by two years, 30 percent of patients increased their levodopa dose by an average of approximately 300 mg, suggesting that GOCOVRI treatment may allow neurologists to further optimize their patient’s levodopa dose despite the occurrence of dyskinesia,” he said.
These new findings will be presented at the 22nd International Congress of Parkinson’s Disease and Movement Disorders Oct. 5-9 in Hong Kong, China.
“These data suggest that further research is warranted to assess whether GOCOVRI could potentially delay the onset or reduce the progression of motor complications,” Hauser said.