Adamas Pharmaceuticals, Inc. (Nasdaq:ADMS) On 4/19/18 announced positive data from EASE LID 2, the company’s two-year Phase 3 open-label study of GOCOVRI™ (amantadine) extended release capsules, the first and only medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of dyskinesia in patients with Parkinson's disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications. Overall, results demonstrated that GOCOVRI was generally well tolerated and the treatment effect on motor complications (dyskinesia and OFF), as measured by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Part IV, was maintained for up to two years. This effect was seen in all subgroups, including those switched to GOCOVRI from placebo or amantadine immediate release (IR), as well as a subgroup of patients with uncontrollable dyskinesia after deep brain stimulation (DBS) treatment. These data are planned to be presented at the 22nd International Congress of Parkinson’s Disease and Movement Disorders (MDS) in Hong Kong, China.
“The completed Phase 3 open-label study further expands our understanding of the benefit/risk profile of GOCOVRI,” said Rajiv Patni, M.D., Chief Medical Officer of Adamas Pharmaceuticals, Inc. “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. 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. 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.”
“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,” stated Robert Hauser, M.D., MBA, Professor of Neurology, Director, USF Health Byrd Parkinson's Disease and Movement Disorders Center, Parkinson Foundation Center of Excellence. “These data suggest that further research is warranted to assess whether GOCOVRI could potentially delay the onset or reduce the progression of motor complications.”
This final analysis extends and confirms the previously reported results from the 64-week interim analysis published in the Journal of Parkinson’s Disease in 2017. At Week 100, the change from baseline in the MDS-UPDRS, Part IV, score was a decrease of -2.4, -3.5, -3.6 units, in patients previously treated with placebo, amantadine IR and DBS, respectively. In contrast, the change from baseline in the previously treated GOCOVRI patients was 0.4 units, demonstrating little change in patients who were already receiving GOCOVRI prior to entry in this open-label study.
The safety data are consistent with the previously reported safety profile of GOCOVRI, which includes precautions and warnings related to suicidality, hallucinations, dizziness and orthostatic hypotension. During the two-year study, nine percent of patients discontinued due to adverse drug reactions (ADRs). Most adverse drug reactions were of mild to moderate intensity, and the most common adverse drug reactions (≥5%) were falls, hallucination, peripheral edema, constipation, urinary tract infection, dizziness, nausea, insomnia, livedo reticularis, dry mouth, depression, anxiety and abnormal dreams. Nine patients died during the course of the study because of cardiac arrest, pneumonia, sepsis, or natural causes; none were deemed study drug related.