Analyses: Gocovri Works Better to Lessen Off Episodes, Dyskinesia
Several new clinical trial data analyses support the benefits and superiority of Gocovri (amantadine) over other therapies in lessening off episodes — periods when levodopa treatments stop working and motor symptoms return — and involuntary movements called dyskinesia in people with Parkinson’s disease.
The findings are being presented in five posters at the International Parkinson and Movement Disorder Society (MDS) Virtual Congress 2021, held online Sept. 17-22.
“We are pleased to present several analyses of different published clinical studies to highlight the importance of choosing the appropriate treatment options to address motor complications in Parkinson’s disease,” Adrian Quartel, MD, Adamas’ chief medical officer, said in a press release.
“Gocovri’s clinical results continue to demonstrate its unique and meaningful treatment impact on both OFF and dyskinesia — including through indirect comparisons with other levodopa-adjunctive treatments and amantadine-based products,” Quartel said.
Parkinson’s is characterized by the loss of dopamine-producing nerve cells, those responsible for releasing the neurotransmitter dopamine, a chemical messenger that allows nerve cells to communicate and, among other functions, helps regulate movement. A decline of dopamine in the brain leads to a wide range of motor and non-motor symptoms.
Replacement of dopamine with levodopa is currently the standard treatment for Parkinson’s. However, people taking levodopa-based medicines for long-term use often develop dyskinesia and may experience an unpredictable re-emergence of stiffness and tremors between medication doses. These periods are referred to as “off” episodes.
Gocovri was the first therapy approved in the U.S. for levodopa-induced dyskinesia. Its extended-release capsules treat involuntary movements in patients using levodopa-based therapies and are used as an add-on treatment for off episodes.
Now, researchers conducted a post-hoc analysis — looking at data after a study has concluded — of two Phase 3 clinical trials, EASE LID (NCT02136914) and EASE LID 3 (NCT02274766), which enrolled Parkinson’s patients who were randomly assigned to Gocovri or a placebo capsule once daily at bedtime. The results of that analysis are being reported in a poster titled “Amantadine DR/ER Efficacy as Early Add-On for Motor Complications in Parkinson’s Disease.”
The analysis focused on two subgroups, totaling 196 patients. Among them, 44 were treated with levodopa alone at the time they joined the trials, and 27 developed motor complications and joined the studies within five years of a Parkinson’s diagnosis. Nine patients fulfilled the criteria of both subgroups.
The results showed that patients treated with levodopa alone showed an increase in on time without dyskinesia similar to what was seen earlier in the overall trials. The improvements were even greater in the subgroup of patients diagnosed for less than five years when compared with the earlier reported results for all patients. This was driven by a reduction in troublesome dyskinesia and a decrease in off time symptoms.
The findings support the benefits of Gocovri “as a first add-on to levodopa for patients with early motor complications,” the researchers wrote.
“Gocovri as an only/early add-on treatment to levodopa showed reductions of OFF and dyskinesia that were similar to, or greater than, those seen in the overall trial population,” said Quartel.
Two other posters assessed the potential benefits of Gocovri in patients who may be candidates for device-aided therapies, and the medicine’s impact on daily activities in people with Parkinson’s.
In a poster titled “Should Amantadine DR/ER be Considered Prior to Device-Aided Therapies for Parkinson’s Disease?” researchers conducted a post-hoc analysis of pooled data from 63 patients enrolled in the EASE LID and EASE LID 3 trials.
All of the patients, who had a mean age of 53 at diagnosis, had advanced Parkinson’s, according to pre-defined criteria — specifically, more than five doses of levodopa, two hours or longer of off time, and one hour or more of dyskinesia per day — and were potential candidates for device-aided therapies to manage motor complications.
Of the 63 patients, 30 received Gocovri and 23 a placebo for 12 weeks, or about three months. The results showed that Gocovri increased on time without troublesome dyskinesia by a mean of 2.8 hours compared with placebo.
According to the researchers, these results suggest that Gocovri “should be considered in patients otherwise eligible for device-aided therapies.”
Another poster, “Amantadine DR/ER-related Reduction in OFF and Dyskinesia Improved Patient-Rated Interference with Activities and Social Interactions,” presented analysis results that showed that Gocovri significantly reduced patients’ off time and dyskinesia and had a positive impact on their daily activities.
Dyskinesia was measured using the Unified Dyskinesia Rating Scale (UDysRS) score system. Each item in the UDysRS is rated on a 0–4 scale, with higher scores mean more severe impact.
By the end of the 12-week treatment, the percentage of patients in the subgroup given Gocovri who reported that dyskinesia had a substantial impact and interfered with at least one of their daily activities had decreased from 63.4% at the trial’s start to 15.9%, the results showed. Meanwhile, the corresponding reduction in the placebo group was from 64.4% to 42.5%.
Two other posters compared clinical data to evaluate the effectiveness of Gocovri to add-on levodopa therapies.
Titled “Indirect Treatment Comparison of Adjunctive Treatments for Patients with Parkinson’s Disease Experiencing Motor Complications,” one poster compared Gocovri with several treatments, including deep brain stimulation (DBS), AbbVie’s Duopa — a levodopa-carbidopa intestinal gel also called Duodopa — and several other oral therapies.
Those therapies included Impax Pharmaceutical’s Rytary, which are carbidopa-levodopa extended-release capsules; Newron Pharmaceutical’s Xadago (safinamide); Bial and Neurocrine Biosciences’ Ongentys; Nourianz, marketed by Kyowa Hakko Kirin Pharma; and UCB’s Neupro patches, a rotigotine transdermal system that’s placed on the skin. Of note, Impax is now part of Amneal Pharmaceuticals.
The analysis showed that Gocovri and DBS led the more significant improvements, with a reduction of off time and dyskinesia by more than 30% when compared with a placebo. Specifically, off time was reduced by 36% with Gocovri and 44% with DBS, while on time with troublesome dyskinesia was reduced by 30% with Gocovri and 54% with DBS.
Oral dopaminergic treatments and Neupro reduced off time by 15-29% compared with the placebo. In patients given any of the oral treatments, dyskinesia increased by 12-31%, the analysis showed.
Gocovri was the only medication to significantly reduce both off time and on time with troublesome dyskinesia and was similar to DBS in its effectiveness.
The final poster, “Analysis of Amantadine Formulations for OFF and Dyskinesia in Parkinson Disease,” compared the effectiveness of Gocovri with other formulations of amantadine. These formulations included amantadine immediate release (IR) and amantadine IR/extended release (IR/ER, sold as Osmolex).
The results showed that Gocovri reduced off time by 36% and dyskinesia by 27%. Meanwhile, other formulations led to a more modest reduction in off time, by 19%, and dyskinesia, by 13%.
Moreover, only Gocovri led to a statistically significant reduction in off time while providing significant improvements in dyskinesia. These improvements were associated with the early morning amantadine levels — relative to bedtime administration — not observed for the other two formulations.
Taken together, the analyses support the use of Gocovri for Parkinson’s patients, according to Adamas.
“Overall, we are pleased to offer patients a non-surgical treatment option that increases their GOOD ON time and doesn’t necessitate a trade-off between treating OFF or dyskinesia,” Quartel said.