Gocovri (amantadine) more than doubled the daily time on levodopa-based therapies without any dyskinesia — involuntary, uncontrolled movements — in people with Parkinson’s disease compared to those given a placebo, an analysis of data from two Phase 3 clinical trials showed.
The analysis was published in the journal Frontiers in Neurology in the study, “Amantadine ER (Gocovri®) Significantly Increases ON Time Without Any Dyskinesia: Pooled Analyses From Pivotal Trials in Parkinson’s Disease.”
Parkinson’s is characterized by a decline in dopamine in the brain, leading to a wide range of motor and non-motor symptoms.
Standard treatment is to replace dopamine with levodopa therapy. However, long-term use may lead to dyskinesia. People taking levodopa-based medicine can also experience an unpredictable re-emergence of stiffness and tremors between medication doses, referred to as “off” episodes.
Gocovri as extended release capsules, developed by Adamas Pharmaceuticals, is approved to treat dyskinesia in patients using levodopa-based therapies and as an add-on treatment for “off” episodes. Studies show Gocovri reduces levodopa-induced dyskinesias (LID, “on” episodes) and also significantly decreases “off” episodes while increasing the time on medication without troublesome dyskinesia, which interferes with daily activities or causes significant discomfort.
Clinical trials that supported Gocovri’s approval divided dyskinesia into ‘troublesome’ and ‘non- troublesome’ categories, based on patient-reported diaries. Still, given a choice, most people with Parkinson’s prefer no dyskinesia.
Researchers at the University of South Florida, working with scientists from Adamas, analyzed pooled Gocovri trial data to evaluate whether the therapy increased the time spent on levodopa-based therapies without dyskinesia — either troublesome or non-troublesome.
“Patients prefer to experience ON time without any dyskinesia, so balancing the need for levodopa-based treatment to reduce OFF time that comes with a risk of increased dyskinesia is a challenge for patient care in Parkinson’s disease,” Robert Hauser, a neurology professor at the university’s School of Medicine, said in a press release.
“These results expand the knowledge of Gocovri’s efficacy as an adjunctive treatment to levodopa to address both motor complications,” Hauser added.
Data from EASE LID (NCT02136914) and EASE LID 3 (NCT02274766) Phase 3 trials were examined, which evaluated Gocovri in patients who experienced “on” episodes of dyskinesia. Enrolled patients were randomly assigned to Gocovri or a placebo capsule once daily at bedtime.
As part of a secondary trial outcome, all patients kept home diaries for two days before each visit, in which they categorized their motor state as either “on” medication without dyskinesia, “on” with non-troublesome dyskinesia, “on” with troublesome dyskinesia, “off”medication, or asleep.
This study’s 196 enrolled patients ranged in ages between 34 and 82, with a mean time since Parkinson’s diagnosis of 9.7 years. They were using levodopa for a mean of 7.7 years, and had been experiencing levodopa-induced dyskinesia for a mean of 3.8 years.
Before starting Gocovri, patients reported — as baseline (pre-treatment) measures — a mean of 2.8 hours a day (h/day) of “off” time, 2.7 h/day of “on” time without dyskinesia, and 9.5 h/day of “on” time with dyskinesia. Troublesome dyskinesia while “on” medication was set at 4.9 h/day, and 4.6 h/day for non-troublesome dyskinesia.
After 12 weeks of Gocovri’s use, patients showed an increase in “on” time without dyskinesia, from a mean of 3.9 h/day at baseline to 8.4 h/day. A reduction in troublesome dyskinesia drove this result during “on” times, together with a decrease in “off” time symptoms.
As a comparison, those assigned placebo also showed an increase in “on” time without dyskinesia. But this was due solely to a decrease in “on” time with troublesome dyskinesia, whereas “off” time symptoms increased.
Consistently, time “on” medication with both troublesome and non-troublesome dyskinesia dropped in the Gocovri group from 9.4 hours at baseline to 5.3 hours after 12 weeks of treatment. For those in the placebo group, total time with dyskinesia decreased from 9.7 hours at baseline to 7.4 hours.
The proportion of “on” time with troublesome dyskinesia also showed a reduction in the Gocovri group, from 50% of total dyskinesia time at baseline to 26%, compared with 54% at baseline and 42% for placebo patients.
Overall, a statistically significant improvement was recorded in Gocovri-treaded patients relative to placebo for “on” time with dyskinesia, “on” time without dyskinesia, and for “on” time with troublesome dyskinesia and “off” time.
Further analysis found the treatment difference compared to mean baseline scores for the entire group represented about a 79% increase in “on” time without dyskinesia, which included a 29% increase in” on” time without troublesome dyskinesia. A 30% reduction in “on” time with troublesome dyskinesia and a 36% decrease in “off” time symptoms were also reported.
Distribution assessment of patient response by treatment group showed over half (53%) of Gocovri-treated patients had a 50% or greater reduction in time spent “on” medication with both troublesome and non-troublesome dyskinesia, while 27% had a 75% or more decline. Notably, 13% of patients treated with Gocovri had no recorded “on” time with dyskinesia at week 12 compared to 7% in the placebo group.
Patient responses showed over half (53%) of those on Gocovri had a 50% or greater reduction in time spent “on” medication with dyskinesia, both troublesome and non-troublesome, while 27% had a 75% or more decline. Notably, 13% of the Gocovri-treated group had no recorded “on” time with dyskinesia at week 12, compared to 7% in the placebo group.
Finally, significantly more Gocovri-treated patients experienced a greater portion of their waking day as “on” and without troublesome dyskinesia or any dyskinesia than did placebo patients. Likewise, the proportion of treated participants spending 50% or more of their waking day “on” without dyskinesia rose from 5% to 56% after 12 weeks, compared with 6% to 23% in the placebo group.
“In summary, results of these pooled analyses show a robust effect of Gocovri in increasing time patients spend ON without dyskinesia by reducing overall motor complications including time spent ON with both troublesome and non-troublesome dyskinesia as well as time spent OFF,” the researchers wrote.
“This publication highlights Gocovri’s ability to improve ON time with no dyskinesia — which can make a significant impact on better movement control for someone living with [Parkinson’s] motor complications,” said Adrian Quartel, chief medical officer at Adamas.
“As the only treatment that addresses both ends of the spectrum in [Parkinson’s] motor complications, we are proud to publish data that continue to support Gocovri as a treatment option that may help people with Parkinson’s increase good movement throughout the day,” Quartel added.
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