The U.S. Food and Drug Administration (FDA) has agreed to review a request by Adamas Pharmaceuticals to approve ADS-5102 (amantadine hydrochloride) extended-release capsules to treat levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease (PD).
The company submitted the request as New Drug Application (NDA) to the FDA in October.
A decision is expected by Aug. 24, based on the U.S. Prescription Drug User Fee Act. If approved, the medicine will be first available for PD patients with levodopa-induced dyskinesia, the most common dose-limiting adverse effect of levodopa therapy.
“This is an important milestone for patients, physicians and Adamas, as we are one step closer to approval of ADS-5102 for Parkinson’s disease patients with levodopa-induced dyskinesia, which is an existing gap in their treatment journey,” Gregory T. Went, PhD, chairman and chief executive officer of Adamas Pharmaceuticals, said in a press release. “Over time, 90% of patients on levodopa therapy suffer from levodopa-induced dyskinesia.”
The application is supported by a clinical research program that evaluated the compound’s efficacy and safety in patients. ADS-5102 is a chrono-synchronous amantadine therapy, used once a day at bedtime.
The clinical program included three placebo-controlled trials: EASED, and two Phase 3 trials, EASE LID and EASE LID 3.
EASED (NCT01397422) — a multicenter, randomized, double-blind, placebo-controlled, four-arm parallel group Phase 2/3 study — evaluated the tolerability and efficacy of three dose levels of ADS-5102 oral capsules given once daily to 83 PD patients with LID.
The Phase 3 EASE LID study (NCT02136914) — a Phase 3 multicenter, randomized, double-blind, placebo-controlled study — evaluated the safety and efficacy of a 340 mg dosage of ADS-5102 that was given to patients at bedtime for 24 weeks.
Data reported in April showed that the treatment resulted in statistically significant improvement in LID at 12 weeks, and that the improvements lasted for 24 weeks.
The EASE LID 3 study (NCT02274766) — a Phase 3 multicenter, randomized, double-blind, placebo-controlled, two-arm, parallel group study — evaluated the efficacy and safety of ADS-5102 once-daily, extended-release capsules, taken at bedtime, for the same clinical indication.
Data reported in September showed that the trial met its primary goal, with a reduction in the UDysRS (Unified Dyskinesia Rating Scale) total score at week 12, reflecting a decrease in the duration, intensity, and disability associated with LID. In addition, the results showed the treatment prompted a statistically significant reduction in off-time, as measured by patients’ diaries. Off-time is the period when Parkinson’s symptoms return once the effects of levodopa have worn off.
Overall, the results from the Phase 3 trials showed ADS-5102 reduced LID and off-time in PD patients, with a manageable safety and tolerability profile.
The NDA also is supported by data from EASE LID 2, an open-label study conducted EASED, EASE LID and EASE LID 3 patients, as well as those with LID who have received deep brain stimulation therapy. EASE LID 2 is ongoing, with patients being followed for as long as two years.