Switch From Amantadine Immediate-Release to Gocovri Results in Improved Real-World Parkinson Disease Benefits

Real-world findings from the Axon Registry highlighted the therapeutic advantages of delayed- and extended-release amantadine (AMT-ER; Gocovri; Supernus) over immediate-release amantadine (AMT-IR), with patients reporting less Parkinson disease (PD) medication usage, fewer PD symptoms, and decreased overall dyskinesia. These findings were also true among those who switched from AMT-IR to AMT-ER, providing more context on the real-world use of AMT-ER.¹

Presented at the 4th Annual Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress, held by the PMD Alliance from June 27-30, 2025, the analysis comprised 146 patients with PD from the American Academy of Neurology Axon registry who met eligibility criteria. Of these, most patients continued AMT-ER for at least 3 months (>2 refills: n = 74 [50.7%]), with 47 (32.2%) having at least 6 months of follow-up data. Coming into the study, 122 (83.6%) patients used dopamine agonists pre-index, with 60.3% of these using AMT-IR.

Using electronic health record data, investigators found that while the median total number of PD medication classes used did not change pre vs post-index (median: 3), shifts were apparent, with fewer patients using at least 3 medications at 6 months. Senior author Heather E. Moss, MD, PhD, a professor of ophthalmology and neurology at Stanford Medicine, and colleagues, found that the most common reasons to switch from AMT-IR to AMT-ER were dyskinesias, followed by OFF time and wearing off. In addition, pre- and post-index data revealed a shift away from MAO-B inhibitors (63.8% vs 48.9%), COMT-inhibitors (31.9% vs 21.3%), and anticholinergics (8.5% vs 2.1%) following AMT-ER initiation.

Treatment with AMT-ER also had an impact on PD motor symptom presence, such as bradykinesia, tremors, and rigidity. In the study, patients had a median of 3 symptoms (IQR, 2-4) pre-index and a median of 0 (IQR, 0-2) at 3-6 months post-index. Notably, these decreases were observed in both the presence and severity of all reported PD symptoms. Following AMT-ER initiation, the percentage of patients with motor fluctuations (25.5% vs 21.3%) and dyskinesia severe enough to result in treatment change (61.7% vs 23.4%) was reduced.

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AMT-ER, marketed as Gocovri, was FDA-approved in 2017 as the first drug specifically indicated for levodopa-induced dyskinesia. Years later, in 2021, the agency approved an expanded indication for its use as an adjunctive treatment to levodopa/carbidopa in patients with PD experiencing OFF episodes. AMT-ER, a long-acting formulation of amantadine, works on the dopamine and glutamate brain chemical pathways.²

An indirect comparison analysis presented at the 2022 ATMRD Congress revealed that AMT-ER has more benefit in patients with PD than other formulations, including AMT-IR and immediate-release/extended-release tablets. Using predicted multiple-dose pharmacokinetic profiles of the different formulations, AMT-ER—administered in a dose of 274 mg at 10:00 PM—showed a markedly higher concentration between the hours of 6:00 AM and 10:00 AM, above 1200 ng/mL.³

In the analysis, AMT-ER demonstrated the most significant benefit, with a 27.3% improvement in UDysRS scores and a 36.1% reduction in OFF time—equating to reductions of 10.1 hours on the UDysRS and 1.0 hour of OFF time. In comparison, the immediate-release/extended-release formulation showed more modest improvements of 13.3% and 1.4% (5.3-hour and 0.1-hour reductions), while the immediate-release formulation yielded improvements of 16.8% and 6.4% (5.8-hour and 0.4-hour reductions), respectively. These findings suggested the AMT-ER formulation provides a more robust and sustained effect on both dyskinesia severity and motor fluctuations.

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REFERENCES
1. Grall M, Crouse N, Formella AE, Zwick E, Moss H. Outcomes following initiation of amantadine DR/ER (Gocovri®) in patients with Parkinson disease: Evaluation of the AAN Axon registry database. Presented at: 2025 ATMRD Congress; June 27-30; Minneapolis, MN.z
2. Gocovri (amantadine extended release). Michael J. Fox Foundation for Parkinson’s Research. Accessed July 1, 2025. https://www.michaeljfox.org/news/gocovri-amantadine-extended-release
3. Oertel WH, Pahwa R, Hauser RA, Sale M, Went GT. Analysis of amantadine formulations for OFF and dyskinesia in Parkinson disease. Presented at: ATMRD Congress; June 17-19, 2022; Washington, DC.