Q&A: Sublingual apomorphine more effective than levodopa for Parkinson’s off episodes

Apomorphine sublingual film resulted in greater motor improvement and an increase in responders at earlier time points compared with levodopa, according to results from a study of more than 300 patients with Parkinson’s disease.

Researchers presented the findings, which were consistent with previous research and further support the use of apomorphine sublingual film in patients with PD who have a delayed response in on time to levodopa, at the American Academy of Neurology annual meeting, which was held virtually.

Researchers analyzed motor improvements with apomorphine sublingual film vs. levodopa in patients with PD experiencing off episodes, according to the presentation. The trial comprised 384 patients with comparable Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III scores who received apomorphine sublingual film and levodopa.

Healio Neurology spoke with Jennifer S. Hui, MD, clinical associate professor of neurology at the University of Southern California’s Keck School of Medicine and director of the deep brain stimulation program at Keck Hospital, to learn more about the study results.

Healio Neurology: What prompted this research?

Hui: The current standard of care for PD includes the use of oral medication, including levodopa/carbidopa, often accompanied by adjunctive maintenance therapies. Off episodes — the re-emergence or worsening of PD symptoms otherwise controlled with oral levodopa/carbidopa — can be burdensome for people living with PD and their care partners and these episodes become more frequent as PD progresses.

Off episodes may occur in as many as 50% of people with PD with disease progression and after 5 years of levodopa treatment, and the percentage increases over time; 70% of patients will experience off episodes with disease progression and after 9 years of oral levodopa treatment.

Despite the prevalence and impact of off episodes, most medicines for PD off episodes focus on keeping people on vs. treating off episodes as they occur. Apomorphine sublingual film is the first and only FDA-approved sublingual therapy approved to treat off episodes associated with PD as they occur.

This pooled analysis of the pivotal and ongoing long-term safety studies — the open-label dose titration phases — and long-term studies compares motor responses after treatment with apomorphine sublingual film vs. levodopa in patients with PD off episodes.

Healio Neurology: What does prior research demonstrate about the efficacy of apomorphine sublingual film?

Hui: Phase 3 clinical trial results published in Lancet Neurology demonstrated that people with PD treated with apomorphine sublingual film experienced improvements in motor control (eg, improved ability to raise from a chair) at 30 minutes after dosing at week 12 compared with placebo, with numerical improvements seen as early as 15 minutes post-administration.

Interim data from an open-label phase 3 extension study presented at the International Parkinson and Movement Disorder Society Virtual Congress in 2020 supported apomorphine sublingual film’s long-term efficacy, safety and tolerability in up to 48 weeks of patient use, with results consistent with the 12-week study.

Healio Neurology: What did the study results demonstrate?

Hui: The pooled analysis shared at the AAN annual meeting found that the mean motor response with apomorphine sublingual film was approximately two times higher than with levodopa at 15 minutes post-dose (–13.9 vs. –6.7) and remained higher at 30 minutes (–22.9 vs. –16.3). More patients were responders (30% reduction in Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score vs. pre-dose) to apomorphine sublingual film compared with levodopa, respectively, at 15 minutes (52% vs. 21%) and 30 minutes (88% vs. 65%). In addition, responder rates were similar at 60 minutes (88% vs. 92%). The levodopa peak response occurred at 60 minutes (–24.3 vs –24.4).

The results of this pooled analysis were consistent with previous findings showing that apomorphine sublingual film was associated with greater motor improvement and more responders at earlier time points vs. levodopa, further supporting its use in people with PD with a delayed on response to levodopa.

Reference:

Hui J, et al. Motor responses to apomorphine sublingual film compared with levodopa in patients with Parkinson’s disease and “OFF” episodes. Presented at: American Academy of Neurology Annual Meeting; April 17-22, 2021 (virtual meeting).