Continuous subcutaneous apomorphine infusion reduces motor fluctuations in PD

Key takeaways:

• 52-week study included 85 adults with Parkinson’s and at least 3 hours/day of “off” time.
• At week 12, CSAI led to sustained reduction in “off” time with an increase in “on” time without troublesome dyskinesia.

CHICAGO — Continuous subcutaneous apomorphine infusion reduced “off” time and increased “on” time without troublesome dyskinesia in patients with Parkinson’s disease in the United States, with no new safety signals reported.

“Parkinson’s patients, as they progress with their oral therapies and their disease, ultimately continue to have ‘off’ time and ‘off’ episodes, and it becomes more challenging to thread the needle into that narrowing therapeutic window,” Nikkilina Crouse, PhD, director of medical affairs at Supernus Pharmaceuticals, told Healio during a poster presentation at the International Association of Parkinsonism and Related Disorders World Congress.

Lead study author Stuart H. Isaacson, MD, and colleagues sought to evaluate long-term safety and efficacy of continuous subcutaneous apomorphine infusion (CSAI) for those with motor fluctuations in PD treated in the United States, as the treatment has been used in Europe for nearly three decades and confirmed by the TOLEDO open-label extension study.

They conducted a phase 3, open-label study over 52 weeks in 18 U.S. centers and included 99 adults diagnosed with advanced idiopathic PD. Eligible participants were required to have at least 3 hours per day of “off” time and unable to achieve sufficient motor control after administration of levodopa and at least one other adjunctive treatment.

Participants underwent a titration period across four to six clinic visits, in which CSAI was initiated with a 1 mg to 2 mg bolus at an infusion rate of 1 mg per hour, and titrated in 0.5 mg to 1 mg per hour increments to a maximum of 8 mg per hour. Patients then entered the 52-week maintenance phase (1-8 mg per hour with up to three boluses), with medication adjustments only to reduce adverse events or troublesome dyskinesia.

Primary safety endpoints included adverse events and assessments on the Epworth Sleepiness Scale (ESS), Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s disease Rating (QUIP-RS) and Columbia Suicide Severity Rating Scale (CSS). The primary efficacy endpoint was reduction of “off” time at week 12 as recorded by participants, while secondary endpoints at week 12 included “on” time without troublesome dyskinesia, “off” time reduction of at least 2 hours and Patient Global Impression of Change.

According to results, 85 individuals progressed past initial titration with 48 completing the maintenance phase and 45 entering treatment extension. The mean infusion rate from week 1 to week 12 was 3.6 mg per hour.

Researchers reported similar findings to the TOLEDO study, as CSAI reduced “off” time by approximately 3 hours with a similar increase in “on” time without troublesome dyskinesia. While no new safety signals were observed and most adverse events were mild to moderate, 78% of participants experienced skin reactions at the infusion site but none were severe. Further, nearly 90% of participants reported improvement with CSAI treatment.

“What we found was [our data] very much mirrored the TOLEDO data in terms of safety, so we identified no new safety signals, and the efficacy mirrors what we saw in the TOLEDO study as well,” Crouse told Healio.