Long Term Safety and Efficacy of Sublingual Apomorphine for Parkinson Disease

In an ongoing, open-label phase 3 study (NCT02542696) of apomorphine sublingual film (APL) (Kynmobi; Sunovion, Marlborough, MA) for treatment of OFF episodes in Parkinson disease (PD) 88% of participants were able to reach an effective tolerable dose with using antinausea medications. Participants were both those from prior APL studies and without previous exposure to APLwho had “OFF” episodes while on stable treatment with PD medications. 

This analysis evaluated 176 new participants who received ≥1 dose of APL during the dose-titration (DT) phase; 31 (18%) used concomitant trimethobenzamide (TMB) and 145 (82%) did not. The median duration of TMB use during the DT phase was 16 (1–50) days. Nausea was reported in 52% of participants who received TMB versus 13% in those who did not. Nausea or vomiting was reported in 55% of participants who received TMB vs 13% in those who did not. 

In another study of 397 indviduals, regular long-term use of APL was well tolerated and effective as an on-demand treatment for “OFF” episodes in individuals with PD. Titration (10–35 mg; 5-mg increments) occurred to determine the effective and tolerable dose for an individual that converted them to FULL “ON” within 45 min. Full ON occurred at a dose of 10 to 20 mg APL for 65% of participants s who received  at least 1 APL dose with 40% of patients using APL for at least 6 months, 24 % for over 12 months, and 11% for over 24 months. APL as an on-demand treatment for “OFF” episodes in participants with PD had minimal impact on impulse control disorders (ICDs) during a period of 48 weeks in this long-term study.

“These data provide a deeper understanding of the patient treatment experience and reinforce the previously-reported tolerability of Kynmobi for the on-demand treatment of PD OFF episodes,” said William G. Ondo, MD, professor of Neurology and director of the Movement Disorders Clinic at Methodist Neurological Institute in Houston, Texas, and CTH-301 study investigator. “Acute nausea was more commonly reported by patients who were not taking a maintenance dopamine agonist at baseline. The experience of acute nausea in Kynmobi trials was largely mild in nature and rarely impacted successful titration or treatment continuity, even in the absence of antiemetic treatment.”

Treatment emergent adverse events (TEAEs) occurred in 84% of participants; the most common were dizziness, dyskinesia, fatigue, lip swelling, mouth ulceration, and yawning (6% each), fall (8%), nausea (21%), oral mucosal erythema (7%), somnolence (7%). The most common (>5%) TEAE leading to discontinuation occurring in 35% of participants was nausea (6%).

These data were presented at the International Parkinson and Movement Disorder Society (MDS) Congress 2021.