Objective: Evaluate long-term safety (LTS), tolerability, and efficacy of apomorphine sublingual film (APL) for on-demand treatment of “OFF” episodes in patients with Parkinson’s disease (PD).

Background: In a 12-wk pivotal study, APL was efficacious and generally well tolerated for treatment of “OFF” episodes in PD.

Method: An ongoing, open-label, Phase 3 study (NCT02542696) enrolled patients with PD (new or rollover from prior studies) and “OFF” episodes while on stable PD medications. APL dose titration occurred in patients who were “OFF” to determine the effective and tolerable dose (10–35 mg; 5-mg increments) that converted them to FULL “ON” within 45 min. In the LTS phase, patients self-administered their titrated APL dose for up to 5 “OFF” episodes/d. Endpoints included TEAEs in the LTS phase (primary), change from predose in MDS-UPDRS Part III or Part IV score, percentage of patients with self-rated FULL “ON” within 30 min postdose at in-office visits or by home diary, and Clinical and Patient Global Impression of Improvement (CGI-I, PGI-I) at wks 24, 36, and 48.

Results: This analysis (data cut 30Sep2020) evaluated 397 patients who received ≥1 APL dose (40%, 24%, and 11% for >6, >12, and >24 mos) during the LTS phase; 65% of patients were titrated to FULL “ON” at 10–20 mg (most common: 15 mg). TEAEs occurred in 84% of patients, most (58%) were mild, and the most common (>5%) were nausea (21%), fall (8%), oral mucosal erythema (7%), somnolence (7%), dizziness, dyskinesia, fatigue, lip swelling, mouth ulceration, and yawning (6% each). TEAEs leading to discontinuation occurred in 35% of patients; the most common (>5%) was nausea (6%). Deaths occurred in 5 patients during the LTS phase; none were drug related. At wk 24, changes from predose in mean MDS-UPDRS Part III scores at 15, 30, and 60 min postdose were –13.9, –21.4, and –20.2 points, respectively. Similar results were observed at wks 36 and 48. Patient-rated FULL “ON” was observed in 76–83% of patients within 30 min postdose through 48 wks. The majority of patients demonstrated improved CGI-I (61–69%) and PGI-I (63–65%) responses, and the majority achieved FULL “ON” responses by home diary (81–89%) without troublesome dyskinesia through 48 wks.

Conclusion: Interim results up to 48 wks showed that repeated and chronic use of apomorphine sublingual film is well tolerated and effective as an on-demand treatment for “OFF” episodes in patients with PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/long-term-safety-and-efficacy-of-apomorphine-sublingual-film-for-off-episodes-in-parkinsons-disease/