Objective: Assess impact of apomorphine sublingual film (APL-130277; APL) on time spent with and functional impact of dyskinesia among patients with Parkinson’s disease (PD) and “OFF” episodes.

Background: In a pivotal controlled (PC) study, APL significantly improved MDS-UPDRS Part III score at wk 12 vs placebo (LSM difference, –7.6; P=0.0002). However, dopaminergic agents have been associated with dyskinesia.

Method: Patients with PD and “OFF” episodes on stable PD medications (eg, oral/transdermal dopamine agonists) were enrolled in the PC (NCT02469090) and/or ongoing long-term safety (LTS; NCT02542696) study. Patients in a practically defined “OFF” state received APL (optimized dose [10–35 mg] that resulted in a FULL “ON” within 45 min determined during open-label titration) or matching placebo for 12 wks (PC study), or APL (optimized as before) for ≤48 wks (LTS study). Dyskinesia was assessed using MDS-UPDRS Part IV. Results were summarized descriptively and assessed at wk 12 (PC study, maintenance phase) and wks 24, 36, and 48 (LTS study, data cut May 2019). TEAEs were also collected.

Results: Analysis populations included 109 patients in the PC study (APL, n=54 [2.2 mean doses/d; 10/15/20/25/30/35 mg: 13%/33%/13%/22%/7%/11%]; placebo, n=55 [2.5 doses/d; 10/15/20/25/30/35 mg: 24%/20%/29%/16%/9%/2%]) and 345 in the LTS study (1.8 doses/d; 10/15/20/25/30/35 mg: 18%/25%/23%/16%/10%/8%). In the PC study, mean (SD) percent time with dyskinesia at wk 12 decreased with APL and increased with placebo (–2.82% [13.26] vs +5.95% [16.34]). APL resulted in less worsening of dyskinesia (12% vs 25% with placebo). More APL-treated patients reported “Improved” vs “Worsened” for time spent with dyskinesia (15% vs 12% with placebo). In the LTS study, more patients at wk 24 reported “Improved”/“No change” vs “Worsening” for change from baseline in time spent with (19%/65% vs 16%) and functional impact of (18%/65% vs 17%) dyskinesia; results were similar at wks 36 and 48. TEAEs of dyskinesia were not reported in the PC study and occurred in 7% (28/425) of patients in the LTS study, with no apparent dose relationship.

Conclusion: Apomorphine sublingual film as an on-demand treatment of “OFF” episodes in patients with PD resulted in reduced time spent with dyskinesia at 12 wks vs placebo (PC study) and higher rates of “Improved”/“No change” vs “Worsening” dyskinesia for up to 48 wks (LTS study).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/apomorphine-sublingual-film-for-on-demand-treatment-of-off-episodes-in-patients-with-parkinsons-disease-impact-on-dyskinesia/