Objective: Conduct a matching-adjusted indirect comparison (MAIC) of the efficacy of apomorphine sublingual film (APL) vs levodopa inhalation powder (CVT-301) for “OFF” episodes in Parkinson’s disease (PD).

Background: APL and CVT-301 are approved for the treatment of “OFF” episodes in PD. To date, no head-to-head trials have compared these treatments directly. MAICs can be used to evaluate efficacy between treatments in the absence of direct comparisons.

Method: An initial feasibility assessment determined that data from the Phase 3 trials of APL (CTH-300) and CVT-301 (SPAN-PD) were suitable for an MAIC. Raw or derived individual patient data (IPD) from CTH-300 (APL and placebo [PBO]) and summary statistics from SPAN-PD (CVT-301 84 mg and PBO) were analyzed. IPD from CTH-300 were selected using eligibility criteria from SPAN-PD, such that evaluable patients would have been qualified to enroll in the comparator trial. Efficacy outcomes were change from predose in UPDRS/MDS-UPDRS Part III score (MDS-UPDRS converted to UPDRS using a validated method) and reduction in total daily “OFF” time (estimated by patient-reported “OFF”/FULL “ON” status at discrete timepoints between 0-90 min postdose for APL; based on home diary entries for CVT-301) at wk 12. Outcomes were anchored by the PBO arms of each trial, and comparisons were conducted using Wald tests.

Results: The analysis evaluated 44 and 37 patients treated with APL and PBO (CTH-300), and 114 and 112 patients treated with CVT-301 and PBO (SPAN-PD), respectively. There were no statistical differences in adjusted change from predose in UPDRS Part III score at wk 12 between treatments at earlier time points (ie, 15–20 min and 30 min postdose), but the least squares (LS) mean difference was numerically favorable towards APL vs CVT-301 at 30 min postdose (–8.38 vs –3.92). At 60 min postdose, APL demonstrated a statistically significant improvement vs CVT-301 (–13.72 vs –4.90; P=0.002). The reduction in total daily “OFF” time at wk 12 was significantly larger for APL vs CVT-301 (adjusted LS difference, –1.32 h vs –0.01 h; P=0.013).

Conclusion: This MAIC enabled a statistically robust comparison of efficacy outcomes between APL and CVT-301. Results demonstrated numerically favorable improvement in motor function at 30 min postdose and significant improvement at 60 min postdose, and a significant reduction in daily “OFF” time with APL vs CVT-301.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/indirect-comparison-of-apomorphine-sublingual-film-versus-levodopa-inhalation-powder-for-off-episodes-in-parkinsons-disease/