Abstracts

This abstract has been invited to present during the Clinical Research platform session

Rationale: In the U.S. and EU, perampanel is approved for focal-onset seizures, with or without focal to bilateral tonic-clonic seizures (FBTCS), in patients aged ≥ 4 years (US, adjunctive and monotherapy; EU, adjunctive), and for adjunctive treatment of primary generalized tonic-clonic seizures (GTCS) in patients aged ≥ 12 years (EU, ≥ 7 years with idiopathic generalized epilepsy [IGE]). Data from prospective clinical studies with perampanel in Germany are limited due to a temporary absence from the market between 2013–2017, and reflect experiences mainly as late-line adjunctive therapy in complex drug regimens for refractory epilepsies prior to 2013. Additionally, perampanel was only approved in the EU for GTCS with IGE in 2015. Here, we report the first interim analysis results in PERPRISE (Study 509; NCT04202159), which evaluates the effectiveness of perampanel as the only adjunctive treatment in adults with FBTCS/GTCS in clinical practice in Germany.

Methods: PERPRISE is a multicenter, prospective, observational, Phase IV study. Patients aged ≥ 18 years with a confirmed diagnosis of FBTCS/GTCS due to focal epilepsy or IGE with ≥ 1 FBTCS or GTCS ≤ 3 months prior to inclusion, and who are receiving perampanel as the only adjunctive to anti-seizure medication (ASM) monotherapy or as a substitute for one ASM during dual therapy are eligible. Primary endpoint: 12-month retention rate; secondary endpoints include: 6-month retention rate, seizure freedom, and safety. The Interim Analysis Set (IAS) comprises the first 100 patients to receive ≥ 1 dose of perampanel and attend or discontinue prior to the 6-month visit.

Results: As of November 25, 2021, the IAS included 100 patients (n=43, adjunctive; n=55, substitution; n=2, missing). Disease characteristics and treatment history are in Table 1. The mean (standard deviation) last perampanel doses were 4.6 (1.8; adjunctive) and 6.3 (2.5; substitution) mg/day. Overall, the 6-month retention rate was 78.0% (95% confidence interval [CI] 68.6, 85.7); when stratified by group, these were 83.7% (95% CI 69.3, 93.2; adjunctive) and 72.7% (95% CI 59.0, 83.9; substitution). Seizure-freedom rates were 58.8% for FBTCS/GTCS (72.2%, adjunctive; 47.9%, substitution), 64.5% for FBTCS (77.8%, adjunctive; 52.9%, substitution), 41.4% for focal impaired awareness seizures (61.5%, adjunctive; 25.0%, substitution), and 56.5% for GTCS (55.6%, adjunctive; 57.1%, substitution). Seizure-freedom rates varied with treatment stage (Figure 1). The incidences of treatment-emergent adverse events (TEAEs) and serious TEAEs were 48.0% and 7.0%, respectively; TEAEs led to perampanel withdrawal in 16.0% of patients. The most common TEAEs were dizziness (9.0%), irritability (7.0%), fatigue (7.0%), and gait disturbance (5.0%).

Conclusions: Based on these data, perampanel as the only adjunctive treatment for adult patients with FBTCS/GTCS was retained by > 70% of patients after 6 months and was associated with high degrees of seizure freedom. Further data from PERPRISE will be of value to inform real-life clinical decision-making in this patient cohort.

Funding: Eisai GmbH