(88) PROVE Study 506: Analysis of a Retrospective, Phase IV Study of Perampanel in Real-World Clinical Care of Patients Based on Seizure Type

Rationale: In the U.S., perampanel is approved for partial-onset seizures (POS; adjunctive and monotherapy) in patients aged ≥ 4 years, and adjunctive treatment of primary generalized tonic-clonic seizures in patients aged ≥ 12 years. There is limited information on real-world use of perampanel in patients with epilepsy in the US. PROVE (Study 506; NCT03208660) was a retrospective, multicenter, non-interventional Phase IV study of perampanel during real-world clinical care of patients with epilepsy in the US. We report real-world efficacy and safety of perampanel administered to patients with epilepsy during routine clinical care from PROVE, based on baseline seizure type.

Methods: Data were obtained retrospectively from medical records of patients with a diagnosis of epilepsy who initiated perampanel after January 1, 2014. Follow-up completed on March 15, 2019. Primary endpoint was retention rate (proportion of patients remaining on perampanel at 3, 6, 12, 18, and 24 months following treatment initiation; Safety Analysis Set [SAS]). Dosing, efficacy, and safety were secondary objectives. Outcomes were stratified by the most common baseline seizure types: POS only (with/without secondarily generalized seizures [SGS]), generalized seizures only (includes all generalized seizures; excludes patients with SGS), myoclonic seizures, and absence seizures. Some patients may have had multiple seizure types; however, due to substantial overlap between groups the current analyses only include patients who had seizures in either the POS only or generalized only groups and patients with mixed seizure types (n=718) are excluded.

Results: The SAS included 1703 patients (median [range] age, 26.0 [1­–84] years). Mean (standard deviation) maximum doses (mg/day) were: POS only (n=545), 6.9 (3.0); generalized only (n=440), 6.0 (3.1); myoclonic (n=328), 6.4 (3.2); and absence (n=301), 6.5 (3.3). Retention rates at 24 months by baseline seizure type were comparable (47.7% to 50.3%; Figure 1). Of 51 patients with available seizure data at Months 22–24 (Full Analysis Set), median reductions in total seizure frequency/28 days from baseline were 75.0% (POS only, n=20), 91.6% (generalized only, n=10), 70.0% (myoclonic, n=7), and 100.0% (absence, n=4). Fifty-percent responder rates were: POS only, 65.0% (n=13/20); generalized only, 70.0% (n=7/10); myoclonic, 57.1% (n=4/7); absence, 100.0% (n=4/4). Seizure-freedom rates were: POS only, 45.0% (n=9/20); generalized only, 30.0% (n=3/10); myoclonic, 14.3% (n=1/7); absence, 75.0% (n=3/4). As shown in Table 1, the incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to discontinuation were similar across subgroups. The most common TEAEs were dizziness and aggression (Table 1).

Conclusions: Dosing and retention rates on perampanel after 24 months were generally similar across seizure types. Seizure frequency reductions were observed across subgroups, and were highest for patients with absence or generalized seizures only. Safety profiles were similar across subgroups.

Funding: Please list any funding that was received in support of this abstract.:

Funding: Eisai Inc.
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