Long-Term Perampanel Efficacious Regardless of Enzyme-Inducing Anti-Seizure Medications

Data presented virtually at the American Epilepsy Society (AES) Annual Meeting, December 4–8, 2020, revealed that long-term adjunctive perampanel (Fycompa; Eisai) 4 mg/day is efficacious and generally well-tolerated in patients from Asia-Pacific with or without secondarily generalized seizures (SGS), regardless of enzyme-inducing anti-seizure medications (EIASMs).1

Presented by Lynn Kramer, MD, chief clinical officer and chief medical officer, Neurology Business Group, Eisai, the results showed a higher median percent reduction in seizure frequency per 28 days in patients receiving non-EIASMs compared with EIASMs for both partial-onset seizures (POS; median difference, 28.3; 95% CI, 3.7–54.8) and SGS (median difference, 16.2; 95% CI, –54.9 to 94.7).

All told, there was 85 patients (mean age, 34.6 years [standard deviation (SD); 13.55]; 58.8% female) who participated in the open-label extension phase of the Asia-Pacific Study 335 (NCT01618695) and received a modal dose perampanel 4 mg/day.

EIASMs used in the study included carbamazepine, phenytoin, and oxcarbazepine. In total, 48 (56.5%) of the patients included received concomitant EIASMs and 37 (43.5%) patients received non-EIASMs.

Patients included in the study presented with POS and were aged ≥12 years. The core study comprised 6-week pre-randomization and 19-week randomization (6-week titration; 13-week maintenance) periods, while the open-label extension was comprised of a 4-week pre-conversion, 6-week conversion, and at least 46-week maintenance periods.

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End points such as 50% responder rates were greater in the non-EIASMs group compared to the those with EIASMs for POS (relative risk, 4.9; 95% CI, 2.0–11.9). However, they were similar for SGS (relative risk, 0.8; 95% CI, 0.5–1.5).

Seizure freedom rates, another topline end point of the study, were found to be greater in the non-EIASM group versus EIASMs for both POS (2.7% [1 of 37] vs 0% [0 of 46]; relative risk data not available) and SGS (20% [n = 2 of 10] vs 6.3% [1 of 16]; relative risk, 3.9; 95% CI, 1.5–10.2).

In terms of safety, the rate of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs were slightly higher in the non-EIASM group (94.6%; 81.1%) compared to the EIASM group (85.4%; 72.9%). In contrast, the rate of serious TEAEs was higher in those with EIASMs (16.7%) compared to the non-EIASM patients (8.1%).

Dizziness was the most common AE, occurring in both the EIASM (45.8%) and non-EIASM (45.9%) groups, respectively. Other common AEs observed were somnolence, headache, nasopharyngitis, anxiety, convulsion, irritability, vertigo, aggression, suicidal ideation, and weight increase.

Kramer and colleagues concluded, “patients receiving perampanel in combination with an EIASM may require a higher perampanel dose to achieve similar efficacy with only non-EIASMs.”

Initially, perampanel was approved in 2012 as an adjunctive therapy for POS, and the indication was later expanded to include patients 12 years of age and older with primary generalized tonic-clonic seizures. In 2017, perampanel received a monotherapy indication for POS with or without SGS in those with epilepsy 12 years of age and older.

The FDA then expanded the indication of perampanel for monotherapy and adjunctive use in pediatric patients 4 years of age and older for the treatment of POS with or without SGS in September 2018. Notably, the approval included both tablet and oral suspension formulations.2

For more coverage of AES 2020, click here.

REFERENCES

1. Kramer LD, Nishida T, Dash A, Patten A, Ngo LY, Malhotra M. Long-term effect of concomitant enzyme-inducing anti-seizure medications (EIASMs) on the efficacy and safety of adjunctive perampanel 4 mg/day in patients with partial-onset seizures in study 335. Presented at AES 2020 Virtual Meeting; December 4–8, 2020; Abstract 768

2. Eisai Announces FDA Approval Of FYCOMPA in Pediatric Patients As Young As 4 Years Old For The Treatment Of Partial-Onset Seizures News release. Eisai Inc. September 28, 2018. Accessed December 10, 2020. https://www.prnewswire.com/news-releases/eisai-announces-fda-approval-of-fycompa-in-pediatric-patients-as-young-as-4-years-old-for-the-treatment-of-partial-onset-seizures-300721117.html.