Both Low- and High-Dose Perampanel Effective and Well-Tolerated

December 7, 2020
Victoria Johnson
Victoria Johnson

Victoria Johnson, Assistant Editor for NeurologyLive, joined the MJH Life Sciences team in October 2020. Follow her on Twitter @VictoriaJNeuro or email her at vjohnson@neurologylive.com

The data suggest that some patients with partial-onset seizures may benefit from lower doses to mitigate treatment emergent adverse events, but these must be tailored to each patient.

Data from a new post-hoc analysis presented at the American Epilepsy Society (AES) Annual Meeting, December 4–8, 2020, shows that both low (4 or 6 mg/day) and high (8, 10, or 12 mg/day) adjunctive perampanel maintenance doses resulted in seizure improvements in patients with partial-onset seizures (POS).1 (editor’s note: POS seizures are now officially referred to as focal-onset seizures.)

Study author Dae-Won Seo, MD, PhD, professor, department of neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, and colleagues performed this post-hoc analysis of the FAME study (Study 412, NCT02726074) to assess the safety and efficacy of adjunctive perampanel. The data presented by Seo showed that perampanel was well tolerated by patients who received both low and high doses.

In the full analysis set, Seo and colleagues analyzed data from 85 patients, 16 of which had secondarily generalized seizures (SGS). Out of all the patients with POS, 82.4% (n = 70) received low-dose perampanel and 17.6% (n = 15) received high-dose perampanel. The 16 patients with SGS received low-dose perampanel. 

Overall, the ≥50% responder rate was 88.6% (n = 62) for low-dose perampanel and 40% (n = 6) for high dose perampanel (P = .0002). Seizure freedom rate was 54.3% (n = 38) for low-dose and 13.3% (n = 15) for high-dose (P = .0039). During the maintenance period, POS frequency per 28 days was reduced by a median of 100% (n = 69) for low-dose and 16.7% (n = 15) for high-dose perampanel groups (P = .0001). In patients that had both POS and SGS, the 50% responder rate was 87.5% (n = 14) and the seizure-freedom rate was 75% (n = 12).

READ MORE: Perampanel Reports High Compliance and Good Tolerance in Phase 4

In the safety analysis set, Seo and colleagues analyzed data from 88 patients, 83% (n = 73) of which received low-dose perampanel, and 17% (n = 15) of which received high-dose perampanel. Of these patients, 73.9% (n = 65) reported treatment-emergent adverse events (TEAEs) such as dizziness, somnolence, and headache. TEAEs were more common in low-dose patients (76.7% vs. 60%) than high-dose patients, but the larger pool of low-dose patients made this an unreliable comparison, according to Seo et al. Some serious TEAEs did occur, 5 in low-dose patients and 1 in high-dose patients, and 4 patients discontinued due to a TEAE. One case of suicide attempt was reported with low-dose perampanel (4 mg/day) in a patient with no prior psychiatric history, but the TEAE was not considered related to perampanel.

“These results suggest that some patients may achieve seizure control with lower perampanel doses; however, others may require up-titration to a higher dose based on response. Interpretation of these data should consider the higher number of patients in the low- vs high-dose groups,” Seo and colleagues concluded.

The team presented additional data at AES 2020 that included multivariate analyses on the FAME study that found that longer total administration period, higher perampanel dose, and presence of a concomitant non-ASM were potential predictors of response to perampanel. Concomitant non-antiepileptic medication was also a significant predictor of seizure freedom (P = .0421). No epilepsy-specific or demographic variables were found to predict seizure reduction.2

For more coverage of AES 2020, click here.

REFERENCES
1.Seo DW, Lee JW, Dash A, Lee SK, Lee SA, Malhotra M. Efficacy and safety of low- and high-dose perampanel as first adjunctive therapy in patients with partial-onset seizures (pos): Post hoc analysis of the fame study. Presented at AES 2020 Annual Meeting; December 4–8, 2020. Abstract 771.
2.Lee JW, Kim DW, Seo DW, Dash A, Malhotra M. Clinical factors associated with response to perampanel as first adjunctive treatment in patients with partial-onset seizures in the FAME study. Presented at AES 2020 Annual Meeting; December 4–8, 2020. Abstract 769.