In a PROVE study subgroup of adolescent patients exposed to perampanel over a 2-year period, the Eisai product proved to be well-tolerated and efficacious, with good retention rates.
Patricia E. Penovich, MD
The results of subgroup analysis from the PROVE study (Study 506) suggest that in real-world use, perampanel (Fycompa; Eisai) displays favorable retention rates and sustained efficacy for adolescents during routine clinical care, while also being well-tolerated.1
PROVE’s study period was 24 months, and in that time, perampanel use resulted in improvements in seizures for more than half of the study cohort of patients aged 12 to 18 years, with 53.5% (91 of 170) patients remaining on the therapy after the 2 years of clinical care. In total, 51.4% (n = 128) of patients had their seizures improve, 36.5% (n = 91) experienced no change or stable seizures, and 12% (n = 30) worsened.
The data were presented alongside additional subgroup analysis at the 73rd annual meeting of the American Epilepsy Society (AES), December 6-10, 2019, in Baltimore, Maryland.
“In real-world use, when employing either recommended or slower titration rates, we had a fewer percentage of side effects with similar and maintained efficacy,” study author Patricia E. Penovich, MD, neurologist, Minnesota Epilepsy Group, told NeurologyLive. “There’s a poster for those younger than 4 years old being treated off-label—a very small number—one for those treated on-label aged 4 to 12, one for those aged 12 to 18—this group—and then there’s also a poster that’s the whole study results altogether. They all jive in what they’re saying from the standpoint of the retention rates being actually quite good, with good efficacy.”
Retention rates for the full study cohort remained above 50% for the entirety of the study, starting at 79.2% (232 of 293 patients) at 3 months post-treatment initiation, and then dropping slightly at months 6, 12, and 18 to 69.1% (199 of 288), 59.9% (157 of 262), and 54.9% (117 of 213), respectively, before levelling off at 53.5% (91 of 170) by month 24.
Overall, the study population reduced in size, with 44.9% (n = 132) discontinuing due to a number of reasons: adverse events (AEs; 20.7%, n = 61), inadequate efficacy (14.6%, n = 43), patient choice (2%, n = 6), and other reasons (3.1%, n = 9). Additionally, 13 patients (4.4%) discontinued for unknown reasons.
“Some people didn’t enter the study in April of 2014, they may have entered in January of 2017,” Penovich explained. “In part, that’s why some of these numbers decrease over time because people were not exposed for that long. There were some people who dropped out for other reasons, and that’s another reason why that decreased over time.”
The cohort consisted of patients with varying seizure types, including partial onset (n = 112; 38.1%), idiopathic generalized epilepsy (n = 54; 18.4%), other (n = 85; 28.9%), and unknown (n = 43; 14.6%).
All told, during the 2-year period, 89.8% (n = 264) of patients were exposed to perampanel for >1 month, 67.7% (n = 199) for >6 months, 53.4% (n = 157) for >12 months, 39.5% (n = 116) for >18 months, and 31% (n = 91) for >24 months.
Notably, the maximum dose of perampanel used was lower than what was used in the randomized, controlled clinical trials. While 24.8% (n = 73) of patients utilized the standard 8 mg dose and 20.3% (n = 60) had a maximum dose of ≥10 mg, a large number of patients—54.3% (n = 160)—were exposed to a maximum dose of ≤7 mg. Of that group, 20.4% (n = 60) had a maximum dose of 6 mg, 19.7% (n = 58) had a maximum dose of 4 mg, and 11.9% (n = 35) had a maximum dose of 2 mg.
“If you read the package insert when you talk about doses, it’s 8 mg because that’s what the study said, and then you could go up to 12 mg,” Penovich said. “But the modal dose here with the adolescents is about 6 to 7 mg. A lot of patients got their efficacy at lower doses.”
As for safety, 38.4% of patients (n = 113) reported treatment-emergent AEs, with 31.3% (n = 92) having an AE which resulted in perampanel dose adjustment (withdrawal: 66 [22.4%]; reduction: 24 [8.2%]; increase: 1 [0.3%]; interruption: 5 [1.7%]). The most common AEs were aggression (n = 19; 6.5%), somnolence (n = 18; 6.1%), dizziness (n = 14; 4.8%), and seizure (n = 10; 3.4%).
“These numbers in general, for the [adverse] effects, are less than what you see on the package insert for the first titration-controlled study,” Penovich noted. In the clinical trials, those with partial-onset seizures experienced aggression, somnolence, and dizziness at average rates of 2%, 11%, and 30.3%, respectively, across doses of 4, 8, and 12 mg. In patients with idiopathic generalized epilepsy, the respective rates of somnolence, dizziness, and irritability were 11%, 32%, and 11% with the 8 mg dose.2
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1. Penovich P, Segal E, Patten A, Malhotra M. PROVE Study 506: Retrospective, Phase IV Study of Perampanel in Real-World Clinical Care of Patients Aged 12 to <18 Years with Epilepsy. Presented at: American Epilepsy Society 2019 Meeting. December 6-10, 2019; Baltimore, Maryland. Abstract 2.209.
2. Fycompa prescribing information [FDA label]. Fycompa website. Revised May 2019. fycompa.com/-/media/Files/Fycompa/Fycompa_Prescribing_Information.pdf Accessed December 8, 2019.