FAME Study: Partial-Onset Seizures
EP: 1.Phase 4 ELEVATE Study
EP: 2.Clinical Benefit of Fenfluramine in Dravet Syndrome
EP: 3.Safety and Efficacy of CBD in Patients With TSC
EP: 4.ELEKTRA Study in Dravet and Lennox-Gastaut Syndromes
EP: 5.Focal Seizures: Post-hoc Analysis of Cenobamate
EP: 6.FAME Study: Partial-Onset Seizures
EP: 7.BELIEVE Trial: Developmental and Epileptic Encephalopathies
EP: 8.Interim Analysis of Diazepam Nasal Spray in Epilepsy
EP: 9.Using Midazolam Nasal Spray for Seizure Clusters
EP: 10.QoL of Cenobamate in Treatment-Resistant Epilepsy
Amit Verma, MD, reviews the safety and efficacy of low-dose and high-dose perampanel as first adjunctive therapy in patients with partial-onset seizures as seen in the post hoc analysis of the FAME study.
Amit Verma, MD: The FAME study was done with perampanel. The brand name is Fycompa. Fycompa is indicated for partial-onset seizures. Initially, it was approved for adjunctive therapy. Subsequently, it got an approval in monotherapy. Even though it’s been available for many years, there are still many physicians who are somewhat concerned about using it early on in treatment. A lot of physicians, especially in the community, still tend to use it later in the course of their regimen. They might use it as the third, fourth, or fifth add-on.
The FAME study was designed to assess the safety and efficacy of Fycompa after patients failed their first medication. This would be much earlier in the course of a patient’s treatment. They had patients start at 2 mg, and then their dose was titrated up over a course of 12 weeks to a maximum of 12 mg. The patients were divided into 2 categories: low dose vs high dose. Low dose was considered to be 4 or 6 mg, and high dose was considered to be 8, 10, and 12 mg. There was a 24-week maintenance phase during which the efficacy of the medication was assessed.
The first thing they found was that most of the patients were on the low doses, 4 and 6 mg, during the trial. There was also a significant difference in efficacy between the 2 groups. In the low-dose group, about 88% patients had a greater than 50% reduction in their seizures vs 50% or so for the patients in the high-dose group who were taking 8-, 10-, or 12-mg doses. The overall safety profile was good, in terms of treatment-emergent adverse effects. The most common adverse effects were sleepiness, dizziness, and somnolence.
This study showed that oftentimes, you can achieve efficacy with perampanel at low doses—4 or 6 mg. You don’t have to titrate them up to the 8-, 10-, or 12-mg doses. That certainly that helps in a couple of ways. No. 1, It can help reduce the overall adverse-effect profile that the patient might experience. It also lets you achieve effective doses much sooner. If the perampanel has a half-life of about 105 hours, and you start someone at 2 mg, you can get them up to 4 mg within 2 weeks. If you want to aim for the 8-, 10-, and 12-mg doses, it’s going to take a much longer period of time to get to a baseline dose. You can get good efficacy at low doses, based on the FAME trial. They saw good efficacy, even when it was used as the first adjunctive medication following a first initial monotherapy failure.
The real-world significance is that it’s quite an efficacious medication early on. The FAME study assessed the first add-on medication. The efficacy was good at low doses. You don’t have to get up to the high doses to see efficacy. The advantage is that typically, when we’re titrating Fycompa, we increase the dose by 2 mg about every 2 weeks. The reason is because it has a long half-life of about 105 hours. Some people are concerned that it might take a long time to reach efficacious doses. If you start at 2 mg and that’s an effective dose, and if 4 mg is an effective dose, then you can reach that dose within 2 weeks of starting the medication. You don’t necessarily have to wait a long time to see efficacy with this medication. In most clinical practices, once someone fails their first medication, the concern is that the patient is going to go on to be medically intractable. In that case, it’s going to be really difficult to control their seizures. With this medication, even at low doses of 4 to 6 mg, they saw good efficacy.
