Fintepla Successfully Managed Patient’s Hard-to-treat Seizures
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Fintepla (fenfluramine) successfully managed the severe and difficult-to-treat seizures of a 20-year-old woman with Dravet syndrome, demonstrating the medication’s potential in real-life for treating such challenging cases, according to researchers.
“The profound and sustained response to [Fintepla] seen in this patient is similar to that observed in double-blind clinical trials,” the investigators wrote.
The case report, titled “Fenfluramine in the successful treatment of super-refractory status epilepticus in a patient with Dravet syndrome,” was published in the journal Epilepsy & Behavior Reports.
The patient, a woman in California, arrived at Hoag Memorial Hospital Presbyterian, in Newport Beach, in super-refractory status epilepticus or SRSE, which is an epileptic seizure that cannot be controlled within 24 hours of a third-line (or third type) of therapy, or that returns after going off such a therapy. Often, therapy consists of a continuous infusion of pentobarbital, propofol, or midazolam — all medications used as sedatives prior to surgery.
SRSE presents a significant clinical challenge and is associated with a mortality rate of approximately 33%.
The woman was admitted in November 2018, prior to Fintepla’s regulatory approval in 2020 in both the U.S. and Europe.
Developed by Zogenix, Fintepla is a low-dose solution of fenfluramine hydrochloride that is taken with other anti-epileptic treatments to reduce the frequency of seizures.
This patient had a history of status epilepticus seizures, having first been treated at Hoag in May of 2015, at age 17. Her therapeutic regimen at that time included phenobarbital, valproic acid, and Onfi (clobazam), an anticonvulsant therapy.
Additionally, the woman had been treated with vagus nerve stimulation (VNS) and was on a ketogenic diet — a high-fat, low-carbohydrate, and limited protein diet that has been used as a therapy for epileptic disorders since the 1920s.
Following a two-week hospitalization at another facility for a parainfluenza respiratory infection, the woman arrived at Hoag showing a “dramatic increase in seizure activity,” involving a buildup of water between the layers of tissue surrounding the lungs, or what is known as a pleural effusion.
Her seizures featured eye-opening, head jerks, and the lifting of the upper body approximately every 2-6 minutes, indicative of status epilepticus. The medical team started her on intravenous (into-the-vein) Ativan (lorazepam) at a dose of 4 mg, followed by intubation, in which a tube was inserted down her throat to help her to breathe.
At that point, the patient was transferred to the neurological intensive care unit (neuro ICU) for continuous monitoring, and was given intravenous propofol and midazolam.
These and other treatments, including pentobarbital, Epidiolex (cannabidiol), and ketamine, were administered over the next five weeks, along with adjustments to her VNS therapy.
However, all of these measures failed to control her SRSE, prompting her physicians to seek emergency approval from the U.S. Food and Drug Administration to use Fintepla — at that time still an experimental therapy.
“We believe the present case is the first reported case of fenfluramine used for treatment of tonic SRSE,” the investigators wrote.
Fintepla was given at a dose of 0.4 mg/kg/day and Epidiolex was discontinued on day 36 (just over a month later).
Doctors increased the Fintepla dose to 0.7 mg/kg/day after one week after failing to see any significant changes in the woman’s condition. One week after this, her seizures began to resolve, as measured both clinically and by electroencephalography, a measurement of electrical activity throughout the brain.
At the higher dose, the patient’s response “was rapid and dramatic,” the researchers wrote.
By day 55, the woman was declared seizure-free and was off all anesthetic treatments, although she remained on Fintepla as an add-on therapy to other medications.
The patient underwent two months of inpatient rehabilitation and has shown a lasting improvement in seizure control following discharge. She continues to take Fintepla and has reported no waking seizures, two to three brief tonic seizures — those featuring sudden stiffening and twitching — and, as of February 2021, a single tonic-clonic seizure, which is similar to a tonic seizure but with loss of consciousness.
Additional antiseizure medications given the patient include Depacon (sodium valproate), Briviact (brivaracetam), phenobarbital, Onfi, and levocarnitine (sold as Carnitor and Biocarnitine SF). The woman also continues to undergo rapid cycle VNS and maintains a ketogenic diet.
Also importantly, according to the researchers, the woman’s “neurocognitive status has significantly improved” following treatment.
“She is more alert and interactive, and her vocabulary and communication skills have significantly improved,” they wrote.
More research should be done to establish a maximum dose of Fintepla for treating SRSE in Dravet patients, according to the investigators. But they concluded that their report “illustrates the potential for fenfluramine to prevent reoccurrence of status epilepticus and to manage super-refractory status epilepticus in patients with Dravet syndrome.”
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