Fenfluramine was originally approved as a therapy for Dravet syndrome in 2020, and later gained expanded indication for Lennox-Gastaut syndrome in 2022.
Originally marked as a Schedule IV controlled substance, the DEA has published its final ruling on fenfluramine (Fintepla; UCB Pharma) stating that the oral medication is no longer subject to the Controlled Substances Act (CSA). Following receipt of this DEA rule, UCB has filed a labeling supplement with the FDA to remove Schedule IV designation from the medication.1
Fenfluramine, an antiseizure medication, originally received FDA-approval as a therapy for Dravet syndrome in patients aged 2 years and older in 2020, and later for the treatment of Lennox-Gastuat syndrome in March 2022. With the new ruling, most prescribers will be able to write a prescription for a full year’s supply versus the current limitation of 6 months. Prescribers will also now have the option to send a prescription to pharmacies electronically.
"We are pleased that FINTEPLA, which has a unique mechanism of action different from and complementary to other anti-seizure medications, has been descheduled and can help even more patients and families living with Dravet syndrome and Lennox-Gastaut syndrome manage the impact and burden of seizures," Brad Chapman, head, US Epilepsy and Rare Syndromes, UCB, said in a statement.1 "Physicians will now have the option to issue an electronic prescription for FINTEPLA rather than requiring patients to obtain a written prescription to access this important therapy, which may be simpler and a better experience for all involved."
Schedule IV drugs, substances, or chemicals are defined as drugs with a low potential for abuse and a low risk of dependence. Other examples of these drugs include Xanax, Soma, Darvon, Darvocet, Valium, Ativan, Talwin, Ambien, and Tramadol. In its labeling, fenfluramine has been noted to cause some serious adverse events, including valvular heart disease and pulmonary arterial hypertension. Echocardiograms are taken prior to fenfluramine initiation, again every 6 months during treatment, and 1 time 3-6 months after the last dose of fenfluramine.
The therapy also has boxed labeling about potential decreased appetite and weight, as well as increased sleepiness, sedation, and lack of energy. Like all other antiepileptic drugs, fenfluramine may cause suicidal thoughts or actions, although rare. Fenfluramine should not be prescribed to those who may be allergic to any of the ingredients of the therapy, and for those who are taking or have stopped taking monoamine oxidase inhibitors in the previous 14 days as this might cause serotonin syndrome.
"It is vitally important that our patient community has easy access to medicines that potentially reduce life-threatening and deadly seizures,” Mary Anne Meskis, executive director, Dravet Syndrome Foundation, said in a statement.1 “We are pleased to hear of the descheduling of FINTEPLA, which will remove roadblocks to access and ease caregiver burden."
In March 2022, the FDA expanded the indication of fenfluramine to include patients with LGS based on positive findings from the phase 3 Study 1601 (NCT03355209).2 In that study, fenfluramine-treated patients in the 7 mg/kg/day dose group achieved a –19.9% estimated median difference from placebo in monthly drop seizure frequency change from baseline, which was comparable to the magnitude demonstrated in all other LGS randomized controlled trials (range, –14.8% to –21.6%). Fenfluramine also showed statistically significant effects on secondary end points, including proportion of patients with a clinically meaningful reduction, defined as at least 50% in MDSF, which occurred in 25.3% of patients on fenfluramine compared with 10.3% on placebo (P = .0165).3
At the 2021 American Academy of Neurology (AAN) annual meeting, an analysis of fenfluramine showed that it improves everyday executive function in patients with LGS. They assessed this using the Behavior Rating Inventory of Executive Function (BRIEF) scale throughout a 14-week study period. After completion of both baseline and end of-study BRIEF assessments, researchers mapped the BRIEF ratings to the current BRIEF 2 parent form, a shorter, 63-item version that incorporated a 1400 sample normative population and statistics to support interpretation.4
Patients with LGS between 6 to 18 years old showed improvements in each of the 4 BRIEF 2 indexes following treatment with fenfluramine (n = 92) compared to placebo (n = 45). More specifically, for the fenfluramine group, there was a 24% improvement in Behavior (placebo, 13%; P = .118), 19% improvement in Emotions (placebo, 16%; P = .665), 27% improvement in Cognition (placebo, 13%; P = .665), and 25% improvement in Global Executive Composite (GEC) overarching summary score (placebo, 11%; P = .034).