Recent findings from a post-hoc analysis of the phase 3 1601 study and its open-label extension (OLE) have illuminated the efficacy and safety of fenfluramine (marketed as Fintepla by UCB) for patients suffering from Lennox-Gastaut syndrome (LGS), regardless of concurrent use of vagus nerve stimulation (VNS). This news is particularly significant for families dealing with this debilitating condition, as the implications could lead to more tailored treatment strategies.

The original study was a rigorous 14-week randomized controlled trial that involved patients being assigned to doses of fenfluramine (0.2 mg/kg/day or 0.7 mg/kg/day, max 26 mg/day) or a placebo. The OLE, which followed, allowed for flexible dosing of fenfluramine while maintaining current VNS settings and concomitant antiseizure medications during the investigation period.

Under the guidance of Dr. Lieven Lagae, a respected pediatric neurology expert from the University of Leuven in Belgium, the results were telling. While the combination of fenfluramine and VNS initially appeared to lead to greater reductions in generalized tonic-clonic seizures (GTCS) during the RCT, follow-up data from the OLE indicated that patients administered fenfluramine alone actually saw higher median reductions in GTCS frequency.

In the initial RCT, patients receiving both treatments experienced median reductions of 69.6% (0.2 mg/kg/day) and 50.1% (0.7 mg/kg/day) in GTCS, compared to reductions of 57.0% and 41.2% for the groups without VNS. However, the OLE data painted a different picture, with patented reductions of 56.3% for those on fenfluramine alone versus 37.9% for patients using both treatments.

At the upcoming 2024 American Epilepsy Society (AES) Annual Meeting from December 6-10 in Los Angeles, this study will be a focal point. The original RCT included a diverse group: 82 patients were prescribed VNS (with 50 receiving fenfluramine and 32 on placebo), while 181 were treated without this concurrent therapy.

Interestingly, when examining the ability of patients to achieve significant seizure reduction—both at least a 50% and a 75% reduction—those who received only fenfluramine outperformed their counterparts on a combination treatment. Specifically, in the OLE phase, 32.9% of fenfluramine-only patients achieved a 50% reduction compared to only 27.5% of those using both medications.

From a safety perspective, fatigue emerged as a notable adverse effect; patients using both fenfluramine and VNS reported a higher incidence of this side effect compared to those treated without VNS.

Importantly, this study contributed to fenfluramine's approval for LGS in 2022, as published in JAMA Neurology. The research demonstrated a significant reduction in monthly drop seizure frequency, with notable differences between the fenfluramine and placebo groups.

In a groundbreaking change earlier this year, fenfluramine was removed from the Schedule IV controlled substance list, granting healthcare providers the ability to prescribe it for a full year instead of the previous six-month limitation—a game changer for ongoing patient care.

This body of research offers hope for countless families who are struggling with the daunting challenges posed by Lennox-Gastaut syndrome. Further investigations will continue, offering a deeper understanding of the complexities of managing LGS and the impact of different treatment combinations.

Stay tuned for more groundbreaking updates from the 2024 AES Annual Meeting!