Fenfluramine Safe and Effective for Treatment of Seizures in Lennox-Gastaut Syndrome

As published in JAMA, in a clinical trial (NCT03355209), participants with Lennox-Gastaut syndrome (LGS), who were mean age 13 years, were treated with fenfluramine (Fintepla, Zogenix, Emeryville, CA) or placebo. Approval for the expanded indication of fenfluramine to treat seizures in LGS was supported by these data. 

The median drop seizure frequency change was -26.5% in those treated with 0.7 mg/kg/day fenfluramine, compared with a -7.6% change in those treated with placebo. The estimated median difference between 0.7 mg/kg/day fenfluramine and placebo was −19.9% (95% CI, −31.0% to −8.7%; P = .001) fewer drop seizures per 28-day period. During the maintenance phase, the difference in median drop seizure frequency seen with fenfluramine vs placebo was similar to the overall study (−20.3; 95% CI, −31.6% to −8.9%; P = .002).

"Our trial data and the clinical evidence demonstrates the safety and efficacy of fenfluramine in LGS and especially for patients where generalized tonic-clonic seizures are the predominant seizure type, where there is a greater risk of mortality," said Kelly Knupp, MD, MSCS, FAES, associate professor, Children's Hospital Colorado, Principal Investigator of the study. "LGS is a highly treatment-resistant developmental and epileptic encephalopathy, and we need differentiated treatment options, such as fenfluramine, which has a unique mechanism of action different from and complementary to current antiseizure medications."

The study also included a seizure-type subgroup analyses that demonstrated that fenfluramine 0.7 mg/kg/day was highly effective in reducing the frequency of focal-to-bilateral tonic-clonic seizures (also known as generalized tonic-clonic seizures [GTC]) in nearly 50% of participants.

The most common treatment-emergent adverse events included decreased appetite, somnolence, and fatigue.