UCB, a global biopharmaceutical company, on Monday announced that FINTEPLA (fenfluramine) oral solution CIV has been approved in the United States, by the U.S. Food and Drug Administration (FDA) for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients two years of age and older.
Additionally, the FDA has granted pediatric exclusivity for the product. It is already approved for the treatment of seizures associated with Dravet syndrome in patients two years of age and older in the US and EU.
Fenfluramine for LGS is available in the US through a restricted distribution program, called the Risk Evaluation and Mitigation Strategy (REMS) Program.
Lennox–Gastaut syndrome is a complex, rare, and severe childhood-onset epilepsy. It is characterized by multiple and concurrent seizure types, cognitive dysfunction, and slow spike waves on electroencephalogram (EEG). Typically, it presents in children aged 3–5 years and can persist into adulthood. It has been associated with several gene mutations, perinatal injuries, congenital infections, brain tumors/malformations, and genetic disorders such as tuberous sclerosis and West syndrome. The prognosis for LGS is poor, additionally, sudden unexpected death in epilepsy is a major concern for people living with LGS.
LGS affects an estimated 30,000 – 50,000 patients in the U.S.
Fenfluramine has demonstrated efficacy in the most difficult to treat seizure types, including drop seizures, which cause a person to suddenly lose muscle tone, become limp, and fall to the ground with a high likelihood of injury. Fenfluramine has a mechanism of action different from and complementary to current seizure medications, and it can be used with no disruptions to current antiseizure regimens. In the global placebo-controlled phase clinical trial, there were numerically greater improvements on the Clinical Global Impression scale (CG-I) in patients living with LGS when taking fenfluramine.
Kelly Knupp, M.D., MSCS, FAES, Associate Professor, Children’s Hospital Colorado, USA, said:
LGS is one of the most challenging epileptic encephalopathies to treat, and the vast majority of patients are not well controlled, despite a regimen of multiple antiepileptic drugs. As a complementary therapy, fenfluramine offers a different mechanism of action and demonstrated THE ability to significantly reduce the number of seizures associated with a drop, a critical measure for managing this severe form of epilepsy.
The FDA approval was supported by safety and efficacy data from a global, randomized, placebo-controlled Phase 3 clinical trial in 263 patients with LGS (age 2-35 years), which demonstrated that fenfluramine at a dose of 0.7/mg/kg/day significantly reduced the frequency of drop seizures compared to placebo (p=0.0037).
Dr. Tracy Dixon-Salazar, Executive Director of the Lennox-Gastaut Syndrome Foundation and mother to an adult daughter with LGS, said:
LGS is a severe, life-long disease with wide-ranging effects beyond seizures. It impacts every aspect of daily life and puts great strain on the entire family. There is a desperate need for more effective treatment options. The potential for fenfluramine to make a difference in the daily, horrific seizures we are dealing with in LGS CAN NOT be understated. We are so grateful for the researchers who have worked so hard to help all of us suffering at the hands of LGS.
UCB acquired Zogenix and fenfluramine on March 7, 2022. The acquisition is consistent with UCB’s sustainable patient value strategy and continued commitment to providing world-leading patient value to all people living with epilepsy, with an increasing focus on creating value and new solutions that address the unmet needs of people with certain specialized or rare types of epilepsy, where few or no options exist.