Fenfluramine Approved for Seizures in Patients Aged ≥2 Years with Lennox-Gastaut Syndrome

The biopharmaceutical company UCB announced that the US Food and Drug Administration (FDA) has approved fenfluramine for the treatment of seizures in patients with Lennox-Gastaut syndrome. Fenfluramine was previously approved for reducing seizures in patients with Dravet syndrome.

In March 2022, UCB acquired fenfluramine when it acquired the pharmaceutical company Zogenix. Fenfluramine is marketed as Fintepla. Fenfluramine is approved as an oral solution for patients aged ≥2 years who have Lennox-Gastaut syndrome or Dravet syndrome. UCB has been given pediatric exclusivity for fenfluramine by the FDA.

The company stated in a news release announcing the approval that fenfluramine may be given concomitantly with other antiseizure medications because as a serotonergic agent, fenfluramine has a different mechanism of action than other antiseizure medications on the market. In the company’s news release, Kelly Knupp, MD, of Children’s Hospital Colorado, said, “As a complementary therapy, fenfluramine offers a different mechanism of action and demonstrated ability to significantly reduce the number of seizures associated with a drop, a critical measure for managing this severe form of epilepsy.”

In granting the approval, the FDA analyzed the results of a phase 3 randomized clinical trial of oral fenfluramine in 263 patients aged 2 to 35 years who had received a diagnosis of Lennox-Gastaut syndrome. Patients taking fenfluramine had significantly fewer drop seizures compared with patients taking the placebo. Furthermore, 24% of patients taking fenfluramine had a ≥50% reduction in the frequency of drop seizures.

Adverse reactions associated with fenfluramine included decreased appetite, diarrhea, vomiting, fever, upper respiratory tract infections, and bronchitis. Other adverse reactions were fatigue, somnolence, sedation, and lethargy.

When fenfluramine was previously available for weight loss, some patients developed valvular heart disease or pulmonary hypertension. Consequently, cardiac monitoring is required before, during, and after patients receive fenfluramine for Lennox-Gastaut syndrome or Dravet syndrome. Patients should have an echocardiogram before starting fenfluramine, every 6 months during the first 2 years on fenfluramine, annually after 2 years, and again within 6 months of discontinuation.

Contraindications to fenfluramine use are valvular heart disease, pulmonary arterial hypertension, and monoamine oxidase inhibitor use within the previous 14 days. The efficacy and risks of adverse events with fenfluramine may be affected by many other medications, so clinicians need to be aware of the warnings and precautions.

The company listed several other warnings for fenfluramine use, such as an increase in blood pressure, mydriasis, or angle closure glaucoma. Although it may cause weight loss, the company stated that weight loss was temporary in most patients. As a serotonergic agent, fenfluramine may cause serotonin syndrome, and patients should be carefully monitored when they also take other medications that raise serotonin levels. Finally, like other antiseizure medications, patients should be monitored for suicidal thoughts or mood changes.

Fenfluramine is a Schedule IV substance and will only be available to prescribers through the Fintepla Risk Evaluation and Mitigation Strategy program. The company stated in the news release that the purpose of the program is to prevent off-label use for weight loss and ensure that the need for cardiac monitoring is understood.

“UCB is committed to supporting patient access to fenfluramine, and as part of that commitment, Zogenix Central, a comprehensive support program, will provide ongoing product assistance to patients, caregivers, and their medical teams,” stated the company in the news release.

Source

UCB. U.S. FDA approves Fintepla (fenfluramine) oral solution for treatment of seizures associated with Lennox-Gastaut syndrome (LGS). News release. Published March 28, 2022. Accessed October 10, 2022. https://www.ucb.com/stories-media/Press-Releases/article/US-FDA-Approves-FINTEPLAR-Vfenfluramine-Oral-Solution-for-Treatment-of-Seizures-Associated-with-Lennox-Gastaut-Syndrome-LGS.