SILVER SPRING, Md.—Zogenix, Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved Fintepla (fenfluramine) for the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older. Dravet syndrome, a rare, life-threatening, chronic form of epilepsy, is often characterized by severe and unrelenting seizures despite medical treatment.
“Dravet syndrome … takes a tremendous toll on both patients and their families,” said Billy Dunn, M.D., director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, in an FDA press release. “Fintepla offers an additional effective treatment option for the treatment of seizures associated with Dravet syndrome. The FDA will continue to work with companies on drug development for Dravet syndrome and other types of epilepsy.”
“The approval of Fintepla by the FDA is a significant milestone we are proud to celebrate with the patients and families living with Dravet syndrome. We began this global development program nearly six years ago after researchers in Belgium recognized the potential of fenfluramine, a drug with distinct pharmacology from all other anticonvulsant agents, to treat intractable seizures in Dravet syndrome,” added Stephen J. Farr, Ph.D., president and chief executive officer of Zogenix. “Our heartfelt gratitude goes to the patients, families, and everyone who supported the rigorous development program that led to Fintepla’s approval.”
The FDA’s approval was based on data from Phase 3 clinical trials, which were published in The Lancet and JAMA Neurology, and safety data from an open-label extension trial in which many patients received Fintepla for up to three years. The studies measured the change from baseline in the frequency of convulsive seizures.
When added to existing treatment regimens, Fintepla significantly reduced the monthly convulsive seizure frequency compared to placebo in study patients whose seizures weren’t adequately controlled on one or more anti-epileptic drugs. These reductions were seen within 3-4 weeks, and remained generally consistent over the 14- to 15-week treatment periods. Most study patients responded to treatment with Fintepla within three to four weeks, and effects remained consistent over the treatment period.
The most common adverse reactions in clinical studies were decreased appetite; drowsiness, sedation and lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, malaise, asthenia; ataxia, balance disorder, gait disturbance; increased blood pressure; drooling, salivary hypersecretion; pyrexia; upper respiratory tract infection; vomiting; decreased weight; risk of falls; and status epilepticus.
“There remains a huge unmet need for the many Dravet syndrome patients who continue to experience frequent severe seizures even while taking one or more of the currently available anti-seizure medications. Given the profound reductions in convulsive seizure frequency seen in the Fintepla clinical trials, combined with the ongoing, robust safety monitoring that will be part of its use, I feel Fintepla will offer an extremely important treatment option for Dravet syndrome patients,” stated Joseph Sullivan, M.D., director of the Pediatric Epilepsy Center of Excellence at the UCSF Benioff Children’s Hospitals and the principal investigator for Fintepla in Dravet syndrome.
Fintepla labeling includes a boxed warning stating that the drug is associated with valvular heart disease (VHD) and pulmonary arterial hypertension (PAH). Because of these risks, patients must have echocardiograms performed before treatment, every six months during treatment, and once three to six months after treatment is discontinued. If the echocardiogram shows signs of VHD, PAH or other cardiac abnormalities, health care professionals must consider the benefits and risks of continuing treatment with Fintepla for the patient.
Because of the VHD and PAH risks, Fintepla will be launched with restricted distribution through the Fintepla Risk Evaluation and Mitigation Strategy (REMS) program. Fintepla is expected to be available through Zogenix’s specialty pharmacy partner by the end of July. Zogenix is also launching Zogenix Central, a support service meant to provide ongoing product assistance to patients, caregivers and their medical teams.
“Having a new FDA-approved treatment option is so important because it improves our ability to optimize each patient’s treatment. Moreover, because families living with Dravet syndrome never know when the next seizure is going to occur, whether they will end up in the E.R., or what the consequences might be following the seizure, having a strong support program like Zogenix Central to reduce the strain on families is very welcome,” noted Mary Anne Meskis, executive director of the Dravet Syndrome Foundation. “This will allow family members to remain focused on providing the best care of their loved one with Dravet.”