Seizure treatment bexicaserin gets FDA breakthrough therapy nod
Therapy aimed at seizures associated with Dravet syndrome, other DEEs
The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to Longboard Pharmaceuticals‘ bexicaserin to treat seizures associated with developmental and epileptic encephalopathies (DEEs), including Dravet syndrome, in patients 2 and older.
The designation is meant to accelerate the development and regulatory review of medications intended to treat serious or life-threatening conditions.
The decision was based on data from the PACIFIC Phase 1/2a trial (NCT05364021) and its open-label extension study showing bexicaserin led to sustained reductions in seizure frequency in children with Dravet and other DEEs.
“The FDA will work closely with us to provide guidance on subsequent development of bexicaserin to help us design and conduct a development program as efficiently as possible,” Randall Kaye, MD, Longboard’s chief medical officer, said in a company press release. “We are looking forward to initiating our global Phase 3 program later this year.”
Dravet syndrome is a type of epilepsy characterized by frequent and prolonged seizures, uncontrolled bursts of electrical activity in the brain, usually starting early in infancy. In most cases, the disease is caused by mutations in the SCN1 gene.
Seizures hard to control
Seizures in Dravet and other DEEs are often hard to control with available medications and may lead to developmental delays.
Bexicaserin, previously known as LP352, is an oral therapy designed to specifically activate 5-HT2C receptors in the brain and spinal cord. By activating these receptors, the treatment is expected to reduce the abnormal nervous system activity that characterizes seizures.
“Most of those living with DEEs do not have access to novel medications, nor have they had the opportunity to participate in trials designed to collect data specific to their condition,” said Gabrielle Conecker, co-founder and executive director of Decoding Developmental Epilepsies. “I am thrilled that we are making strides towards advancing DEE research for the broader population and pleased that there is a move towards increased equity and access for underserved patients and families to clinical trials and potential novel treatments.”
The PACIFIC study assessed the safety and efficacy of bexicaserin in 52 adolescents and adults, ages 12 to 65, with different types of DEE, including Dravet, at sites in the U.S. and Australia. After an initial monitoring period, participants were randomly assigned to receive bexicaserin or a placebo, together with approved anti-seizure medications, for about two months.
The treatment was shown to be generally well tolerated, with sleepiness or lethargy, decreased appetite, constipation, and diarrhea, being the most commonly reported side effects. Three patients saw serious adverse events, and seven dropped out of the study.
The reduction in seizure frequency was significantly higher in patients receiving bexicaserin than in those on placebo (53.3% vs. 20.8%). Among the four patients with Dravet, all of whom were given bexicaserin, median seizure frequency was reduced by 72.1%.
All of those who completed the PACIFIC study entered into an ongoing, open-label Phase 2 extension study (NCT05626634) in which they are being treated with bexicaserin for about a year. After six months, median seizure frequency had decreased by 56.1% compared with rates from before PACIFIC.
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