Dravet syndrome treatment bexicaserin shows promise in trial
Data show sustained reductions in seizure frequency
Treatment with the experimental oral therapy bexicaserin led to sustained reductions in seizure frequency for children with Dravet syndrome and other types of developmental and epileptic encephalopathies (DEEs), according to new data from the PACIFIC Phase 1/2a clinical trial and its open-label extension study.
The findings were announced by Longboard Pharmaceuticals, the company developing bexicaserin and sponsoring the studies.
“We are thrilled to see a sustained, durable response in seizure reduction and a favorable safety and tolerability profile across a broad range of DEE patients,” Randall Kaye, MD, chief medical officer at Longboard, said in a company press release. The new data “provide further support to bexicaserin’s potential to offer a highly differentiated and best-in-class profile,” Kaye said.
Seizures are one of the most problematic symptoms of Dravet syndrome and other DEEs, and they can be hard to control with available medications. Bexicaserin, formerly known as LP352, is designed to reduce seizure frequency by reducing the abnormal activity of brain cells. (Seizures are marked by uncontrolled bursts of brain cell activity.) The therapy specifically targets a protein receptor called the 5-HT2c receptor.
The Phase 1/2a PACIFIC study (NCT05364021) was conducted to investigate the safety and efficacy of bexicaserin in children with Dravet and other DEEs. Participants underwent an initial monitoring period lasting about a month, then were randomly assigned to take bexicaserin or a placebo, on top of existing anti-seizure medications. Doses of the study drug were adjusted for about two weeks, then maintained for about two months.
Dravet syndrome treatment shows results
Top-line results from PACIFIC were announced in January. The study enrolled a total of 52 patients, and findings showed the median reduction in seizure frequency was significantly higher with bexicaserin than placebo (53.3% vs. 20.8%).
Among the four study participants with Dravet syndrome, all of whom were given bexicaserin, median seizure frequency was reduced by 72.1%.
Safety data from PACIFIC showed bexicaserin was generally tolerated well by most patients. The most common side effects were sleepiness or lethargy, decreased appetite, constipation, and diarrhea. There were three serious safety issues reported: one instance of serious constipation, one patient who experienced an increase in seizure frequency, and one broken ankle. Seven patients quit the trial due to side effects in the initial dose-adjustment period, and another two stopped taking bexicaserin due to side effects during maintenance dosing.
All of the participants who completed the placebo-controlled PACIFIC study entered into an ongoing open-label Phase 2 extension study (NCT05626634), in which all are being treated with bexicaserin for as long as about a year.
New interim data showed that, after six months in the extension study, the median seizure frequency had decreased by 56.1% compared with rates from before PACIFIC. Notably, the median decrease in seizure frequency was similar for patients who had been on therapy in the original trial (54.9%) and for those who had originally been on placebo but switched to bexicaserin in the extension study (57.3%).
“We saw compelling seizure reduction in the PACIFIC placebo patients who transitioned to bexicaserin in the OLE [open-label extension],” Kaye said.
Of the 41 patients who entered the extension study, 39 are still participating. One chose to stop taking bexicaserin due to medication side effects, specifically lethargy, and another no longer wished to participate.
The most common safety issues that have been reported in the study (including side effects of bexicaserin as well as other notable safety findings) are upper respiratory tract infections, COVID-19, pneumonia, sinusitis (sinus inflammation), seizures, and decreased appetite.
Buoyed by these positive findings, Longboard is working to start an expanded access program that would allow patients who complete the OLE to continue taking bexicaserin long-term.
“Given the tremendous unmet need in patients living with DEEs, we are committed to rapidly advancing the development of bexicaserin,” Kaye said. “We expect to provide additional analyses of these participants as they progress in the OLE Study and transition to our Expanded Access Program. With an End of Phase 2 meeting scheduled this summer, we remain on track to initiate our global Phase 3 program for bexicaserin later this year.”
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