Long-Term Seizure Reduction Seen with 5-HT2C Receptor Superagonist Treatment in Those with DEEs
Treatment of seizures using bexicaserin (Lundbeck, Deerfield, IL) was associated with improved long-term efficacy, safety, and tolerability outcomes for individuals with developmental and epileptic encephalopathies (DEEs) in the results of a 12-month open-label extension (OLE) study. Individuals treated with bexicaserin during the 12-month OLE period demonstrated an overall median reduction of 59.3% in the frequency of countable motor seizures. Bexicaserin, an oral 5-hydroxytryptamine 2C (5-HT2C) receptor superagonist, received Food and Drug Administration (FDA) Breakthrough Therapy designation in the summer of 2024.
The OLE study enrolled all 41 individuals who completed the double-blind, placebo-controlled phase 1b/2a PACIFIC clinical trial (NCT05364021), which investigated the safety, tolerability, efficacy, and pharmacokinetics of bexicaserin for people aged 12 to 65 years with Dravet syndrome (DS; n=3), Lennox-Gastaut syndrome (LGS; n=20), and other DEEs (n=18). In PACIFIC, participants were randomized to receive either bexicaserin (n=31) or placebo (n=9) 3 times daily, while in the OLE, all participants received bexicaserin.
Key results from the OLE study include the following:
- The overall median seizure reduction in countable motor seizures was 59.3% over the 12-month OLE period (n=40).
- Participants who received bexicaserin in the PACIFIC study (n=31) showed a median reduction of 60.4% in countable motor seizure frequency.
- Participants who received placebo in the PACIFIC study (n=9) showed a median reduction of 58.2% in countable motor seizure frequency after transitioning to bexicaserin in the OLE.
- 92.7% (n=38) of participants completed the full 12-month treatment period.
- The most common adverse events included upper respiratory tract infections, seizures, decreased appetite, lethargy, and fever.
“We are very pleased to observe a longer-term sustainable response, along with a favorable safety and tolerability profile over a 12-month period,” said Johan Luthman, EVP and Head of Research & Development at Lundbeck. “These results further reinforce our confidence in bexicaserin’s unique and potentially best-in-class profile. Considering the significant unmet needs of patients with DEEs, we are encouraged by the long-term sustainability of bexicaserin treatment.”