Bexicaserin hydrochloride

Table of contents

• What is bexicaserin hydrochloride?
• How does bexicaserin hydrochloride work?
• Which conditions is it used or studied for?
• How is bexicaserin hydrochloride given?
• What do the clinical trials show?
• What side effects are known?

What is bexicaserin hydrochloride?

Bexicaserin hydrochloride (also known as bexicaserin, LP352, or AN 352) is a chemically synthesised small molecule being developed as an antiepileptic medicine.^[4] It is classified as a serotonin receptor agonist and belongs to a group of drugs that act on the 5-HT2C receptor.^[5] The medicine is being developed by Longboard Pharmaceuticals, Inc.^[4]

Bexicaserin hydrochloride is an investigational substance with no marketing authorisation in the product records of the trials listed here. It has received orphan drug designation from the US Food and Drug Administration (FDA) for the treatment of Dravet syndrome, a status given to encourage development of medicines for rare diseases.^[4]

How does bexicaserin hydrochloride work?

Bexicaserin hydrochloride acts as an agonist at the 5-HT2C serotonin receptor, meaning it activates this receptor in the brain.^[5] The 5-HT2C receptor is part of the serotonin system, which is involved in regulating various brain functions. By stimulating this receptor, the medicine is thought to influence signalling pathways that may help control seizures.^[5]

The target of bexicaserin hydrochloride is the HTR2C gene product, a receptor protein found in the central nervous system.^[5] In the KEGG drug database, the medicine is described as an antiepileptic with a comment that it is intended for the treatment of seizures associated with developmental and epileptic encephalopathies.^[5]

Which conditions is it used or studied for?

• Dravet syndrome — a rare and severe form of epilepsy that begins in infancy and is associated with frequent, difficult-to-control seizures. Bexicaserin hydrochloride has orphan drug designation from the FDA for this condition.^[4]
• Developmental and epileptic encephalopathies (DEEs) — a group of rare epilepsies in which seizures and developmental delay occur together. Two of the three Phase 3 trials are focused on this broader group.^[3][1]

How is bexicaserin hydrochloride given?

Bexicaserin hydrochloride is formulated as an oral solution. It can be given by mouth, or through a nasogastric tube or a percutaneous endoscopic gastrostomy (PEG) tube.^[2] The trials describe a 36 mg dose in this oral solution form. In the trials, the medicine is compared with a placebo oral solution that does not contain the active substance.

What do the clinical trials show?

Three Phase 3 trials of bexicaserin hydrochloride are currently authorised and listed in trial registries. All three are interventional studies. The trials are placebo-controlled or open-label and focus on Dravet syndrome and developmental and epileptic encephalopathies.

What conditions are being studied?

• One trial (NCT06660394) is dedicated to Dravet syndrome, with a planned enrolment of 184 participants.^[2]
• Two trials are focused on developmental and epileptic encephalopathies: one placebo-controlled trial (NCT06719141) with 283 planned participants, and one open-label safety study (2024-514974-39-00) with 335 planned participants.^[3][1]

What phases and status do the trials have?

All three trials are Phase 3 studies, the stage of research that typically involves larger groups of participants and aims to confirm effectiveness and monitor safety. The status of all three trials is "Authorised", meaning they have received regulatory approval to begin or continue but are not yet completed.

What are the trials measuring?

The two placebo-controlled trials measure the frequency percent change in countable motor seizures during a maintenance period compared with baseline.^[2][3] Countable motor seizures are seizures that involve visible movement and can be counted by caregivers or clinicians. The open-label trial focuses on safety and tolerability, measuring treatment-emergent adverse events, including serious adverse events and those leading to discontinuation, changes in laboratory parameters, physical examination findings, vital signs, ECGs, growth parameters, and changes in suicidality or depression as rated by standard questionnaires.^[1]

Who can take part in these trials?

The trials enrol children and adults. The Dravet syndrome trial includes children and adults with Dravet syndrome.^[2] The two DEE trials include children and adults with developmental and epileptic encephalopathies.^[3][1] Specific eligibility criteria are available in the individual trial records.

What side effects are known?

The supplementary sources provided do not include a detailed side-effect profile for bexicaserin hydrochloride. The open-label Phase 3 trial is specifically designed to evaluate safety and tolerability, including the incidence and severity of treatment-emergent adverse events, serious adverse events, and adverse events leading to discontinuation.^[1] Detailed information on side effects will become available as these trials report their results.