SPN-817 (Previously BIS-001)

SPN-817 (formerly, BIS-001) is an experimental treatment for Dravet syndrome. The medication contains a synthetic version of huperzine A, an acetylcholinesterase inhibitor that naturally occurs in the plant Huperzia serrata, commonly known as  Chinese, or toothed, club moss. Huperzine A has been used in traditional Chinese medicine to treat pain, inflammation, and cognitive disorders.

Biscayne Neurotherapeutics initially developed this potential treatment as BIS-001. Supernus Pharmaceuticals has since acquired the company, and is investigating it as an antiepileptic agent to treat complex partial seizures or focal impaired-awareness seizures (FIAS).

The U.S. Food and Drug Administration (FDA) designated BIS-001 an orphan drug for the treatment of Dravet syndrome in 2017. 

How does SPN-817 work?

Huperzine A is a molecule that inhibits, or blocks, the acetylcholinesterase enzyme. This enzyme works to break down acetylcholine, a signaling molecule in the brain.

Blocking this enzyme’s activity should lead to a rise in acetylcholine levels, which could trigger the release of gamma-aminobutyric acid (GABA) in specific brain cells (though researchers do not fully understand the mechanism). GABA is another signaling molecule in the brain that has an inhibitory effect on nerve cells. Because seizures are the result of overactive neuronal activity — resulting in the constant firing of electric signals among brain cells — the stimulating effect of huperzine A on GABA release may work to suppress seizures.

Compared to other acetylcholinesterase inhibitors, huperzine A has the advantage of easily crossing the blood-brain barrier and reaching cells of the brain.

SPN-817 in clinical trials

A Phase 1b clinical trial (NCT03156439), sponsored by Biscayne Neurotherapeutics, assessed the safety and tolerability of SPN-817 in eight healthy volunteers. Participants were given the experimental treated twice a day, with researchers increasing the dose every two to three days until a maximum daily dose of 2.5 mg was reached. Participants tolerated the treatment well, with mild to moderate, transient, and non-dose limiting adverse events.

A Phase 1/2 clinical trial (NCT03474770), also sponsored by Biscayne, was to open in April 2018 and enroll patients with focal impaired-awareness seizures at the Alfred Hospital and the Royal Melbourne Hospital in Australia. The trial’s status is not known. According to its website, participants were to be treated with SPN-817 twice a day at a starting dose of 0.25 mg. This dose would escalate until a maximum tolerated dose, or the target dose of 1.75 mg, were met, and patients would be treated twice daily for one month. This trial’s NCT document has not been updated since March 2018.


Last updated: July 27, 2020


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