Supernus Reports Positive Interim Data from Phase 2a Study of SPN-817 in Epilepsy

Supernus Pharmaceuticals, Inc. has recently shared interim results from its ongoing Phase 2a clinical trial of SPN-817, a new acetylcholinesterase inhibitor, targeting treatment-resistant seizures in adults. This drug, representing a novel approach to epilepsy treatment, is being examined for its safety, tolerability, and efficacy in reducing seizure frequency when used in conjunction with other anti-seizure medications (ASMs).

As of May 1, 2024, the interim data includes 41 enrolled participants, with 19 completing the maintenance phase. Within this cohort, 16 individuals experienced focal seizures. Key findings highlight a significant reduction in seizure frequency for those taking 3mg to 4mg doses of SPN-817 twice daily. Specifically, there was a 75% median reduction in focal seizures during the maintenance phase and an 86% reduction during the open-label extension phase.

Further analysis during the maintenance phase showed that 81% of participants with focal seizures experienced a reduction of 30% or more in their seizure frequency, while 63% saw a reduction of 50% or more, and 19% achieved a reduction of 75% or more. For participants with more severe conditions, characterized by an average baseline of over 11.3 seizures per 28 days, median seizure reductions were 74% in the maintenance period and 86% in the open-label extension.

In subjects taking three or more other ASMs, the median seizure reduction was 70% during the maintenance phase and 60% during the open-label extension. Responder analysis in this subgroup indicated that 100% of participants experienced at least a 30% reduction in seizures, 82% saw a 50% reduction, and 27% achieved a 75% reduction.

When considering all doses (1mg to 4mg, twice daily), the overall median seizure reduction was 58% during the maintenance phase and 38% in the open-label extension phase. Cognitive function assessments using Epitrack®, a validated tool for epilepsy patients, showed that among twelve subjects, 83% displayed either improvement or no change in cognitive abilities.

SPN-817 demonstrated a safety profile consistent with other acetylcholinesterase inhibitors. The discontinuation rate due to adverse events (AEs) was 22% during the titration period and 2.4% during the maintenance phase. Common AEs included nausea, diarrhea, headache, dizziness, and decreased appetite. Other observed AEs were fatigue, insomnia, vomiting, blurred vision, somnolence, and irritability.

Jack Khattar, President and CEO of Supernus, commented on the promising results, noting the potential of SPN-817 to address the needs of patients with treatment-resistant epilepsy. The company plans to use this data to inform the design of a Phase 2b clinical study, which is slated to begin by the end of 2024. This ongoing Phase 2a study will extend further to explore ways to improve tolerability during the titration phase. Full topline results are expected in the second half of 2024.

SPN-817, a synthetic form of huperzine A, has shown effectiveness in preclinical models for treating partial seizures and Dravet Syndrome. The drug has been granted Orphan Drug designation by the FDA for both Dravet Syndrome and Lennox-Gastaut Syndrome. The development of a novel extended-release oral dosage form is critical due to serious side effects observed with immediate-release formulations.

Supernus Pharmaceuticals is dedicated to advancing treatments for CNS diseases, with a portfolio that includes approved medications for conditions such as epilepsy, migraine, ADHD, and Parkinson's disease. The company continues to invest in the development of innovative CNS therapies, aiming to address unmet medical needs in these areas.