Supernus Pharmaceuticals has announced that its drug candidate, SPN-820, exhibited a rapid and substantial effect in a Phase IIa trial involving adults with major depressive disorder (MDD). The study (NCT06235905) met its primary endpoint, demonstrating a clinically meaningful improvement of -6.1 on the Hamilton Depression Rating Scale-6 items (HAM-D6) at two hours, which further improved to -9.6 by day 10. Notably, suicidal ideation decreased by 80%, from 12.5% at baseline to 2.6% on day ten.
Commonly prescribed antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), often require several weeks to produce noticeable effects. SPN-820 is being developed as a rapid-acting treatment to provide quicker symptom relief, particularly for MDD patients at risk of suicidal ideation.
Study Details and Tolerability
The open-label study enrolled 40 adults, with 38 completing the 10-day treatment period. Supernus reported that SPN-820 was well-tolerated, with adverse events (AEs) including headache, nausea, and sleepiness.
Mechanism of Action
SPN-820 is a first-in-class, oral small molecule drug designed to enhance synaptic function in the brain by activating the mechanistic target of rapamycin complex 1 (mTORC1) pathway. This mechanism boosts synaptic activity and cellular metabolism, potentially leading to improved brain function. The company anticipates that SPN-820 will offer rapid antidepressant benefits without the dissociative side effects associated with other antidepressants.
Comparison with Existing Therapies
SSRIs like sertraline (Zoloft) and paroxetine (Paxil) are associated with side effects such as dizziness, weight gain, and sexual dysfunction, which can affect patient adherence and potentially worsen depression symptoms. SPN-820 aims to provide a more tolerable and rapid-acting alternative.
Ongoing Phase IIb Study
An ongoing Phase IIb study (NCT05066672) is evaluating SPN-820 in approximately 227 adult patients with treatment-resistant depression. Supernus expects to complete enrollment by November of this year, with topline results anticipated in the first half of 2025, according to CEO Jack Khattar.
Executive Commentary
Supernus’ CEO Jack Khattar stated, “These Phase IIa data underscore our belief that SPN-820 has the potential as a novel treatment option for patients with depression, with the opportunity to decrease symptoms quickly and without certain burdensome side effects.”
