SPN-820: Rapid-Acting Antidepressant Shows Promising Phase 2 Results

CONFERENCE REPORTER

Promising data on SPN-820 for major depressive disorder (MDD) was presented at the 63rd Annual Meeting of the American College of Neuropsychopharmacology in Phoenix, Arizona.¹ Himanshu Upadhyaya, MBBS, MBA, presented findings from a phase 2 open-label trial exploring SPN-820, a novel first-in-class, rapid-acting antidepressant. The study examined the agent’s safety and tolerability when used as adjunctive therapy for adults with MDD.

“Traditional antidepressants such as selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, bupropion and such do take time to work, and they're not effective in all patients. So there's definitely a need for rapid reacting antidepressant with potential for improvement in suicidality,” Upadhyaya told Psychiatric Times in an interview.

The phase 2 study focused on evaluating the safety, tolerability, and preliminary efficacy of SPN-820 in a cohort of adults (N=40) with MDD who had not achieved sufficient symptom control with their current FDA-approved treatments, he said. Specifically, the study looked at every 3 day dosing; the agent was administered on day 1, 4, and 7.

“We found that the drug was very well tolerated,” he said. “It had no serious or severe adverse event.” Almost 40% of the patients had no adverse events, he said, but he acknowledged that it meant approximately 60% of the patients did experience adverse events. The most common adverse events were headache (20.0%), nausea (20.0%), somnolence (15.0%), and dizziness (10.0%).1 However, there was no study discontinuation due to adverse events.

In considering efficacy, Upadhyaya and colleagues looked at MADRS, HAM-D 6, and CGIS scores. “What we found is a very rapid improvement in HAM-D 6 scores in 2 hours…and after each subsequent dose we saw slightly better improvement,” he told Psychiatric Times. Improvement was also seen with MADRS scores. They also saw reduced suicide ideation.

SPN-820 is a small molecule that can be taken orally, Upadhyaya said, with participants in this study taking capsules. It is a novel, first in class novel mechanism of action, he added. “The agent works intracellularly to increase mTORC1 activity, which then, in the presence of BDNF, leads to increased protein synthesis related to synaptogenesis,” he explained. ”So it increases the number of synapses, dendritic spines, and the connection that strengthens the synaptic connections that is thought to be involved in the rapid antidepressant effect.”

Unlike other rapidly acting antidepressants, SPN-820 may ultimately have similar mechanisms of action, he added, but the other agents worked indirectly by the activity on NMDA receptor or 5HT receptors. “We bypass that and go straight intracellularly and improve mTORC1 activity,” Upadhyaya explained. “Because of that, we don’t expect any abuse potential with this product.” Similarly, other rapidly acting antidepressants, both on the market and under investigation, may result in dissociative symptoms, but this trial did not find any evidence of such.

For more information from Dr Upadhyaya on SPN-820 as well as highlights from other sessions and posters, subscribe to the Psychiatric Times e-newsletter.

Reference

1. Upadhyaya H. SPN-820, a Novel first-In-Class, Rapid-Acting antidepressant: Topline Results of a Phase 2, open-Label, Adjunctive Therapy Trial in Adults with Major Depressive Disorder. Presented at: 63^rd Annual Meeting of the American College of Neuropsychopharmacology. Phoenix, Arizona; December 8-12