SPN-820 Fails to Meet Primary Endpoint in Study of Adults with Treatment-Resistant Depression

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Supernus Pharmaceuticals announced that SPN-820 for the treatment of adults with treatment-resistant depression (TRD) failed to demonstrate a statistically significant improvement on the primary endpoint of change from baseline in a phase 2b study.¹

“We are disappointed that the trial did not meet its primary endpoint in this patient population,” said Jack Khattar, President and CEO of Supernus. “We will continue to analyze these data and discuss the future of the program with our development partner, Navitor Pharmaceuticals. I’d like to thank the patients, coordinators and investigators, as well as the development team at Supernus, for their time and efforts in conducting this trial.”

The phase 2b study was a multi-center, randomized, double-blind, placebo-controlled trial of SPN-820 in adults with TRD. The study examined the efficacy and safety of SPN-820 over a course of 4 weeks of treatment and then a week of blinded placebo-washout in approximately 250 patients from approximately 40 clinical sites. The primary outcome measure was the change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score to week 4; SPN-820 did not achieve statistically significant improvement (SPN-820 [LS mean ± Standard Error]: -12.3 ± 0.96 vs placebo: -11.9 ± 0.96; P = not significant). There was no treatment difference between SPN-820 and placebo in the change from baseline to week 4 for the secondary endpoints. The safety profile of SPN-820 was consistent with previous clinical trials, showing few adverse events.

This news comes at the heels of a positive update for SPN-820 in adults with major depressive disorder (MDD).² In a 10-day, phase 2, open-label clinical trial, SPN-820 as an adjunct treatment provided rapid and substantial improvement in adults with MDD who had not achieved full symptom relief from conventional antidepressants. The trial included 40 participants aged 18 to 65 with moderate to severe MDD symptoms. Participants received 2400 mg of oral SPN-820 every 3 days. The study’s primary efficacy measures were HAM-D6 and MADRS score changes. Safety outcomes included adverse events, vital sign monitoring, and assessments for dissociative symptoms, hallucinations, and suicidality. The trial showed a 50% reduction in MADRS scores, with 63.2% of participants achieving remission by day 10. This suggests that SPN-820 could be an effective alternative for patients who do not fully respond to traditional antidepressants. The new information was presented via poster session at the 30th Annual Nevada Psychiatric Association National Psychopharmacology Update.

Promising data on SPN-820 was also shared at the 63rd Annual Meeting of the American College of Neuropsychopharmacology in Phoenix, Arizona.³ 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. Specifically, the study looked at every 3-day dosing; the agent was administered on day 1, 4, and 7. Investigators examined changes in MADRS, HAM-D 6, and CGIS scores. They found a very rapid improvement in HAM-D 6 scores in 2 hours, and after each subsequent dose, slightly better improvement. Additionally, MADRS scores improved, and suicide ideation reduced. SPN-820 demonstrated no serious or severe adverse events and approximately 40% of the patients had no 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.

References

1. Supernus announces topline results from phase 2b study in adults with treatment resistant depression. News release. February 18, 2025. Accessed February 20, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-announces-topline-results-phase-2b-study-adults

2. McSweeney M. SPN-820 shows rapid and significant improvement in major depressive disorder symptoms. Psychiatric Times. February 12, 2025. https://www.psychiatrictimes.com/view/spn-820-shows-rapid-and-significant-improvement-in-major-depressive-disorder-symptoms

3. Duerr HA, Upadhyaya H. SPN-820: rapid-acting antidepressant shows promising phase 2 results. Psychiatric Times. December 11, 2024. https://www.psychiatrictimes.com/view/spn-820-rapid-acting-antidepressant-shows-promising-phase-2-results