SPN-820 Fails Phase 2b Trial for Treatment-Resistant Depression

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Supernus Pharmaceuticals announced topline results from their phase 2b trial on February 20, 2025, finding participants with treatment-resistant depression on SPN-820 did not demonstrate statistically significant improvements on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score.¹

These results follow previously positive results from the company’s open-label phase 2a trial which had shown SPN-820’s rapid antidepressant effects, reducing depressive symptoms and suicidal ideation significantly within 2 hours of administration among patients with major depressive disorder (MDD).² The phase 2a trial has also showed SPN-820 reduced suicidal ideation by 80%.

“We are disappointed that the trial did not meet its primary endpoint in this patient population,” said Jack Khattar, president and CEO of Supernus, in a statement.¹ “We will continue to analyze these data and discuss the future of the program with our development partner, Navitor Pharmaceuticals.”

These findings came from a multicenter, randomized, double-blind, placebo-controlled trial examining the efficacy and safety of SPN-820 over 4 weeks and then a week of blinded placebo washout in patients with treatment-resistant depression. The study included about 250 patients from approximately 40 clinical sites.

SPN-820, a novel, first-in-class intracellular moderator of the mechanistic target of rapamycin complex 1 (mTORC1), held promise in orally treating depression.² The medication worked by enhancing synaptic activity and cellular metabolism in the brain.

The primary outcome of the phase 2b trial was the change from baseline to the end of the treatment on the MADRS total score.¹ Participants did not demonstrate statistically significant improvement on the MADRS total score from baseline to week 4 compared with placebo (-12.3 vs -11.9; standard error for both: 0.96). The study observed no treatment difference between SPN-820 and placebo for the secondary endpoints.

The one thing consistent with the phase 2a trial was the safety profile of SPN-820. The drug had a comparable safety profile to previous clinical trials, with few adverse events and no serious or severe adverse events. The phase 2a trial showed common adverse events of SPN-820 including headache, nausea, somnolence, and dizziness.²

“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,” Khattar said.¹

References

1. Supernus Announces Topline Results from Phase 2b Study in Adults with Treatment Resistant Depression. Supernus Pharmaceuticals. February 18, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-announces-topline-results-phase-2b-study-adults. Accessed February 20, 2025.

2. Derman, C. SPN-820 Decreases Depressive Symptoms Within Hours of First Dose in Phase 2a Trial, HCPLive. November 1, 2024. https://www.hcplive.com/view/spn-820-decreases-depressive-symptoms-within-hours-of-first-dose-in-phase-2a-trial. Accessed February 20, 2025.