Supernus Pharmaceuticals (SUPN) Study Update summary

Study overview and objectives

• Phase 2a open-label study evaluated SPN-820, a first-in-class oral mTORC1 modulator, in 40 adults with major depressive disorder (MDD) as adjunctive therapy, focusing on rapid onset, efficacy, safety, and dosing every three days.

• Subjects maintained stable antidepressant therapy and received 2400 mg SPN-820 on Days 1, 4, and 7 across 8 sites.

• Primary endpoint: change from baseline in HAM-D6 score; secondary: MADRS score; safety endpoints included adverse events, suicidal ideation, dissociation, and psychosis assessments.

• 95% completion rate; 2.5% discontinued due to adverse event (hypertension, not drug related) or non-compliance.

• Study design included serial efficacy and safety assessments over 10 days, with three doses of SPN-820.

Key efficacy results

• Rapid reduction in depression symptoms observed within two hours of first dose; HAM-D6 score dropped by 6.1 points at two hours and by 9.6 at Day 10.

• MADRS score decreased by 16.6 points at four hours post-dose, with a total reduction of 22.9 points by Day 10.

• Most participants reached remission (MADRS ≤10) by Day 10, indicating a high rate of clinical response.

• 80% reduction in suicidal ideation by Day 10; only 2.6% had ideation at study end versus 12.5% at baseline, with no suicidal behavior reported.

• Single dose effect lasted up to 72 hours.

Safety and tolerability

• 62.5% experienced treatment-emergent adverse events (TEAEs), mostly mild or moderate; no severe or serious AEs reported.

• Most common AEs: headache and nausea (20% each), somnolence (15%), dizziness (10%).

• Additional AEs included cognitive disorder, dry mouth, fatigue, nasal decongestion, and paresthesia oral.

• Only one discontinuation (2.5%) due to hypertension, not drug-related; no dissociative or psychotic symptoms observed.

• Safety profile considered benign and well-tolerated, with ongoing monitoring in future studies.