A phase 2 study of forvisirvat (SP-624), a SIRT6 activator, for safety and efficacy in adults with major depressive disorder

Forvisirvat (SP-624), an oral SIRT6 activator with antidepressant activity shown in animal models, was tested in a phase 2 randomized trial for adults with major depressive disorder (MDD). In the SP-624-201 study, participants received forvisirvat 20 mg daily or placebo for 4 weeks. The trial assessed safety and change in depressive symptoms using the Montgomery-Asberg Depression Rating Scale, with the main endpoint comparing baseline to week 4. The study found no significant difference between groups on the primary outcome. However, post-hoc analyses reported sex-specific results: women treated with forvisirvat showed greater overall improvement than men. Safety findings indicated a generally favorable profile, with headache as the most common treatment-emergent event, and no serious adverse events in the forvisirvat group; a phase 2b/3 trial is planned.