The Food and Drug Administration (FDA)’s Psychopharmacologic Drug Advisory Committee and Drug Safety and Risk Management Advisory Committee voted in favor (14 yes, 2 no, 1 abstain) of the approval of esketamine nasal spray (Spravato; Janssen) for the treatment of adult patients with treatment-resistant depression (TRD).
The decision was based on data from five Phase 3 studies assessing the safety and efficacy of esketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist; patients in these studies had a history of inadequate response to least 2 prior antidepressants and generally had more severe symptoms than those who participated in antidepressant studies for previously approved drugs.
Results from 2 of these Phase 3 studies (1 short-term, 1 long-term), which primarily provided the evidence to support effectiveness, showed that treatment with esketamine nasal spray plus a newly initiated oral antidepressant was associated with a statistically significant, clinically meaningful, rapid, and sustained improvement of depressive symptoms vs placebo nasal spray plus a newly initiated oral antidepressant.
With regard to safety, the adverse events identified as those of greatest concern were sedation, dissociation, and blood pressure increases, most of which occurred within the first 2 hours of administration. To address these issues, the committees proposed a Risk Evaluation and Mitigation Strategy (REMS) which would call for esketamine administration to occur only in healthcare settings where patients can be monitored for at least 2 hours. In addition, pharmacies, prescribers, and healthcare settings would need to be certified in order to dispense the drug; esketamine would not be directly dispensed to a patient. Moreover, to monitor the risks associated with treatment, patients would need to be enrolled in a registry.
The proposed presentation of esketamine would be a 28mg unit-dose nasal spray device; the product would be classified as a Schedule III controlled substance. Currently, the only FDA-approved treatment for TRD is a fixed-dose combination of fluoxetine, a selective serotonin reuptake inhibitor, and olanzapine, an atypical antipsychotic.
Although not bound by the committees’ recommendations, the FDA does take them into consideration when making decisions on approval. The Prescription Drug User Fee Act (PDUFA) date for Spravato has been set for March 4, 2019.
For more information visit FDA.gov.