The Janssen Pharmaceutical Companies of Johnson & Johnson announced that the US Food and Drug Administration (FDA) has approved the supplemental new drug application (sNDA) for SPRAVATO (esketamine) CIII nasal spray, taken with an oral antidepressant, to treat depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behaviour. SPRAVATO is the first and only approved medicine that has been shown to reduce depressive symptoms within 24 hours, providing a new option for significant symptom relief until a longer-term, comprehensive treatment plan can take effect.
The effectiveness of SPRAVATO in preventing suicide or in reducing suicidal ideation or behaviour has not been demonstrated. Use of SPRAVATO does not preclude the need for hospitalisation if clinically warranted, even if patients experience improvement after an initial dose of SPRAVATO. SPRAVATO carries a boxed warning regarding a Risk Evaluation and Mitigation Strategy (REMS) and the risk of suicidal thoughts and behaviours. SPRAVATO will be made available at REMS certified treatment centres. Janssen is working to educate and certify treatment centres in accordance with the REMS so healthcare providers can offer SPRAVATO to appropriate patients.
The sNDA approval is based on two identical Phase 3 clinical trials in which SPRAVATO plus comprehensive standard of care demonstrated a significant, rapid reduction of depressive symptoms within 24 hours, with some patients starting to respond as early as four hours. SPRAVATO plus comprehensive standard of care led to a 15.9 and 16.0 point decrease on the Montgomery-Åsberg Depression Rating Scale (MADRS), a tool used to assess the severity of depressive symptoms, in the two trials at 24 hours after the first dose of study medication. This compared to a reduction of 12.0 and 12.2 points in the placebo plus comprehensive standard of care group. The comprehensive standard of care included initial hospitalization, a newly initiated or optimised oral antidepressant and twice-weekly treatment visits for four weeks, during which patients received SPRAVATO 84 mg or placebo nasal spray.
Both the SPRAVATO and placebo groups continued to improve between four hours and 25 days, with 41 per cent and 43 per cent of the SPRAVATO plus comprehensive standard of care group achieving clinical remission of depression (minimal or no symptoms) compared with 34 per cent and 27 per cent in the placebo groups, by the end of the double-blind period, in the two trials, respectively.
Gerard Sanacora, Director, Yale Depression Research Program, Co-Director, Yale New Haven Hospital Interventional Psychiatry Service, and esketamine clinical trial investigator said, “The clinical trials supporting this new indication provide compelling evidence that esketamine may offer clinicians a new way to provide support to patients quickly in the midst of an urgent depressive episode and help set them on the path to remission.”
In the two Phase 3 trials, improvement in the severity of suicidality at 24 hours was measured using a standardised global scale. The treatment difference between the two groups was not statistically significant on this key secondary endpoint. Both SPRAVATO and placebo in combination with a comprehensive standard of care showed a similar reduction on this measure.
The safety profile observed in the trials was consistent with previous studies of SPRAVATO in treatment-resistant depression (TRD), adding to the established body of safety and efficacy evidence. The most common side effects included dissociation (feeling disconnected from yourself, your thoughts, feelings, space and time), dizziness, sedation (sleepiness), increased blood pressure, hypoesthesia, vomiting, euphoric mood and vertigo.
With this new indication, SPRAVATO can be prescribed to treat depressive symptoms in two MDD subpopulations of adults with high unmet need: TRD, which the FDA approved on March 5, 2019, and MDD with acute suicidal ideation or behaviour.
A full course of treatment for the new indication is twice weekly for four weeks, after which evidence of therapeutic benefit should be evaluated to determine the need for continued treatment.
Once SPRAVATO is determined as an appropriate treatment option, in accordance with the REMS, patients will be treated at a certified treatment centre trained to administer the medicine and address their needs.