SPRAVATO®▼ (esketamine) nasal spray data from the phase 3b ESCAPE-TRD study demonstrate superior efficacy compared to quetiapine extended-release in treatment-resistant major depressive disorder1

SPRAVATO^®▼ (esketamine) nasal spray data from the phase 3b ESCAPE-TRD study demonstrate superior efficacy compared to quetiapine extended-release in treatment-resistant major depressive disorder¹

First findings from the study support the short- and long-term use of SPRAVATO^® (esketamine) nasal spray in adults living with treatment-resistant major depressive disorder in achieving remission and remaining relapse free¹

High Wycombe, UK, 23 November 2022 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results from ESCAPE-TRD, a long-term, comparative, randomised, open-label phase 3b clinical trial designed to evaluate the short- and long-term efficacy, safety and tolerability of flexibly dosed SPRAVATO^® (esketamine nasal spray [NS]) compared with quetiapine extended-release (XR), both in combination with a continuing selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI), in adults with treatment-resistant major depressive disorder (TRD).¹ The findings, presented today at the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) Congress, showed that esketamine NS met its primary endpoint, demonstrating superior efficacy in achieving remission at Week 8 compared to quetiapine XR.¹ The study also met its key secondary endpoint, demonstrating that not only did significantly more participants treated with esketamine NS compared to quetiapine XR achieve remission while on study treatment at Week 8, they also remained relapse free up to Week 32.¹

“Achieving remission and remaining relapse free are major milestones in the treatment of depression and are especially challenging in TRD, where patients have not responded to previous therapies,” said Professor Andreas Reif, Principal Investigator for the ESCAPE-TRD trial and Head of Department, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy at University Hospital Frankfurt, Germany.^* “The ESCAPE-TRD findings showed that esketamine nasal spray enabled a significantly greater percentage of patients to achieve remission at Week 8 and remain relapse free in the longer term up to Week 32 compared to quetiapine extended-release. This provides further evidence for the use of esketamine nasal spray in this difficult-to-treat population and offers hope for the millions of people affected by TRD.^2,3”

The trial evaluated 676 adults with TRD, randomised to receive either esketamine NS (n=336) or quetiapine XR (n=340), both in combination with a continuing SSRI/SNRI.⁴  TRD was defined as non-response to at least two consecutive adequately dosed treatments (including the ongoing treatment) during the current depressive episode.^1,5

The primary endpoint assessed rates of remission⁺ while on study treatment at Week 8 between the two trial arms and demonstrated that significantly more participants achieved remission in the esketamine NS arm compared to the quetiapine XR arm (27.1% vs. 17.6%, respectively; p=0.003).¹

The key secondary endpoint of the trial was remaining relapse free while on study treatment at Week 32, after achieving remission at Week 8.¹ Significantly more participants achieved remission at Week 8 with no relapse at Week 32 in the esketamine NS arm compared to the quetiapine XR arm (21.7% vs. 14.1%, respectively; p=0.008).¹

In addition, remission rates continued to increase in both arms after the primary endpoint at Week 8 with a significantly greater proportion of patients in remission at Week 32 in the esketamine NS arm versus the quetiapine XR arm (55% vs 37% ; p<0.001).¹

“People living with TRD experience significant disruption and impairment to their lives, and there is an urgent and ongoing need to identify therapies to effectively address what can be a devastating condition,” said Dr. Tamara Werner-Kiechle, EMEA Therapeutic Area Lead, Neuroscience and Pulmonary Hypertension, Janssen-Cilag GmbH, part of the Janssen Pharmaceutical Companies of Johnson & Johnson. “We are pleased to see that esketamine nasal spray has been demonstrated to be effective and well-tolerated versus a strong augmentation comparator treatment in enabling people to achieve the goals of achieving remission and remaining relapse free up to 32 weeks – important and meaningful milestones in treating TRD. Today’s findings from the ESCAPE-TRD trial are an important step towards helping people who have not responded to multiple previous treatment cycles, being able to get the respite they need.”

The most common (≥10%) treatment-emergent adverse events (TEAEs) observed in the esketamine NS arm were dizziness (46.7%), nausea (29.3%), dissociation (28.1%), headache (24.6%), vertigo (18.9%), somnolence (15.0%), dysgeusia (12.0%), paresthesia (11.1%) and vomiting (10.8%).¹ These results are consistent with safety data collected in previous studies.^1,6 In the quetiapine XR arm the most common TEAEs were somnolence (23.2%), weight increase (12.5%) and headache (12.8%).¹ Serious TEAEs were observed in 5.1% of participants in the quetiapine XR arm and 5.7% in the esketamine NS arm.¹ Treatment discontinuation occurred in 23.2% of participants in the esketamine NS arm compared to 40.3% in the quetiapine XR arm, and was mainly due to a lack of treatment efficacy (8.3% for esketamine NS vs. 15.0% for quetiapine XR), adverse events (4.2% for esketamine NS vs. 11.5% for quetiapine XR) or participant refusal of further treatment (8.3% for esketamine NS vs. 8.5% for quetiapine XR).¹

* Professor Andreas Reif has been a paid consultant to Janssen; he has not been paid for contributing to this press release.

+ Remission was defined as Montgomery-Asberg Depression Rating Scale [MADRS] total score ≤10¹.