Esketamine nasal spray found superior to quetiapine extended-release in resistant depression in phase 3 trial

Esketamine nasal spray was found superior to to quetiapine extended-release (XR) in adults with treatment-resistant major depressive disorder, according to topline results of a phase 3b trial that compared the short- and long-term efficacy, safety of the two.

"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.1,4 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. 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 weeks1-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

Reference:

Reif A. et al., Esketamine nasal spray improves short‑ and long‑term outcomes compared with quetiapine extended release in patients with treatment resistant depression: First results from ESCAPE‑TRD, a randomised, multi‑centre phase IIIb clinical trial. Presented at DGPPN 2022, November 23-26. Poster P-01-04.