Janssen Pharmaceutical said that the esketamine nasal spray along with the comprehensive standard of care (SOC) has met the primary efficacy endpoints of two phase 3 trials featuring adult patients with a major depressive disorder.
The ASPIRE I and II trials evaluated the efficacy and safety of esketamine nasal spray in 465 patients with the moderate-to-severe major depressive disorder who have active suicidal ideation with intent. The late-stage trials showed a rapid reduction of depressive symptoms in the patients treated with Janssen’s nasal spray.
Reduction in depressive symptoms at 24 hours after the first dose, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), was the primary efficacy endpoint on both the trials.
Esketamine nasal spray 84mg plus SOC delivered clinically meaningful and statistically significant superiority compared to placebo plus SOC in a rapid reduction of symptoms of major depressive disorder across the two trials, said Janssen.
Likewise, Janssen’s nasal spray and SOC combination was generally well-tolerated with no new safety signals. Its safety profile was consistent across the two late-stage trials and also with previous studies of the nasal spray in patients with treatment-resistant depression.
Said to be a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, esketamine works differently than presently available therapies for major depressive disorder, said the Johnson & Johnson company.
Janssen research and development clinical research senior director Carla Canuso said: “These data are particularly important because patients with major depressive disorder presenting with active suicidal ideation with intent constitute a psychiatric emergency that requires immediate intervention.
“Although currently available antidepressants are effective for many patients, their onset of effect can take four to six weeks, offering limited benefit to those in urgent need.”
In the ASPIRE I and II trials, esketamine plus comprehensive SOC and placebo plus comprehensive SOC showed improvement in the severity of suicidality, which was their secondary endpoint. This was measured by the revised Clinical Global Impression of Severity of Suicidality (CGI-SS-R) at 24 hours following the first dose.
The treatment difference between the two patient arms on the secondary endpoint was not significant statistically, said Janssen. This could be because of the substantial beneficial effects of comprehensive SOC used in the trials, said the company.
Esketamine nasal spray in conjunction with an oral antidepressant was approved by the US Food and Drug Administration in March 2019 for the treatment of treatment-resistant depression (TRD).