The drug showed a significant, clinically meaningful and fast-acting improvement in depression symptoms compared to an intranasal placebo.
Janssen Research & Development a Johnson & Johnson company, has been working for several years on developing ketamine, a notable animal tranquilizer and drug-of-abuse with a street name of Special K, into a treatment for severe depression.
The company released data from a Phase II trial of its intranasal esketamine in patients with treatment-resistant depression. The results are both promising and concerning.
The drug showed a significant, clinically meaningful and fast-acting improvement in depression symptoms compared to an intranasal placebo. All the participants in the study were also taking oral antidepressants, the standard of care.
The positive effects were seen in all three dosages, some showing the effects as quickly as two hours after receiving esketamine. Improvement was observed at a week at all three doses, which were administered twice weekly.
There were 126 patients in the trial. The results were also dose-dependent, with the highest dose being about twice as effective as the low dose, although all were deemed clinically significant.
Which sounds great. But, John Carroll, with Endpoints News, wrote, “The bad news: Among the side effects was ‘perceptual changes/dissociative symptoms,’ which ran at more than twice the rate seen in the placebo arm. One in four of the patients taking the drug experienced dissociative symptoms. Sedation was another common symptom. The dissociative symptoms occurred shortly after dosing and generally resolved after a couple of hours. In other words, the Phase II version of this drug still carries risks linked to Special K.”
Treatments for depression, especially selective serotonin reuptake inhibitors (SSRI) such as Zoloft and Prozac, can be inconsistent across the population. Meaning, basically, that treating complex nervous system and behavioral disorders is complicated.
Carroll wrote, “Ketamine works on NMDA receptors, and that in turn has led to a surge of new drug development programs, including a late-stage effort at Allergan after that company acquired Naurex for $560 million upfront. Sage as also attracted widespread interest in its own approach for depression.”
Esketamine is now being evaluated in Phase III clinical trials for treatment-resistant depression and for patients with major depressive disorder who are at imminent risk for suicide. In addition, there is a Phase II trial for adolescents with major depressive disorder at imminent risk for suicide.
Esketamine received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) in November 2013 for treatment-resistant depression. It got it again in August 2016 for major depressive disorder with imminent risk for suicide.
Major depressive disorder affects almost 300 million people globally, an enormous market. About one third of patients do not respond to treatment with currently available antidepressants.
“The results of this study reinforce the potential of eskatamine as a treatment for patients with treatment-resistant depression and support further clinical research, providing hope for people in need,” said Husseini Manji, Janssen’s global head of Neuroscience Therapeutic Area, in a statement. “If approved by the FDA, esketamine would be one of the first new approaches to treat refractory major depressive disorder available to patients in the last 50 years.”
