J&J bags a second breakthrough tag for planned depression blockbuster

Johnson & Johnson ($JNJ) has received a second breakthrough therapy designation from the FDA for its antidepressant esketamine. It’s for an indication of major depressive disorder with imminent risk for suicide; the prior designation is for treatment-resistant depression, which the pharma received in November 2013.

Esketamine could offer another option to treat depression, which is underserved and has seen scant innovation in decades. It’s an N-methyl-D-aspartate (NMDA) receptor antagonist--and an isomer of the generic anesthetic and notorious party drug ketamine. The intranasal formulation offers fast-acting benefits, unlike standard oral treatment approaches.

J&J has high expectations for esketamine, which it listed last year among the more than 10 late-stage products that it expects could become blockbusters with over $1 billion in sales. The candidate was the only neurology candidate in this list, all of which the pharma expects could be approved before 2020. Neuroscience is one of J&J’s five core therapeutic areas.

“What we found was again spectacular results where patients who were refractory to most antidepressants when they go on esketamine within days, their improvement in mood is dramatic and somewhat unpredictable,” said William Hait, J&J’s Janssen Global Head of Research & Development on a conference call in early May describing data on the candidate. “The duration of the effect is much longer than one might have predicted from the half-life of the drug. So very rapid improvement in mood, not the weeks and sometimes even months to take SSRI or tricyclic. So very rapid and long duration.”

Phase III data for the treatment-resistant depression indication is expected in late 2017. The Phase II data to support the breakthrough designation in major depressive disorder with imminent risk for suicide was reported in May at the Society of Biological Psychiatry conference.

Hait added, “The study was done in patients who come to the emergency room, they've attempted suicide or about to attempt and someone rescues them. They get admitted to the hospital for standard treatment plus or minus esketamine. And what we saw again, within days, a dramatic improvement in the mood of these patients and a decrease in suicide ideology.”

Ketamine is already used off-label to treat depression patients, a practice that’s increasing according to a recent Leerink note based on interviews with a trio of depression physician specialists.

And J&J is not alone in targeting NMDA for depression. Allergan ($AGN) is also developing intravenous rapastinel, which is in Phase III and oral AGN-241660, which is in Phase II, both of which are NMDA modulators. Rapastinel also received breakthrough designation from the FDA in January.

The specialists interviewed by Leerink viewed rapastinel and esketamine as the most promising NMDA modulators to treat depression due to Phase II data showing a rapid onset of action and limited psychotomimetic side effects; the latter is an issue with off-label ketamine use.

- here is the release

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