Following the news (5^th March 2019) that the US FDA approved Johnson & Johnson’s nasal spray antidepressant, Esketamine,

Alessio Brunello, Pharma Analyst at GlobalData, a leading data and analytics company, offers his view:  

“Esketamine, developed by J&J, is the first major depression disorder (MDD) treatment, with a novel mechanism of action, to be approved by the FDA in the US market in many years and a new option of treatment for patients with depression who do not respond to existing therapies, known as treatment-resistant depression (TRD), making a significant impact on the treatment of many MDD patients who have been unresponsive to current antidepressant therapy.

“Esketamine is the S-enantiomer of ketamine, an NMDA receptor antagonist with a rapid onset of antidepressive effects and is formulated as an intranasal spray, a preferable formulation. This is a less invasive mode of administration, an important factor in the potential commercial success of any MDD therapy. There undoubtedly would be higher patient and prescriber acceptance of such a drug formulation of Esketamine compared to IV, leading to greater drug uptake and improved adherence.

“Esketamine is a first-in-class antidepressant, however, it will face direct competition from Allergan’s rapastinel (GLYX-13), which is in Phase III of clinical development but is not expected to launch in the US until 2021, after Esketamine. Rapastinel also acts through NMDA receptor modulation, but binds to the glycine site of this receptor, and therefore, exerts a different biochemical effect, and is thought to potentially have an improved safety profile compared to Esketamine. Allergan hopes its project might not have the same psychomimetic effects as Esketamine as also the need to monitor patients and restrict activities after rapastinel will be less than the requirements for Esketamine.

“J&J is also testing esketamine as a treatment for people with depression who are at risk of suicide, and Topline results are expected to release in 2019.

“The MDD market has many unmet needs, a large number of MDD patients do not respond to the available treatments and products used for the treatment of depression are associated with significant side effects and risk factors, which directly affect compliance. None of the previous marketed products for depression can demonstrate rapid antidepressant effects, and most of the products take weeks to show effectiveness. The need for fast-acting therapies is more pressing in patients with the severe form of the disease and these new therapies can help to meet this unmet need.”