Janssen's Spravato (Esketamine) Nasal Spray Approved by European Commission for Treatment-Resistant Depression

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Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, recently announced that the European Commission has approved Spravato (esketamine) nasal spray, in combination with a selective serotonin reuptake inhibitor (SSRI) or a serotonin and norepinephrine reuptake inhibitor (SNRI), for the treatment of adult patients with treatment-resistant depression (TRD).

Patients are considered to have treatment-resistant depression (TRD) if they fail to respond to at least two different antidepressant medications during the current moderate-to-severe depressive episode. Notably, Spravato is the first antidepressant with a novel mechanism of action approved in Europe in the past 30 years.

Major Depressive Disorder (MDD) affects approximately 40 million people in Europe. For these patients, the primary goal of treatment is to alleviate depressive symptoms and ultimately achieve remission. However, about one-third of patients with MDD do not respond to current therapies.

This approval is based on data from a clinical program in patients with treatment-resistant depression (TRD), in which more than 1,600 patients received Spravato. The program comprised five Phase III studies, including three short-term studies, one randomized withdrawal and maintenance-of-efficacy study, and one long-term safety study. The data demonstrated that, in adult patients (aged 18–64 years), Spravato combined with a newly initiated oral antidepressant reduced depressive symptoms to a greater extent than a newly initiated oral antidepressant plus placebo, with onset of effect as early as Day 2. Approximately 70% of patients treated with Spravato achieved a ≥50% reduction in symptoms. Furthermore, approximately half of the patients achieved remission by the end of the 4-week short-term studies. Among patients who achieved a stable response or remission, continuing treatment with Spravato plus an oral antidepressant reduced the risk of relapse by 70% and 51%, respectively, compared with continuing monotherapy with an oral antidepressant.

In five Phase III and one Phase II clinical trials, Spravato demonstrated a favorable benefit-risk profile, sustained efficacy, and no new safety concerns were observed over a period of up to one year. Among patients with treatment-resistant depression (TRD) treated with Spravato, the most commonly observed adverse events included dizziness, nausea, headache, somnolence, vertigo, decreased appetite, hypoesthesia, and vomiting. These side effects were generally mild to moderate in severity, transient, occurred on the day of administration, and typically resolved within 2 hours.

Spravato’s active ingredient, esketamine, is an N-methyl-D-aspartate (NMDA) receptor antagonist. This medication features a novel and unique mechanism of action that differs from other currently marketed antidepressants.

Major depressive disorder (MDD) has a profound impact on patients and their loved ones. Many patients have tried various treatments, which typically take 4–6 weeks to become effective. Spravato, administered via nasal spray with rapid onset and sustained efficacy, will offer a welcome treatment option for patients.

In the United States, Spravato was approved in March 2019, in combination with an oral antidepressant, for the treatment of adult patients with treatment-resistant depression (TRD). Currently, a supplemental new drug application for Spravato is under review by the FDA for the treatment of adult patients with major depressive disorder (MDD) who have acute suicidal ideation or behavior, to rapidly reduce depressive symptoms.

Reference Source: SPRAVATO (Esketamine) Nasal Spray Approved in Europe for Adults with Treatment-Resistant Major Depressive Disorder