J&J Wins Phase III in Major Depressive Disorder

Johnson & Johnson (J&J) recently announced a significant breakthrough with their experimental drug, seltorexant, in treating major depressive disorder (MDD) accompanied by insomnia symptoms. The late-stage Phase III clinical trial demonstrated that seltorexant met all primary and secondary endpoints, showing substantial improvements in both depressive symptoms and sleep disturbances.

Seltorexant functions as a selective antagonist of the orexin-2 receptor. The trial results highlighted a statistically significant and clinically meaningful reduction in depressive symptoms, based on the Montgomery-Asberg Depression Rating Scale (MADRS) total score, by day 43. Additionally, patients who had previously responded inadequately to SSRI/SNRI antidepressants alone showed marked improvements in sleep quality. According to J&J, the drug exhibited a favorable safety profile, with adverse event rates comparable between the treatment and placebo groups.

These findings were showcased at the American Society of Clinical Psychopharmacology (ASCP) annual meeting in Miami. J&J adopted a precision-based approach for this trial, targeting MDD patients who also experience insomnia, rather than employing a broader, all-inclusive method. This strategy addresses a significant issue, as roughly 60% of MDD patients suffer from insomnia despite receiving standard oral antidepressant therapy.

Andrew Krystal, a psychiatry professor at the University of California, San Francisco Weill Institute for Neurosciences, emphasized the potential impact of seltorexant. He noted that the drug could address a major unmet need by enhancing treatment outcomes and quality of life for patients experiencing both depression and insomnia.

In addition to seltorexant, J&J is advancing another MDD candidate, a kappa-opioid receptor antagonist, currently in Phase III trials. This drug targets MDD patients suffering from anhedonia, a condition characterized by an inability to experience pleasure or interest in life.

J&J's targeted-patient strategy is gaining momentum as they aim to improve the traditionally low success rates of psychiatric drugs. This precision approach is mirrored by biotech company Alto Neuroscience, which uses biomarkers such as cognitive tests and brain scans to identify suitable patients for their MDD treatments.

At the ASCP meeting, J&J also presented data from a Phase IV study of their nasal spray, Spravato. This ketamine-based drug, already approved for treatment-resistant depression (TRD) and MDD with suicidal thoughts or actions, is being tested as a monotherapy for TRD. The study showed significant improvements in depressive symptoms within 24 hours of the first dose, which were sustained through four weeks of treatment.

However, according to Graig Suvannevejh, a senior biopharma and biotech equity research analyst at Mizuho Americas, the delivery method and required safety monitoring for Spravato pose challenges. Patients must visit a doctor’s office to receive the nasal spray and remain under observation for two hours post-administration. Despite these hurdles, Suvannevejh believes Spravato remains a valuable option for patients with difficult-to-treat depression.

Johnson & Johnson's recent advancements in MDD treatment underscore their commitment to addressing specific patient needs with precision-based therapies. By targeting subsets of MDD patients with tailored approaches, J&J hopes to achieve higher success rates and improve the overall quality of life for those struggling with this complex mental health disorder.