Seelos Therapeutics has recently announced that the first patient has been dosed in the second part of its registrational study of SLS-002 (intranasal racemic ketamine) for acute suicidal ideation and behavior (ASIB) in patients with major depressive disorder (MDD). If approved SLS-002 would become only the second product approved specifically for ASIB, after Johnson & Johnson’s rapid-acting Spravato (esketamine) was approved for moderate-to-severe MDD patients with ASIB in 2020 in the US. However, Spravato is only available through a restricted program, due to risk of sedation and disassociation, which will hinder its uptake, says GlobalData, a leading data and analytics company.

Philippa Salter, Neurology Analyst at GlobalData, comments: “There is a significant unmet need within the MDD market for pharmacotherapies that can demonstrate rapid antidepressant effects, in particular for patients with severe MDD requiring hospitalization including those with ASIB. In part one of the study, SLS-002 showed significant improvement in depressive symptoms at 24 hours compared to placebo.”

Salter continues: “Although Spravato was a breakthrough treatment for ASIB, its high cost of therapy, and requirement for two hours of patient observation after administration will also limit its uptake. As such, GlobalData forecasts that Spravato will generate global sales of approximately $383m by 2029. As a related compound, and with the same intranasal route of administration, it is possible that SLS-002 will face similar issues to Spravato. However, in a small, randomized trial intranasal ketamine caused minimal dissociative effects, which, if replicated in larger trials, would give SLS-002 an advantage over Spravato.”

Given the issues surrounding Spravato, significant opportunity remains for fast-acting antidepressants to enter the market, and several late-stage products have demonstrated the potential to fulfill this unmet need: Sage Therapeutics/Biogen’s zuranolone (SAGE-217), Axsome Therapeutics’ AXS-05 (bupropion + dextromethorphan), and Relmada Therapeutics’ REL-1017. Although these products are not in development for ASIB, if they are able to demonstrate strong efficacy for MDD, it is possible that a label expansion could be sought in the future.

Salter adds: “Of the late-stage products, AXS-05, expected to launch later this year in the US, is the most promising product based on its strong efficacy results in Phase III trials. GlobalData anticipates that Axsome Therapeutics’ AXS-05 will have the potential to become a blockbuster drug, and could generate global sales of approximately $1.3bn by 2029.”