On July 6, Seelos Therapeutics announced that the first patient has been dosed in the second part of their registrational, double-blind, placebo-controlled study of SLS-002 (intranasal racemic ketamine) for acute suicidal ideation and behavior (ASIB) in patients with major depressive disorder (MDD).
There is a significant unmet need within the MDD market for pharmacotherapies that can demonstrate rapid antidepressant effects, particularly for patients with severe MDD requiring hospitalization. Studies have shown that the prevalence of suicide in patients with MDD ranges from 2.2% for mixed inpatient/outpatient populations to 8.6% for those who have been previously hospitalized for suicidality. This compares to a suicide prevalence of less than 0.5% in the general population. Not only do the currently available products show antidepressant effects only after several weeks of treatment, but most antidepressants also have a boxed warning for increased risk of suicidal thinking and behavior in children, adolescents, and young adults. Therefore, there is also an unmet need for therapies to treat ASIB. In the first part of the study, SLS-002 showed significant improvement in depressive symptoms measured by a greater than 50% decrease in Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline at 24 hours compared to placebo.
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. Although Spravato was a breakthrough treatment for ASIB, risks of sedation, dissociation, and abuse and misuse mean it is only available through a restricted program, the Risk Evaluation and Mitigation Strategy (REMS) Program. Additionally, Spravato’s high cost of therapy and requirement for two hours of patient observation after administration will 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. Of the late-stage products, AXS-05, which is 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 $1.3B by 2029.