Dextromethorphan Hydrobromide Hydrate

Major depressive disorder (MDD) is characterised by characterised by depression and inability to feel pleasure. Credit: Justin Paget via Getty Images. Johnson & Johnson’s (J&J) nasal spray Spravato (esketamine) has received a label expansion, now approved as a monotherapy treatment for major depressive disorder (MDD) in adults who do not respond to two oral antidepressants. The US Food and Drug Administration’s (FDA’s) decision makes Spravato the first-ever standalone treatment for adults with treatment-resistant depression. Initially approved in 2019 for use alongside oral antidepressants, this label expansion follows a priority review from the FDA. The approval was based on data from the Phase IV TRD4005 study (NCT04599855), which demonstrated a significant reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) total score within 24 hours after the initial dose, with effects sustained for at least four weeks. Spravato’s safety profile aligns with existing data for oral antidepressants, with no new safety concerns detected. The standard-of-care for MDD typically involves selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) as first-line treatments, often in combination with psychotherapy. However, these therapies can take weeks to exert an effect, and many patients do not respond adequately, leading to a need for innovative alternatives. Spravato targets the brain’s N-methyl-D-aspartate (NMDA) receptor. Unlike traditional MDD therapies that usually take weeks to work, J&J says this drug delivers rapid action. MDD is a severe, chronic mood disorder characterised by depression, inability to feel pleasure, guilt, low energy, and impairments in essential functioning. The global MDD market, valued at $8.8bn in 2019, is expected to grow to $16.2bn in 2029, according to a GlobalData report. GlobalData is the parent company of Pharmaceutical Technology. GlobalData notes that growth will be driven by the rising patient share of newly approved drugs, including J&J’s Spravato. Generating $689m in 2023 – nearly double its 2022 revenue of $374m – the drug’s sales are projected to reach $2.6bn by 2030. Another key contributor to this growth is Axsome Therapeutics’ Auvelity (dextromethorphan and bupropion). The company submitted a new drug application for Auvelity to the FDA for the treatment of MDD, which was accepted under priority review in April 2021. The FDA then approved Auvelity extended-release tablets in August 2022. Axsome’s drug is forecast to generate $1.9bn by 2030. With researchers looking for alternative treatments for mental health conditions, psychedelics have gained investor attention in recent years after demonstrating success in clinical trials. Psilocybin, a psychedelic prodrug compound found in more than 200 species of fungi, is currently in a Phase III programme for treatment-resistant depression with Compass Pathways .

Axsome Therapeutics on Monday reported data for two Phase 3 studies in Alzheimer’s-related agitation, saying one trial succeeded while the other failed. Researchers looked at whether an Axsome program called AXS-05 could both delay episodes of agitation relapse and induce a significant change in patients’ agitation symptoms. The first trial, which examined delayed relapse, achieved its primary endpoint. The second, measuring symptoms on a 29-item systemic assessment, did not. Even with the mixed results, Axsome said it expects to file for FDA approval in the second half of 2025. The company said three of four Phase 3 trials testing AXS-05 in Alzheimer’s-related agitation met their primary endpoints and were statistically significant. Axsome’s stock price $AXSM was down about 9% in early trading on Monday. AXS-05 is an extended-release tablet combining the cough suppressant dextromethorphan and the antidepressant bupropion (sold under the brand name Wellbutrin). It’s designed to target NMDA receptors. The FDA previously approved AXS-05 as a rapid-acting depression drug, which Axsome sells as Auvelity. Axsome described the trial that succeeded as a “withdrawal trial” that administered AXS-05 to all patients for one year before randomizing them into a double-blinded study period. Once participants were randomized, those taking AXS-05 were 3.6 times less likely to experience a relapse episode compared to placebo, good for a p-value of p=0.001. Additionally, the hazard ratio was 0.276, and the program achieved key secondary endpoints, Axsome said. According to the company, the trial that failed saw trends in favor of AXS-05, but there was not enough separation from placebo in improving symptoms to be deemed statistically significant. After five weeks, AXS-05 improved patients’ assessment scores by 13.8 points, compared to 12.6 points for those on placebo.