In the first placebo-controlled efficacy study completed to date exploring a short-duration psychedelic for depression, intravenous (IV) N,N-Dimethyltryptamine (DMT)—SPL026—with supportive therapy for the treatment of major depressive disorder (MDD), met the primary endpoint and demonstrated a statistically significant and clinically relevant reduction in depressive symptoms at 2-weeks post-dose as compared with placebo.
The phase 2a trial included 2 stages, and enrolled 34 participants with moderate/severe MDD, who were dosed with a 21.5 mg IV infusion of SPL026 that resulted in a 20- to 30-minute psychedelic experience. In the blinded, randomized, placebo-controlled phase, the primary endpoint was to assess the efficacy of a single dose of SPL026 with supportive therapy (N=17) versus placebo with therapy (N=17) at 2-weeks post-dose. Subsequently, all study participants were enrolled in an open-label phase in which they received a single dose of SPL026 with supportive therapy and were followed-up for 12 weeks.
“The results are exciting for the field of psychiatry. We now have the first evidence that SPL026 DMT, combined with supportive therapy, may be effective for people suffering from MDD,” said David Erritzoe, MD, a clinical psychiatrist at Imperial College London and chief investigator of the phase 1/2a study. “For patients who are unfortunate to experience little benefit from existing antidepressants, the potential for rapid and durable relief from a single treatment, as shown in this trial, is very promising.”
Efficacy was assessed using the Montgomery-Asberg Depression Rating scale (MADRS). Independent raters who were not present for dosing and were blinded to overall treatment assessed MADRS. Compared with placebo, SPL026 with supportive therapy demonstrated a statistically significant and clinically relevant reduction in depressive symptoms 2-weeks, with a -7.4 point difference in MADRS (p=0.02). Analysis of key secondary endpoints demonstrated a rapid onset of antidepressant effect 1-week post-dose, with a statistically significant difference in MADRS score between the active and placebo groups of -10.8 (p=0.002).
“We are pleased that a significant number of patients benefited from the treatment in our trial. SPL026 with supportive therapy was shown to have a significant antidepressant effect that was rapid and durable, with a remission rate of 57% at 3 months following a single dose of SPL026,” said Carol Routledge, Chief Medical and Scientific Officer of Small Pharma. “It was encouraging to see that SPL026 demonstrated a favorable safety and tolerability profile in MDD patients in this study, consistent with our phase 1 study. The results are clinically meaningful and enable us to progress into an international multi-site phase 2b study where we seek to further explore the efficacy and safety profile of SPL026 in a larger MDD patient population.”
George Tziras, the Chief Executive Officer of Small Pharma had this to say on the data: “MDD affects the lives of hundreds of millions of people worldwide. The scale of the unmet need indicates the importance of investigating alternative new treatments. Our goal is to develop proprietary, scalable, and reimbursable short-duration psychedelics with supportive therapy to address this need. I am delighted with our top-line results, which demonstrate proof-of-concept for SPL026 and provide encouraging support for our broader portfolio. I want to thank each patient who took part in this trial, as well as their families, the trial investigators, the employees of the trial sites and everyone who has supported the successful completion of this study.”
1. Small Pharma reports positive top-line results from phase IIa trial of SPL026 in major depressive disorder. News release. Edmonton Journal. January 25, 2023. https://edmontonjournal.com/globe-newswire/small-pharma-reports-positive-top-line-results-from-phase-iia-trial-of-spl026-in-major-depressive-disorder