Psilocybin, the psychoactive core of magic mushrooms, could be headed toward late-stage trials in treatment-resistant depression (TRD), pending the results of a soon-to-start phase IIb study. London-based Compass Pathways Ltd. has received permission from the FDA and additional regulators to run a dose-ranging study in up to 216 patients across Europe and North America. The trial, which seeks to enroll 216 patients at 12 to 15 research sites, will begin in the U.K. later this month and is expected to read out toward the end of 2019.
"Depression is the leading cause of ill-health and disability worldwide," said George Goldsmith, the company's co-founder and chairman. "Treatment-resistant depression affects more than 100 million people. It is a huge unmet need and the trial will teach us more about how this new approach might address it," he said. Goldsmith leads the company alongside his wife, the company's co-founder and chief medical officer, Ekaterina Malievskaia.
The phase IIb study will compare three doses of psilocybin with psychological support and will use a set of standard, validated patient-reported outcomes (PRO) during screening to establish the treatment-resistant depression diagnosis and again afterward, to assess the impact of the therapy, company spokeswoman Tracy Cheung told BioWorld.
The exact doses and PRO instruments the trial will employ were unclear on Wednesday. However, an early version of the company's protocol contemplated assessment of 1 mg, 10 mg and 25 mg of the psychoactive drug and using the Montgomery-Asberg Depression Rating Scale to both screen and review psilocybin-related changes in participants' mental states. It also contemplated an evaluation of the safety and tolerability of psilocybin in participants with TRD based on adverse events, changes in vital signs, and suicidal ideation or behavior as measured by the Sheehan Suicidality Tracking Scale.
If successful, the study will be followed by phase III trials, Compass said, studies that would be expected to compare the optimal dose to either placebo or standard of care.
In July, Compass' team reported having manufactured two batches of psilocybin, the equivalent of more than 20,000 doses of 25 mg to support late-stage clinical trials. A large portion of the doses will be used for stability testing to meet regulatory requirements, the company said. But an additional part of its stash will be provided for free to members of the European College of Neuropsychopharmacology through its Medicines Chest program in an effort to support independent psilocybin research.
Meanwhile, Compass employees are helping run a 16-week study of the "Effects of psilocybin on cognition and emotional processing" at the Institute of Psychiatry, Psychology & Neuroscience at King's College London, in partnership with the University of Zurich, Switzerland and Cambridge Cognition Holdings plc. The study will randomize 90 healthy volunteers to receive placebo, 10 mg or 25 mg of psilocybin, administered simultaneously in up to six participants. It will explore the drug's effects on empathy, executive function, memory, attention and cognitive flexibility.
Earlier research has suggested that coupling psilocybin with psychological support provides immediate and sustained reduction in depression for patents, following a single treatment, Cheung said. One such study, an open-label feasibility trial in 12 patients with moderate-to-severe, unipolar, treatment-resistant major depression, was led by academics at the Imperial College London and documented in The Lancet in July 2016. Results of the trial showed that, relative to baseline, depressive symptoms were markedly reduced 1 week (p=0·002) and 3 months (p=0·003) after treatment with a 25 mg dose of the serotonin receptor agonist. Additional studies of psilocybin in various indications ranging from anxiety to addiction have unfolded in U.S. academies, including the University of Wisconsin, Johns Hopkins, and the University of California, Los Angeles — work supplementing a recent resurgence of less clinically rigorous experimentation among individuals such as the author Michael Pollan, who documented his experience with psilocybin in a recent book, "How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence."
Compass, which was founded in 2016, has raised more than £25 million (US$32.3 million) to date from a range of investors. It has received seed investment from Apeiron Investment Group, Thiel Capital, and Galaxy Investment Partners. Apeiron is the family office of Christian Angermayer, the co-founder of Ribopharma AG, a company that merged with Alnylam Pharmaceuticals Inc. in 2003. Peter Thiel is a famed tech investor who has made an increasing number of bets of life sciences companies in recent years. (See BioWorld Today, July 8, 2003.)