Is Psilocybin Really a Miracle Drug? Compass Pathways Releases Phase 2B Trial Results

Something strange happened yesterday. Psychedelics unicorn Compass Pathways released data for the largest clinical trial ever conducted of a psilocybin drug. Not only did the drug seem to work, but the heavily anticipated data were “breathtaking” in the words of Compass’ CEO. Immediately, the company’s publicly traded shares dropped 16%. Including the day prior, it was more like 28%.

Why did this happen? There may be a couple of related factors. First, the trial data contained some problematic features, which I’ll address below. Second, and more interestingly, unrealistic expectations likely played a role. Many people believe that psychedelic drugs are or could be miraculous– that these drugs have inherent capacity to cure a variety of physical, mental and spiritual ills. Compass’ 2B trial suggests otherwise. It suggests that Compass may simply have contrived a useful therapy.

Backing up a bit, the disorder targeted by Compass is treatment-resistant depression. The therapy regime is a single dose of synthesized psilocybin (COMP360), paired with psychological support from specially trained therapists. I’ve explained before that treatment-resistant depression is a formidable disease. Around 100 million individuals suffer from this affliction worldwide; and “treatment resistant” means that nothing works– not antidepressants, not psychological counseling, not even grisly procedures like electroconvulsive therapy. Compass is trying to slay a giant here.

The company ran a controlled, randomized, double-blind study over 10 countries, 22 sites and 209 patients. It was the FDA gold standard, no doubt. The data reveal: 1) that a single, 25mg dose showed a significant reduction in severity of depression symptoms after three weeks; but 2) a single, 10mg dose did not show a significant difference in depression symptoms over the same period.

That first prong is the “breathtaking” part; the second prong is mildly disappointing from this non-clinician’s perspective. But there was also a third key finding, and it likely dinged the stock: 12 of the 233 patients experienced “treatment-emergent serious adverse events” (TESAEs). Some of the TESAEs were relatively mild, like headache, fatigue and insomnia. Other TESAEs included suicidal behavior, intentional self-harm, and suicidal ideation.

Compass rightly notes that all of these TESAEs are “regularly observed in a treatment-resistant depression group” and that this group is a tremendously challenging population. Three people died of suicide in the Spravato trials, for example, and Symbax also comes with grave warnings. (Spravato and Symbax are the only FDA approved drugs for treatment-resistant depression.) But analysts, investors and others who believe in the power of classic psychedelics to cure depressive disorders were likely dismayed to see these results. The hype was just so extraordinary.

FDA will parse the Compass data and the agency seems likely to shepherd COMP360 into Phase 3 trials. That alone is impressive: most drugs never even make it to Phase 2, and when they do, only 31% progress to Phase 3. Ultimately, it seems more likely than not that COMP360 will eventually win full approval, and we’ll have a psilocybin drug in the US Pharmacopeia not long after the MAPS MDMA drug makes the cut. (For a high-level overview of the FDA approvals process, see our post on MDMA here.)

In the meantime, Compass’ data will continue to foster discussion and mixed reviews, and ripple throughout the industry. All the big psychedelics stocks slid on Tuesday’s news: Mindmed dropped 10%; Atai Life Sciences dropped 8% and Cybin lost 1%. Because Compass is a bellwether of sorts, its success or failure may also influence the prospects of the myriad of psychedelics drugs being pushed into FDA purview, and the companies that stand behind them. Compass’ success or failure may even have collateral implications for non-FDA regimes, like state-sanctioned psilocybin therapy in Oregon.

Finally, these trial results will also be of strong interest to people who take issue with Compass’ particular brand of psychedelic capitalism, starting with its for-profit conversion several years ago and extending through its aggressive intellectual property “moating” strategy. Plenty of people would like to see Compass fail, not for what the company is trying to do, but for how it’s going about it.

In a vacuum, the COMP360 effort and data are remarkable. The fact that a single psilocybin dose reduced depression symptoms three weeks out is remarkable! But expectations were sky high and the atmospherics are intense. It may be time to recalibrate expectations on psilocybin, LSD, ayahuasca, MDMA and everything else in the FDA context. Maybe a better expectation is for a few safe and effective psychedelic drugs, rather than something miraculous.

For more on Compass and COMP360, check out the blog posts below. For more on psilocybin and psychedelics drugs generally, our extensive archive can be found here.

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FDA, Psychedelics, News