Compass Pathways Reports Second Positive Phase 3 Trial for Psilocybin in Depression

Compass Pathways announced results from COMP006, its second Phase 3 trial using the company's formulation of synthetic psilocybin, COMP360, for treatment-resistant depression. According to the company, participants who received two 25mg doses of COMP360 showed a "highly statistically significant and clinically meaningful reduction in symptom severity" compared to participants who received 1mg placebo doses of the drug.

Participants' depression symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). On average, participants who received the two 25mg doses of COMP360 showed a 3.8 point decrease in MADRS scores compared to the placebo group at six weeks into the trial's treatment period. The scale is a 60-point measure where bigger scores signal more severe depression symptoms.

These results were nearly identical to those of COMP005, the company's first Phase 3 trial, in which participants received just one dosing session. In that trial, initially reported in June 2025, the difference between the 25mg group versus a group that received an inert placebo was 3.6 points.

Compass said almost 40% of participants in the higher dose arm experienced a "clinically meaningful reduction" in depression scores at that time point. Among those patients, researchers saw a "statistically significant rapid onset" of the drug's effect, starting the day after administration and lasting through the six weeks. The company expects 26-week data to become available in the third quarter.

The second trial was twice as large as the first. Researchers evaluated two doses of COMP360 against a far smaller dose that acted as a control group. Such a design can help address "unblinding," a well-documented concern with psychedelics studies where participants deduce what arm they've been assigned to based on whether they're experiencing the test drug's mind-altering properties.

Compass has relied on an independent board of experts to assess safety across both experiments. This board views the safety data seen thus far as "consistent" with earlier studies. No new, unexpected or concerning findings have arisen, including no evidence of a "clinically meaningful imbalance" between treatment arms in suicidality.

The company has asked to meet with the Food and Drug Administration to discuss a "rolling" submission of its synthetic form of psilocybin sometime in between October and December. Should the FDA accept that application and ultimately grant approval, the compound would become the first "classic" psychedelic cleared for the U.S. market.

CEO Kabir Nath stated: "This is a remarkable achievement for the field of psychiatry — especially in the TRD population, where proving benefit has historically been extraordinarily challenging. These data strengthen our conviction in the highly differentiated profile for COMP360."

Compared with the company's Phase 2b results, published in The New England Journal of Medicine in 2022, the Phase 3 outcomes were less impressive: in the earlier study, the difference in MADRS scores between the 25mg group and 1mg group was, on average, 6.6 points, nearly twice that of what the company reported for both of these Phase 3 trials.

Compass modified its definition of "clinically meaningful" in COMP006's results compared to earlier studies. In this most recent announcement, Compass defined a meaningful response as a greater than 25% decrease in MADRS score, but the company has previously used 50% as their criteria in reporting data from pilot studies and its Phase 2B study results.

Company shares spiked more than 50% higher Tuesday morning, to just under $9 apiece, with the release of data from the second trial. Compass's stock price has increased by some 30% since the company announced their results. Results from the first experiment came last summer and, though positive, didn't live up to investor expectations, leading to a major stock sell off and Compass losing nearly half of its market value.

The director of Massachusetts General Hospital's Center for Neuroscience of Psychedelics said the data "probably meets the bar for approval," though "it doesn't shout out to you that this is miraculous."