FDA Breakthrough Therapy Designation Granted to Novel Psychedelic Molecule CYB003 for Major Depressive Disorder


At 4 months, 75% of participants achieved remission and no longer showed signs of depression symptoms in a phase 2 clinical trial.

The FDA has granted breakthrough therapy designation (BTD) to CYB003 (Cybin), a deuterated psilocybin analogue that is being investigated as an adjunctive treatment for major depressive disorder (MDD) in clinical trials. The BTD by the FDA is based on data from the phase 2 trial of CYB003 for MDD, which showed patients experienced robust and sustained improvement in their MDD symptoms at 4 months, with 75% of participants who received 2 doses at 16 mg achieving remission and no longer showing signs of depression.

Key Takeaways

  1. Breakthrough Therapy Designation Significance: The breakthrough therapy designation (BTD) indicates that CYB003 meets a significant unmet need for patients with major depressive disorder (MDD). BTD provides benefits such as expedited review pathways and enhanced engagement with the FDA, potentially reducing drug development timelines.
  2. Efficacy and Safety Data: Data from the phase 2 trial of CYB003 for MDD showed robust and sustained improvements in depression symptoms, with approximately 75% achieving remission after 4 months. CYB003 demonstrated significant efficacy, with a substantial reduction in MADRS total scores across both 12 mg and 16 mg dosage levels. Importantly, CYB003 exhibited a favorable safety profile with predominantly mild or moderate adverse events (AEs) and no occurrences of serious AEs or suicidal ideation.
  3. Potential Impact on Treatment Landscape: Current standard treatments for MDD, such as SSRIs, have limitations in efficacy, remission, and response rates. CYB003 shows promise as a potential significant treatment option, with efficacy data surpassing that of currently FDA-approved antidepressants. The potential of CYB003 to address these challenges is underscored by the BTD and the favorable efficacy and safety data from the phase 2 trial. The designation allows for an accelerated regulatory path forward, highlighting the anticipation for CYB003's phase 3 trial, which aims to further evaluate its safety and efficacy in a larger patient population.

One of the benefits provided by the BTD is an expedited review pathway after completion of a phase 3 trial and submission of a new drug application to the FDA. Additionally, BTD allows the FDA to be more involved in the phase 3 trial design, with the potential of getting guidance that can reduce drug development timelines.

“This designation provides for a streamlined review process and enhanced engagement with the FDA. With the robust durability data from our phase 2 study in hand, we are ready to move forward expeditiously,” said Doug Drysdale, chief executive officer of Cybin, in a press release. “We are grateful for the opportunity to accelerate the development and regulatory review process that this designation affords, as we prepare to advance CYB003 toward a phase 3 pivotal trial around mid-year.”

BTD is reserved for drug candidates that meet significant unmet need for patients. MDD, which affects over 300 million people globally, is currently treated with antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). More than 43 million Americans take antidepressants, 70% of whom are treated with SSRIs. However, up to two-thirds of patients with MDD do not achieve remission with initial SSRI treatment, supporting CYB003’s potential to act as a significant treatment option for patients. Based on the phase 2 data, CYB003 demonstrated an improvement in MDD symptoms that is more significant than current FDA-approved antidepressants.

“Currently available standard treatments for MDD can be limited in efficacy, remission, and response rates, presenting challenges for patients and mental health practitioners alike. CYB003 may have potential to address these challenges, and with the FDA’s [BTD], the regulatory path forward is accelerated,” Maurizio Fava, MD, chair of the Department of Psychiatry and Psychiatrist-in-Chief at Massachusetts General Hospital, said in the press release.

Four-month efficacy data for CYB003 demonstrated robust and sustained improvements in symptoms of depression across 2 dosage levels—both the 12 mg and 16 mg—which demonstrated significant efficacy, with an approximate 22-point reduction from baseline in the MADRS total score in both dosing cohorts. Notably, following 2 doses of 16 mg, approximately 75% of patients were classified as responders, showing a 50% or greater improvement in MADRS scores. Additionally, a substantial portion of patients experienced remission from depression, with 60% achieving remission on the 12 mg dose and 75% on the 16 mg dose. Remission was assessed based on achieving a MADRS score of 10 or below after 2 doses.

MADRS is a 10-item scale designed to measure overall severity of MDD symptoms. It is widely used in clinical trials, as it is accepted by regulatory authorities as an effective measure of symptoms of MDD. In the MADRS, scoring items can range from sadness of mood, reduction in sleep and appetite, to difficulties in concentration, anhedonia, and negative and suicidal thoughts, with a total score ranging from 0 to 60. Typical MADRS score ranges are as follows in terms of severity of symptoms: 0-6 is normal; 7-19 is mild; 20-34 is moderate; and more than 34 is severe depression. In the phase 2 CYB003 study, mean baseline total scores on the MADRS before treatment were 31.4 to 33.7 in the active group and 30.8 in the placebo group.

In terms of safety and tolerability, CYB003 also exhibited favorable profiles in the phase 2 study. CYB003 was well tolerated, with no occurrences of serious adverse events (AEs). The AEs that did arise were predominantly mild or moderate in intensity, indicating a manageable AE profile. Importantly, there were no instances of suicidal ideation or behavior noted among participants in the trial, further underscoring the safety of CYB003. Additionally, the absence of discontinuations due to AEs suggests that patients were able to tolerate the medication well over the course of the study period.

“It is truly remarkable that at 4 months the participants experienced a sustained reduction and incremental improvement in depression symptoms,” said Drysdale in the press release. “Impressively, the mean reduction from baseline in the MADRS total score was approximately 22 points at 4 months (compared to a mean reduction of 14 points vs placebo and 17 points from baseline at 3 weeks). This is highly encouraging, especially for patients who have not responded to existing treatment options. We look forward to initiating our phase 3 trial, which we anticipate will be an international, multisite study to further evaluate the safety and efficacy of CYB003 capsules in a larger MDD patient population.”


Cybin Receives FDA Breakthrough Therapy Designation for its Novel Psychedelic Molecule CYB003 and Announces Positive Four-Month Durability Data in Major Depressive Disorder. News Release. March 13, 2024. Accessed March 14, 2024. https://www.businesswire.com/news/home/20240313731043/en

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