How Cybin is Shifting Psychedelic Clinical Trial Execution and Regulatory Strategy

In the dynamic field of mental health, Cybin is pioneering psychedelic therapies. Amir Inamdar, Cybin’s Chief Medical Officer, discusses their innovative clinical trials and their regulatory posture. This interview explores the design of Cybin’s studies, the complexities of placebo effects, and the rigorous standards set by the FDA.

Moe: Can you detail your study designs, including sample size and endpoints? How do these reflect a paradigm shift in mental health treatment?

arm study using a dose-ranging approach to gather comprehensive efficacy data. This design not only adheres to regulatory standards but also aims to address the significant unmet needs in mental health treatment, particularly for those who do not respond to conventional therapies.

Moe: How does placebo work in psychedelic studies, given the noticeable effects? How do you address functional unblinding and expectancy effects?

The challenge of placebo in psychedelics isn’t new. Many drugs, like antidepressants, have noticeable effects that can unblind studies. The key issue with psychedelics is the combination of functional unblinding and high expectations. While blinding is often ineffective in CNS studies, long-term effects beyond 12 weeks are less likely to be placebo-driven. Our studies follow FDA guidance, focusing on long-term efficacy to address these concerns. For instance, our EMBRACE study uses a dose-ranging approach to mitigate expectancy effects, providing a robust framework to evaluate true efficacy versus placebo effects. This approach is crucial in ensuring that the observed benefits are genuinely attributable to the treatment rather than psychological biases.

Moe: How are you designing your trial to minimize observer bias, especially considering the intense experiences associated with psychedelics?

We employ independent remote blind raters to assess patients, removing investigator bias. During dosing sessions, we limit exposure to study staff to prevent functional unblinding. This includes keeping session notes confined and ensuring that only necessary personnel are aware of treatment details, maintaining the integrity of the study. By using remote raters who are completely blind to the treatment conditions, we ensure that the assessments are unbiased and purely based on the patient’s condition. This method is particularly important in psychedelic trials, where the subjective nature of the experience can easily influence both patient and observer perceptions.

Moe: What measures are you taking to ensure the safety of your medical product, particularly regarding cardiac monitoring and abuse potential?

We’ve conducted extensive preclinical studies, including cardiac slice studies, and found no issues with our compound. The concern with 5-HT2B receptor activity is primarily with repeated dosing, which doesn’t apply to our treatment regimen. Following FDA guidelines, we also collect comprehensive data on abuse liability to ensure a thorough understanding of our product’s safety profile. This includes monitoring for any signs of euphoria, dissociation, or hallucinations, which are critical in assessing the potential for abuse. Our comprehensive approach ensures that we meet all regulatory requirements while prioritizing patient safety.

Moe: How are you planning to demonstrate the long-term durability of the treatment effect in your trials? Are there specific strategies you employ to ensure robust data collection?

After completing the 12-week double-blind treatment, patients can enter a long-term extension study lasting up to a year. This allows us to assess the durability of treatment effects, monitor safety, and gather additional data on treatment response and relapse. By offering this extended follow-up, we can observe how long the benefits of the treatment last and how patients respond to subsequent treatments if needed. This approach provides valuable insights into the long-term efficacy of our treatments and aligns with FDA guidance on demonstrating sustained benefits.

Moe: What’s your take on the FDA’s panel rejection of MDMA-assisted therapy, and how does it impact your approach? How do you ensure that your trials meet the heightened scrutiny?

The rejection highlights the need for rigorous adherence to FDA guidance, particularly regarding psychotherapy standards and safety data. We use a framework called Embark, based on evidence-based practices, to ensure compliance. This approach and proactive engagement with the FDA position us well to meet regulatory expectations. We ensure that our session monitors are well-trained and that our methodologies are aligned with empirically supported treatments. This proactive stance not only addresses the concerns raised by the FDA but also ensures that we are prepared for any regulatory challenges.

Moe: Do you think psychedelic trials are held to a different regulatory standard compared to traditional CNS trials? How do you navigate these standards to ensure successful trial outcomes?

Interestingly, I don’t think the standards are different. The FDA requires demonstration of efficacy and durability, similar to other CNS drugs. The agency has been proactive in providing guidance specific to psychedelics, which is crucial given the unique challenges of these trials. While the standards aren’t heightened, the FDA’s clarity is invaluable in navigating this complex field. Our breakthrough therapy designation allows us regular interactions with the FDA, ensuring that we remain aligned with their expectations and can address any concerns promptly. This ongoing dialogue is essential in maintaining the integrity and success of our clinical programs.