Cybin Inc., a Toronto-based biopharmaceutical company, has initiated a Phase 3 pivotal trial of deuterated psilocin (CYB003) for major depressive disorder (MDD), marking a significant step forward in the development of psychedelic-based treatments. This progress comes amid increased scrutiny from the FDA regarding clinical data requirements and safety protocols for psychedelic drugs.
Addressing FDA Concerns
Doug Drysdale, CEO of Cybin, noted that the company has benefited from the evolving knowledge base at the FDA, particularly following the setbacks experienced by Lykos Therapeutics and Compass Pathways. Cybin has incorporated learnings from these experiences into its Phase 3 program to align with FDA expectations. "We really had to dig into the details and understand the consequences of the Lykos decision," said Drysdale. "The timing kind of worked out for us, and we were able to incorporate all of those concerns and learnings into our Phase 3 program, and to align with FDA."
Key items that the FDA is focusing on include trial timing, endpoints, and patient population. According to Drysdale, the FDA prefers a short primary endpoint, such as six weeks, followed by 12 weeks of double-blinded, placebo-controlled data. The agency also emphasizes the use of a psychedelic-naïve population to control for expectation bias.
Enhanced Safety Measures
To address concerns about blinding, Cybin monitors patients for four to six hours during clinical trials, using eye masks and curated playlists. While monitors can often discern whether a patient is having a psychedelic experience, raters who assess the patient's depressive score before and after the session remain blinded to this information.
Cybin is also recording all trial sessions and using both manual and AI-driven auditing to ensure facilitators and monitors adhere to the study protocol. This includes monitoring for inappropriate behavior or any attempts to influence patients, thereby minimizing bias and ensuring patient safety.
Leveraging Breakthrough Therapy Designation
Cybin's CYB003 has received breakthrough therapy designation, which Drysdale says has significantly enhanced the company's interactions with the FDA. "I've never been involved with a breakthrough therapy treatment before, and the difference in FDA interactions is marked, it's completely different," he noted. This designation facilitates more substantive discussions and input from the FDA, allowing Cybin to refine its clinical program.
Infrastructure and Market Landscape
The growing use of Johnson & Johnson’s Spravato (esketamine), a ketamine-derived product for treatment-resistant depression and MDD, has helped expand the infrastructure needed for administering psychedelic medicines. Spravato, which is expected to reach blockbuster status with potential annual sales of $5 billion, has established itself in approximately 4,500 treatment centers. Cybin anticipates that CYB003, if approved, could be integrated into this existing infrastructure.
Trial Design and Patient Population
Cybin's Phase 3 trial involves two studies. The first will see 110 patients take two 16-milligram doses three weeks apart, while 110 take placebos. In the second, three 110-person groups will either take 16-mg doses, eight-mg doses or placebos. There will be an initial six-week study, after which patients will be followed for a year. Those whose depression returns or doesn’t improve can get additional doses.
With these measures in place, Cybin aims to navigate the evolving regulatory landscape and bring a novel treatment option to the millions of people affected by major depressive disorder.
