After Lykos MDMA rejection, atai's oral psychedelic shows promise

Following the recent setback faced by Lykos Therapeutics after the FDA rejected its psychedelic-based therapy for PTSD, another company, atai Life Sciences, is forging ahead with its own experimental treatment. On Tuesday, atai Life Sciences announced promising preliminary outcomes from a Phase Ib trial of its psychedelic oral treatment, VLS-01. The company aims to advance this drug into Phase II trials for treatment-resistant depression (TRD) by the end of the year.

VLS-01 is atai's proprietary oral transmucosal film of N,N-dimethyltryptamine (DMT), the principal active ingredient in ayahuasca, a traditional hallucinogenic brew from South America. The formulation consists of a thin film placed on the inside of the cheek, where it gradually dissolves.

In the Phase Ib study, atai confirmed that VLS-01 reached peak plasma concentration within 30-45 minutes, inducing a short psychedelic experience. The subjective effects generally dissipated within two hours post-administration. The study included 17 healthy participants, each receiving a single intravenous dose of DMT followed by three different doses of atai’s buccal film: 20 mg, 60 mg, 120 mg, or 160 mg, with a 28-day washout period between administrations.

According to atai, 13 of the 14 participants in the 120-mg cohort achieved Subjective Intensity Rating Scale (SIRS) scores above seven. They described the experience as "psychologically meaningful" and reported "increased levels of self-reflection." The treatment also showed a favorable safety profile, with all adverse events being mild or moderate and mostly resolving on the day of dosing. Common side effects included headache, dissociation, euphoric mood, and nausea. No adverse events related to blood pressure, heart rate, or suicidality were observed.

This promising readout comes at a time when the field of psychedelic-based medicines is trying to recover following the FDA's complete response letter to Lykos' midomafetamine (MDMA) therapy, commonly known as ecstasy. The FDA's letter, coupled with the retraction of three MDMA studies due to ethical concerns, has spotlighted challenges in study design, especially around functional unblinding and expectation bias in psychedelic drug trials. The FDA has requested Lykos to conduct a new Phase III trial, which the company acknowledges will take several years to complete.

Srinivas Rao, co-CEO of atai, stated that if the preliminary findings for VLS-01 can be replicated in Phase II, the compound "could become a best-in-class treatment for TRD, one that offers a well-tolerated, convenient oral dosing and a short psychedelic experience that fits into the two-hour in-clinic commercial paradigm established within interventional psychiatry."

The company anticipates top-line data from the planned mid-stage trial to be available around the end of 2025.