Perception Neurosciences, an atai Life Sciences subsidiary, Announces Additional Analyses from the Phase 2a Trial of PCN-101 (R-ketamine) at the ASCP 2023 Annual Meeting
New York, NY
June 9, 2023
Additional analyses of a Phase 2a study on PCN-101 (R-ketamine) were reported at ASCP.
A prespecified analysis showed differences in US and EU cohorts with the US subgroup demonstrating clinically meaningful improvement in depression scores out to 2 weeks after a single IV 60mg dose (p = 0.03).
A single 60 mg IV dose of PCN-101 led to 43% of patients reaching remission (p=0.20, secondary endpoint) assessed at 24 hrs post-infusion.
PCN-101 was generally well-tolerated with no serious adverse events and acceptable safety profile. No significant differences in sedation or dissociation vs. placebo were observed.
Perception Neurosciences (“Perception”), an atai Life Sciences subsidiary, announced that further analyses from the Phase 2a clinical trial of PCN-101 (R-ketamine) were presented at this year’s American Society for Clinical Psychology (ASCP) 2023 annual meeting. The poster presentation was delivered on May 31, 2023 by Dr. Maju Mathews, Perception’s Chief Medical Officer. The randomized, placebo-controlled Phase 2a trial evaluated the efficacy and safety of a single IV administration of 30 and 60mg of PCN-101 (R-ketamine) in 102 patients with treatment-resistant depression (TRD).
In January 2023, results were announced from the Phase 2a proof-of-concept study. While the results did not reach statistical significance on the primary endpoint, PCN-101 demonstrated an encouraging safety profile and signals of efficacy.
The additional analyses presented at ASCP provide greater detail on the efficacy endpoints, including at the 60mg dose where efficacy trends were observed starting at 2 hours post-dose and at each timepoint over the 2-week study. In addition, at the 60mg dose, a pre-specified analysis looking at regional differences showed that PCN-101 demonstrated a clinically relevant improvement at US sites but not at EU sites. At US sites, the placebo-adjusted change in MADRS was -4.77 at 24-hours (p=0.32), -9.2 at Day 8 (p=0.15), and -13.12 at Day 15 (p=0.03). Key secondary endpoints included the proportion of patients reaching remission, defined as a total MADRS score of less than 10. While the trial did not meet statistical significance at any timepoint on this secondary measure, a trend toward a higher remission rate at the 60mg dose was observed. At 24 hours post-dose, 43% of patients receiving 60 mg of PCN-101 achieved a total MADRS score of less than 10 as compared to 27% receiving placebo (p=0.22). These results persisted out to Day 14.
Additionally, PCN-101 was generally well-tolerated with rates of dissociation and sedation comparable to placebo. Dissociation, as measured by the Clinician-Administered Dissociative States Scale (CADSS), showed a score greater than 4 in 23%, 36% and 27% of patients on 60mg PCN-101, 30mg PCN-101 and placebo, respectively. In addition, sedation, as measured on the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale, showed a score less than 5 in 34%, 27% and 34% in patients receiving 60mg PCN-101, 30mg PCN-101 and placebo, respectively with the lowest score being 3 at any timepoint. There were also no significant differences in blood pressure between PCN-101 and placebo.
“While not statistically significant, in a disease like major depression, where only half the studies are successful, the efficacy signal seen with a single 60 mg dose, along with the favorable safety profile, provide hope for PCN-101 as a potential rapid acting antidepressant.” said Dr. Mathews. “Existing therapies for TRD have a high side effect burden and involve a lot of time commitment for the patient and providers, contributing to stigma. Developing an effective alternative would significantly improve the treatment experience and provide an additional treatment for this chronically underserved population.”
“We remain committed to developing treatments for patients suffering from TRD,” said Terence Kelly, CEO of Perception Neuroscience. “We are currently conducting a Phase 1 relative bioavailability bridging study to assess subcutaneous formulations of PCN-101 compared to IV. This IV-to-subcutaneous bridging study will potentially inform dosing regimens of the new subcutaneous formulation and may optimize the therapeutic index—the balance of safety, tolerability and efficacy—of PCN-101 in future studies. I am deeply grateful to the Perception team, our partners (especially the atai team) and our trial participants, for supporting this important next step.”
This Phase 1 open-label study is designed to assess the safety, tolerability, and pharmacokinetic profile of 60mg, 90mg and 120mg of PCN-101 delivered subcutaneously as compared to 60mg of PCN-101 delivered intravenously (IV). The trial will enroll approximately 16 healthy volunteers across the four cohorts and is expected to be completed in the middle of 2023.
About Perception Neuroscience, Inc
Perception Neuroscience is a New York City-based clinical-stage biopharmaceutical company committed to the mission of providing more effective treatment solutions for serious psychiatric disorders. The company is a majority-owned subsidiary of atai Life Sciences.
The company’s lead asset, PCN-101, is a single isomer of ketamine and belongs to a new generation of glutamate receptor modulators with the potential for rapid-acting antidepressant activity and anti-suicidal effects. Pharmacologically, PCN-101 is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. Depression model studies in rodents suggest that R-ketamine could possess more durable effects than S-ketamine and a more favorable safety and tolerability profile.
About atai Life Sciences
atai Life Sciences is a clinical-stage biopharmaceutical company aiming to transform the treatment of mental health disorders. Founded in 2018 as a response to the significant unmet need and lack of innovation in the mental health treatment landscape, atai is dedicated to acquiring, incubating, and efficiently developing innovative therapeutics to treat depression, anxiety, addiction, and other mental health disorders.
By pooling resources and best practices, atai aims to responsibly accelerate the development of new medicines across its companies to achieve clinically meaningful and sustained behavioral change in mental health patients.
atai's vision is to heal mental health disorders so that everyone, everywhere can live a more fulfilled life. For more information, please visit www.atai.life.