Back in January, atai Life Sciences released results for its most advanced program: PCN-101 (using R-Ketamine for Treatment-Resistant Depression). Unfortunately for patients and investors, the results “did not meet its primary endpoint of a statistically significant change from baseline”. 

Atai said it would “continue to support Perception’s development of PCN-101 through an additional IV-to-subcutaneous bridging study. In parallel, atai continues to work with Perception Neuroscience to explore strategic partnership options.”

Late yesterday, atai announced results from Perception Neuroscience’s Phase 1 intravenous-to-subcutaneous bridging study of PCN-101 (R-ketamine). The Phase 1 study assessed the safety, tolerability, and pharmacokinetic profile of PCN-101 delivered subcutaneously compared to PCN-101 delivered intravenously (the previous trial with lackluster results was done intravenously).

The study compared a 60mg IV dose — to 60mg, 90mg and 120mg of subcutaneously (SQ) PCN-101, looking at safety, tolerability and PK profiles. Highlights from the study:

• 120mg of SQ PCN-101 resulted in an approx doubling of drug exposure while maintaining approximately the same maximum concentration (Cmax) as the 60mg IV dose.
• PCN-101 was generally well-tolerated with no serious adverse events reported. 
• Sedation and dissociation rates at 120mg SQ dose were significantly lower than the previous PCN-101 trial (60mg IV) and intranasal Spravato (S-ketamine).

“While recognizing the limitations of this small bridging study and cross-trial comparisons, this safety and tolerability profile compares favorably to that of Spravato … Collectively, we believe these data support the concept of at-home use of PCN-101 in future studies.”

See the full press release below.

atai Life Sciences Announces Results from the Phase 1 IV-to-Subcutaneous Bridging Study of PCN-101 (R-Ketamine)

NEW YORK and BERLIN, Aug. 08, 2023 (GLOBE NEWSWIRE) — atai Life Sciences (NASDAQ: ATAI) (“atai”), a clinical-stage biopharmaceutical company aiming to transform the treatment of mental health disorders, announced results from Perception Neuroscience’s Phase 1 intravenous-to-subcutaneous bridging study of PCN-101 (R-ketamine).

The Phase 1 open-label, 4-period crossover study assessed the safety, tolerability, and pharmacokinetic profile of 60mg, 90mg and 120mg of PCN-101 delivered subcutaneously (“SQ”) as compared to 60mg of PCN-101 delivered intravenously (“IV”). The study enrolled 16 healthy volunteers, each into one of four sequences of administration.

The study was designed to inform dosing regimens of the new subcutaneous formulation that may optimize the therapeutic index—the balance of safety, tolerability, and efficacy—of PCN-101 in future studies, thereby supporting further exploration of the potential of R-ketamine as a rapid acting anti-depressant for at-home use.

Pharmacokinetic (PK) analysis indicates that 120mg of PCN-101 delivered SQ resulted in an approximate doubling of drug exposure (AUC) while maintaining approximately the same maximum concentration (Cmax) as the 60mg IV dose.

Further, PCN-101 was generally well-tolerated with no serious adverse events reported. At the 60mg IV dose, rates of sedation and dissociation were consistent with prior studies of PCN-101 at this dose-level. Encouragingly, at the highest SQ dose of 120mg, rates of sedation (defined as MOAA/S1 score <5) and dissociation (defined as CADSS2 total score >4 and change from baseline >0) were each 14%.

While recognizing the limitations of this small bridging study and cross-trial comparisons, this safety and tolerability profile compares favorably to that of Spravato, for which rates of sedation and dissociation have been reported to be in the ranges of 50-61% and 61-69%3, respectively, in prior studies. In addition, rates of sedation and dissociation were similar to those seen in the placebo arms of both the prior Phase 2 study of PCN-101 and the Spravato clinical trials in depression. Collectively, we believe these data support the concept of at-home use of PCN-101 in future studies.

atai continues to work with Perception Neuroscience to explore strategic partnership options.
1. Modified Observer’s Assessment of Alertness and Sedation 2. Clinician Administered Dissociative State Scale 3. SPRAVATO (esketamine) [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc 2020.

About atai Life Sciences

atai is a clinical-stage biopharmaceutical company aiming to transform the treatment of mental health disorders and was founded as a response to the significant unmet need and lack of innovation in the mental health treatment landscape. atai is dedicated to 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 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.

About Perception Neuroscience

Perception Neuroscience is a biopharmaceutical company committed to developing therapies for neuropsychiatric diseases. Perception’s mission is to provide substantially more effective treatment solutions to serious psychiatric disorders. The company is a majority-owned subsidiary of atai Life Sciences.

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.

The post atai Life Sciences Announces Results of New Phase 1 Study of PCN-101 (R-Ketamine) appeared first on Microdose.

Read More