Investigational New Drug Clearance Given to R-Ketamine

The FDA has given Investigational New Drug clearance for a clinical drug-drug interaction study of R-ketamine (PCN-101).

The US Food and Drug Administration (FDA) has given Investigational New Drug (IND) clearance to Atai Life Sciences to conduct a clinical drug-drug interaction study of R-ketamine (PCN-101). Atai intends to initiate the study early this year through its platform company, Perception Neuroscience, as part of the clinical development program for R-ketamine.1

PCN-101 is a single isomer of ketamine and pharmacologically a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. It belongs to a new class of glutamate receptor modulators with the potential for rapid acting antidepressant activity and antisuicidal effects.

In nonclinical depression model studies in rodents, research suggests that R-ketamine could possess longer durability and a potentially more favorable safety and tolerability profile than S-ketamine. An open-label clinical study also demonstrated rapid, durable response and limited dissociative adverse effects in treatment-resistant depression (TRD) patients after a single intravenous dose.

“TRD represents a large percentage of people with severe, difficult to treat depression who have failed to sufficiently respond to at least 2 different antidepressant treatments,” said Terence Kelly, PhD, CEO of Perception Neuroscience. “We believe that PCN-101 has the potential to offer a differentiated therapeutic effect, in terms of both efficacy and ease of administration, for clinicians and patients, as a potentially rapid-acting antidepressant. We look forward to progressing its clinical development.”

This clinical DDI trial will advance alongside an existing phase 2a proof-of-concept trial in TRD, which was recently initiated in Europe.2 Furthermore, Atai will run a bioavailability study in 2022, designed to bridge the IV formulation to a subcutaneous formulation of PCN-101, supporting the potential for at-home self-administration.

“We see great promise in PCN-101 as a potentially rapid-acting anti-depressant with a more favorable safety and tolerability profile than S-ketamine, which could enable at-home use,” said Florian Brand, CEO and Co-Founder of Atai Life Sciences. “With today’s IND clearance, we are excited to continue assessing the therapeutic potential of PCN-101 in the US, where, like elsewhere in the world, many patients struggle with treatment-resistant depression and desperately need innovative therapeutic options.”

References

1. Atai Life Sciences announces FDA Investigational New Drug (IND) Clearance for PCN-101 R-ketamine program. News release. January 12, 2022. https://www.atai.life/2022/01/12/atai-life-sciences-announces-fda-investigational-new-drug-ind-clearance-for-pcn-101-r-ketamine-program

2. Perception Neuroscience initiates Phase 2a study of PCN-101 (R-ketamine) for treatment resistant depression. News release. September 14, 2021. Accessed January 12, 2022. https://ir.atai.life/news-releases/news-release-details/perception-neuroscience-initiates-phase-2a-study-pcn-101-r