The industry has been waiting for these results. atai Life Sciences Phase 2a study of PCN-101 (R-ketamine) for treatment-resistant depression was the most anticipated milestone of the second part of 2022, and today we finally received the news.
Unfortunately, the results were not as good as anticipated.
According to the company’s press release, PCN-101 “did not meet its primary endpoint of a statistically significant change from baseline in participants’ MADRS (Montgomery-Åsberg Depression Rating Scale) score at 24 hours compared to placebo.”
So while PCN-101 “demonstrated signals of efficacy across all timepoints out to two weeks” — showing that the compound does have some positive effects on patient results — it did not show significant differences in efficacy from the placebo group.
Disappointing news for investors and industry advocates who’d been waiting for a shot of good news after a tough 2022.
This does not mean the end of atai’s PCN-101 program, as the drug was generally well-tolerated, with “rates of sedation and dissociation comparable to placebo.”
What’s next? A revised Phase 2 trial? Focus on another condition other than treatment-resistant depression? Time will tell. In the meantime the company comments were brief:
atai will further evaluate the PCN-101 data in more detail over the next weeks and will work with its subsidiary Perception Neuroscience to explore next steps, including but not limited to seeking strategic partnership options.
The markets were anticipating this news and have not handle it well. atai stock was down over 40% in early trading.
NEW YORK and BERLIN, Jan. 06, 2023 (GLOBE NEWSWIRE) — atai Life Sciences (NASDAQ: ATAI) (“atai” or “the Company”), a clinical-stage biopharmaceutical company focused on mental health, announced that, while PCN-101 (R-ketamine) demonstrated signals of efficacy across all timepoints out to two weeks, Perception Neuroscience’s Phase 2a clinical trial did not meet its primary endpoint of a statistically significant change from baseline in participants’ MADRS (Montgomery-Åsberg Depression Rating Scale) score at 24 hours compared to placebo.
The Phase 2a proof-of-concept trial was a two-week, randomized, double-blind, placebo-controlled multi-center study assessing the safety, tolerability and efficacy of a single IV administration of PCN-101. 102 TRD patients were enrolled across three arms – 30mg, 60mg and placebo.
On the primary endpoint of MADRS at 24 hours, the mean change from baseline was -15.3 for PCN-101 60mg compared to -13.7 for placebo (-1.6 pbo-adj; p-value 0.5). However, the single 60mg dose of PCN-101 showed an efficacy signal at each timepoint over the 2-week timeframe of the study.
Key secondary endpoints included a proportion of patients defined as responders, meaning patients who experienced 50% improvement from baseline in MADRS, and a proportion of patients in remission, defined as a total MADRS score of less than 10. Despite seeing greater response and remission rates in the 60mg arm, the trial did not meet statistical significance at any timepoint on these secondary measures.
PCN-101 was generally well-tolerated with rates of sedation and dissociation comparable to placebo.
“We thank all the patients, families, caregivers, and investigators for their support and participation in the PCN-101 Phase 2a trial,” said Florian Brand, CEO and Co-Founder of atai.
PCN-101 demonstrated an encouraging safety profile and signals of efficacy across all timepoints despite not achieving statistical significance on the primary endpoint. atai will further evaluate the PCN-101 data in more detail over the next weeks and will work with its subsidiary Perception Neuroscience to explore next steps, including but not limited to seeking strategic partnership options.
PCN-101 Phase 2a Study Design
The Phase 2a proof-of-concept trial was a randomized, double-blind, placebo-controlled multi-center study assessing the safety, tolerability and efficacy of IV PCN-101 (R-ketamine) in 102 patients with TRD across three arms. These patients – all of whom had previously failed at least two rounds of antidepressants – received a single IV dose of either placebo, 30 mg, or 60 mg of PCN-101 adjunctively to their existing treatment regimen.
Patients were assessed for a change in depressive symptomatology using the Montgomery-Åsberg Depression Rating Scale (MADRS) at intervals over 14 days, with the primary endpoint at 24 hours post-dose. Dissociation and sedation were measured using the Clinician-Administered Dissociative States Scale (CADSS) and the Modified Observer’s Alertness/Sedation Scale (MOAA/S), respectively.
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. It is developing PCN-101 (R-ketamine) for the treatment of TRD. In March 2021, the company announced a collaboration and licensing agreement with Otsuka Pharmaceutical Co., Ltd. for rights in Japan to PCN-101. Perception Neuroscience is a majority-owned subsidiary of atai Life Sciences.
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.