â— Phase 2 Proof-of-Concept study in TRD patients resistant to standard antidepressants suggests a positive trend in efficacy.
â— Potential first-in-class oral prolonged-release formulation of ketamine, KET01, suggests a larger improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) scores at 15 days compared to placebo.
â— Improvement in MADRS scores shown at seven days suggests the rapid onset of efficacy.
â— Safety: no treatment-related serious adverse events with only placebo-level dissociative side-effects reported.
HMNC Brain Health ("HMNC'' or the "Company"), a global clinical-stage biopharmaceutical company pioneering the development of personalized therapies in psychiatry, together with Develco Pharma, a company specializing in the development and manufacture of orally administered modified, prolonged & chrono release drugs today announced promising top-line results from the Phase 2 Proof-of-Concept investigator-initiated trial of its oral prolonged-release formulation of ketamine (KET01) in Treatment-Resistant Depression (TRD).
The trial suggests a positive trend in efficacy based on the primary endpoint clinical data: After 15 days, the highest dose of 240 mg/day of KET01 was associated with a larger improvement on the Montgomery-Åsberg Depression Rating Scale (MADRS) compared with placebo (Δ=-4.99, p=0.1499). In addition, KET01 appears to be a safe and well-tolerated antidepressant, with substantially limited dissociative side effects and scores on the Clinician-Administered Dissociative States Scale (CADSS) similar to those for placebo.
The Phase 2 trial evaluated whether KET01 administered in doses of 240 mg/day and 160 mg/day for 15 days to patients with TRD as an adjunct treatment to standard antidepressants can improve depressive symptoms compared to placebo. Recruitment stopped early after including 27 patients with TRD instead of 99 due to the effects of COVID-19 and very stringent criteria for the definition of treatment-resistant depression on recruitment.
The primary endpoint, change in MADRS from baseline to day 15, showed a mean advantage of -4.99 units compared with placebo (95% confidence interval (CI): -11.81, 1.83, p=0.1499), suggesting a positive trend in efficacy for the highest tested dose (240 mg/day) on the established MADRS rating scale for depressive severity.
Additionally, the data suggest KET01 has a rapid onset of action, with a clinically meaningful improvement of -5.67 units (95%CI: -12.57, 1.23, p=0.1062) after seven days compared with placebo.
Importantly, safety results from the trial demonstrated that KET01 was well tolerated, with no treatment-related serious adverse events reported. The Clinician-Administered Dissociative States Scale (CADSS) scores were similar to those for placebo.
Dr. Hans Eriksson, HMNC Brain Health's Chief Clinical Development Officer, said, "The encouraging preliminary results we have seen demonstrate the safety of KET01, showing the potential for development of a first-in-class, oral prolonged-release formulation of ketamine treatment for patients suffering from Treatment-Resistant Depression. In addition, our data suggest that KET01 is rapidly acting with a clinically meaningful improvement compared with placebo already after 7 days, which stands in sharp contrast to standard antidepressants which have a delayed onset of action of up to several weeks."
The study was funded by the Ketabon program, which is a joint venture between HMNC Brain Health and Develco Pharma, sponsored by the University of Zurich, and conducted under the central leadership of Professor Erich Seifritz, Director of the Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich. Dr. Michael Colla coordinated the medical implementation as head of the clinical trial at the University of Zurich, as the successor of Prof. Annette Brühl after she moved to the University of Basel. The statistical evaluation of the study was carried out by SCOPE, a globally renowned CRO.
Professor Seifritz commented, "We are pleased with the top-level results from this Phase 2 study on Treatment-Resistant Depression with KET01, as they hold significant positive implications for the clinical development of oral prolonged-release ketamine to help those afflicted, making up as many as 30 percent of depression patients. Not only does the data suggest this to be a potentially safer treatment for people suffering from Major Depressive Disorder who have not found currently available antidepressants effective, but it could potentially be expanded to include additional mental-health indications in the future. Ketabon and the University of Zurich will continue to work together in the development of KET01, with future studies being planned."
HMNC Brain Health, in partnership with Develco Pharma, is about to start a multinational, larger CRO-led Phase 2 randomized, double-blind, placebo-controlled trial in patients with TRD in the second quarter of 2022. First results are expected for mid-2023.
"We are highly encouraged by the findings in this study, showing a clinically meaningful improvement and excellent tolerability in patients treated with 240 mg/day KET01. We will bring our experiences from this study to further trials with KET01 and are looking forward to the next steps in the development of this promising medication", said Develco Pharma CEO Dr. Martin Renner.
Dr. Eriksson added, "The suggested clinically relevant improvement in efficacy and the good safety and tolerability profile that we saw in the Phase 2 Proof-of-Concept trial support our plans for the larger study which we are preparing to launch. With the capabilities of our team and strong Scientific Advisory Board, we are well placed to undertake the next steps for progressing Ketabon towards more studies and the pathway to approval and commercialization."