Sinaptica Therapeutics Announces Publication of Positive Results from Phase II Trial Evaluating the Potential of Precision-Delivered Noninvasive Neurostimulation Treatment for Mild-to-Moderate Alzheimer’s Disease
Phase II sham-controlled randomized trial met its primary endpoint with statistical significance; treatment slowed cognitive decline by 82% over 6 months in the treated population compared to sham with no safety issues
Key secondary measures of cognitive function also reached statistical significance, including a 108% difference in function as measured by ADCS-ADL
Trial results published in the peer-reviewed neurology journal Brain
Company was formed to develop SinaptiStim™ – AD System based on the hypothesis tested in the Phase II trial and plans to evaluate its investigational device in a pivotal trial beginning in 2023
CAMBRIDGE, Mass., October 25, 2022 – Sinaptica Therapeutics, Inc., a clinical-stage company leading the development of a new class of personalized electromagnetic therapeutics to treat neurodegenerative diseases, today announced the publication of a Phase II trial conducted independently under the leadership of its co-founders, which yielded positive results demonstrating that precision-delivered noninvasive brain stimulation has the potential to slow the progression of cognitive and functional decline in patients with mild-to-moderate dementia due to Alzheimer’s disease. The findings have been published in the peer-reviewed neurology journal Brain.
Fifty patients were enrolled in the Phase II randomized, double-blind, sham-controlled trial. The patients underwent a novel diagnostic assessment using both transcranial magnetic stimulation (TMS) and electroencephalogram (EEG) to personalize key treatment parameters to each patient. The trial included a 24-week treatment period, with an initial 2-week intensive course during which repetitive transcranial magnetic stimulation (rTMS) or sham was applied over the precuneus daily (five times per week), followed by a 22-week maintenance phase during which the same stimulation was applied weekly. rTMS was given as an add-on to standard treatment with acetylcholinesterase inhibitors.
The primary outcome measure was the change at 24 weeks from baseline of the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB) score (scores range from 0 to 18, with higher scores indicating worse cognition and daily function). Over the course of the trial, patients in the treatment group showed a stable performance while patients in the sham (placebo) group showed a general worsening of cognitive performance. Specifically, the precision-delivered rTMS treatment slowed cognitive decline, compared to the sham intervention, by 82% at 6 months, representing a treatment difference in the CDR-SB score of 1.3 points (p=0.009). Treatment was well tolerated, and no serious adverse events were observed in patients treated with rTMS for 6 months.
“We are very encouraged by the statistically significant and clinically meaningful results of our precision-delivered noninvasive neurostimulation approach in patients with mild-to-moderate Alzheimer’s disease,” said lead investigator Giacomo Koch, MD, PhD, co-founder of Sinaptica Therapeutics, Full Professor of Physiology at University of Ferrara, Italy and Director, Non-invasive Brain Stimulation Laboratory, at Santa Lucia Foundation, IRCCS in Rome, Italy, which is where the Phase II trial was conducted. “The results are particularly notable because they were achieved in patients already showing symptoms of mild-to-moderate dementia, in which cognitive decline progresses more rapidly and is less responsive to drug interventions. As one of the largest trials of brain stimulation ever conducted in Alzheimer’s disease resulting in a therapeutic benefit and the first to use a precision-delivered protocol targeting the precuneus, we have validated the potential of our novel approach to be a new therapeutic tool in the treatment of Alzheimer’s disease and potentially other neurodegenerative diseases.”
Patients in the treatment group also showed better performance compared to the sham group in three key secondary outcome measures, which reached statistical significance. In the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scale, treatment showed an improvement in cognitive function compared to sham with an estimated mean change in ADCS-ADL scores of -0.7 for the treatment group and 7.5 for the sham group, demonstrating a 108% difference between the treatment and sham groups at 6 months. The Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE) also demonstrated a slowing of functional decline, with an estimated mean change in ADAS-Cog score of -0.67 for the treatment group and -4.2 for the sham group and an estimated mean change in MMSE score of 0.30 for the treatment group and 1.8 for the sham group.
In addition, neurophysiological results showed that precuneus cortical excitability remained unchanged after 6 months in the treatment group, whereas it was significantly reduced in the sham group as a reflection of pathological decline of brain activity, suggesting a neuroprotective treatment effect.
“Alzheimer’s disease patients develop alterations to the Default Mode Network, or DMN, a key network responsible for episodic memory for which the precuneus is a key region,” said study investigator Emiliano Santarnecchi, PhD, co-founder of Sinaptica Therapeutics, Associate Professor of Radiology at Harvard Medical School, as well as Director, Precision Neuroscience & Neuromodulation Program and Director, Network Control Laboratory, at Massachusetts General Hospital in Boston, MA. “In this Phase II trial, we have shown that the DMN can be targeted by precision-delivered noninvasive therapeutic interventions that utilize electromagnetic brain stimulation to improve plasticity and stabilize network connectivity. We believe this is an important development with the potential to address the staggering unmet need in the treatment of Alzheimer’s disease and warrants further evaluation.”
Dr. Koch and Dr. Santarnecchi founded Sinaptica Therapeutics to further develop, test, and translate the groundbreaking science into real-world therapeutic solutions, including the development of an investigational precision-delivered noninvasive neurostimulation device for treating mild-to-moderate Alzheimer’s disease.
“Sinaptica Therapeutics is pioneering a new class of electromagnetic therapeutics that integrate AI-derived protocols, brain modeling and network targeting to achieve a personalized and precision-delivered approach to slowing the progression of cognitive and functional decline in Alzheimer’s disease,” said Rich Macary, President of Sinaptica Therapeutics. “These unprecedented peer-reviewed clinical results demonstrate the potential for this new class of personalized electromagnetic therapeutics to treat cognitive and functional decline safely and noninvasively in Alzheimer’s disease patients. We look forward to confirming the significant Phase II results and obtaining additional clinical data in a larger, multi-center, pivotal trial using our patent-pending investigational SinaptiStim™ – AD System, which has been granted Breakthrough Device Designation by the U.S. Food and Drug Administration.”
About Sinaptica Therapeutics
Sinaptica Therapeutics is a clinical-stage electromagnetic therapeutics company pioneering a personalized noninvasive brain stimulation approach with the potential to revolutionize the treatment of Alzheimer’s disease (AD). The company’s personalized, noninvasive brain stimulation platform is underpinned by significant clinical trial results showing an unprecedented reduction in cognitive decline and improved function in mild-to-moderate Alzheimer’s disease patients. The investigational SinaptiStim™ – AD System integrates electromagnetic stimulation of the brain with powerful proprietary artificial intelligence-derived protocols, brain modeling, and network targeting to create a personalized and precision-delivered therapeutic approach. The company plans to advance this promising science with a pivotal, randomized, controlled clinical trial. It seeks to create a new, more efficient treatment paradigm for the staggering unmet need and burden of AD, as well as other neurodegenerative disorders. The company has received Breakthrough Device Designation from the U.S. Food and Drug Administration for the patent-pending SinaptiStim™ – AD System.
The SinaptiStim™ – AD System is for investigational use only. It has not been approved by the U.S. Food and Drug Administration and is not available for commercial sale.
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