New data from the OVERTURE I/II study reveals that Spectris, a treatment developed by Cognito Therapeutics, significantly reduced the estimated Alzheimer’s Disease Dependence Score (DS) compared to sham treatment over 18 months. The findings, presented at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference, suggest a potential breakthrough in preserving brain structures and daily functions in patients with mild-to-moderate Alzheimer's disease (AD).
The OVERTURE I trial (NCT03556280) was a 6-month phase 2 randomized controlled trial (RCT), after which participants were invited to enroll in the 12-month open-label extension (OLE) OVERTURE II study. During the OLE, participants received 1 hour of daily active treatment with Spectris. Of the 53 participants who completed the RCT, 44 (83%) entered the OLE. Data from 39 patients (25 active, 14 sham) at 9 months and 22 patients (15 active, 7 sham) at 18 months were evaluated.
Key Findings on Alzheimer's Disease Dependence Score
The study's primary focus was the Alzheimer's Disease Dependence Score (DS), a comprehensive measure of a patient's reliance on others for daily activities. Results indicated that Spectris significantly reduced the DS compared to the sham group over the 18-month period. This suggests that Spectris may slow the progression of functional decline associated with Alzheimer's disease.
Tolerability and Safety Profile
An important aspect of the OVERTURE I/II study was the high tolerability and adherence to Spectris treatment. No serious treatment-related adverse events or amyloid-related imaging abnormalities were observed. This favorable safety profile is crucial for a treatment aimed at long-term use in an elderly population often susceptible to side effects.
Impact on Brain Structures
According to Ralph Kern, MD, MHSc, chief medical officer at Cognito Therapeutics, the study demonstrated "remarkable preservation of brain structures and daily functions, with particularly striking results in the corpus callosum." This observation is significant because the corpus callosum, which facilitates communication between the brain's hemispheres, is often affected early in Alzheimer's disease. Preserving its integrity could have a positive impact on cognitive and motor functions.
Mechanism of Action: Gamma Oscillation Stimulation
Spectris operates by stimulating gamma oscillations in the brain, which are believed to enhance the function of inhibitory neurons. This modulation may help restore neural network activity disrupted by Alzheimer's disease, potentially improving cognitive and functional outcomes.
Ongoing Phase 3 HOPE Trial
The promising results from the OVERTURE I/II study have paved the way for the ongoing phase 3 HOPE pivotal trial (NCT05637801). This trial will further investigate the efficacy and safety of Spectris in a larger patient population with mild-to-moderate Alzheimer's disease. The HOPE trial is critical to confirming the potential of Spectris as a disease-modifying treatment.
