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At 2023 Conference on Clinical Trials in Alzheimer’s Disease (CTAD)held October 24-27 in Boston, Massachusetts, new 18-month data from the Phase 2 OVERTURE study (NCT03556280) highlights the impacts of Cognito’s gamma sensory stimulation approach in slowing of the progression of Alzheimer’s disease (AD).1
In the open-label extension, a mean total of 422.27 days to achieve at least a 15% decline in Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) total score was recorded for people using the stimulation device, compared to 150.96 days for those using sham. Additionally, continuation of treatment with the therapy showed a lower rate of brain atrophy than observed in the sham arm during the randomized controlled period and OLE. Above all, these data are based on 6-month results previously published which were presented to the 2022 American Academy of Neurology (AAN) Annual Meeting.
“We are excited to share results from our Phase 2 open-label extension study OVERTURE, which strengthens the safety, high compliance and sustained 18-month therapeutic benefits of our disease-modifying treatment for mild Alzheimer’s disease to moderate. » Brett Vaughan, CEO of Cognito Therapeutics, said in a statement.1 “Our Phase 2 study demonstrates preservation of cognition and function via approved endpoints, in conjunction with significant preservation of brain volume, a key biomarker that was consistent with improved patient outcomes.
Of the 53 patients who completed the 6-month double-blind trial, 44 (83%) chose to enter OLE where they received a daily 1-hour treatment of gamma stimulation for 12 additional months. Although half of these patients completed all study assessments; results suggest that switching to active treatment after 6 months reduces rates of brain atrophy compared to the randomized controlled period. Notably, an early-start and delayed-start model showed comparable estimated slopes for ADCS-ADL and total brain volume over 18 months.
During the double-blind and OLE periods, investigators observed no amyloid-related imaging abnormalities (ARIAs) or serious adverse events (AEs). Higher rates of headache (21.7% vs. 10.7%) and tinnitus (15.2% vs. 0.0%) were observed during the randomized portion of the trial, and the Safety results remained similar throughout the 18-month period. Furthermore, more than 80% of patients adhered to active treatment, whether started during the double-blind or OLE period. Additionally, with treatment, patients showed clinical functional stability at 18 months based on ADCS-ADL total scores.
“The DMT potential of Cognito will be instrumental in helping to attenuate accelerated brain atrophy caused by anti-amyloid monoclonal antibodies, with no ARIA shown over 18 months in phase 2 OLE data,” Marwan Sabbagh, MD, behavioral neurologist at Barrow Neurological Institute. and Chairman of the Medical Advisory Board of Cognito Therapeutics, said in a statement.1 “In addition to providing an attractive alternative to ABM, Cognito therapy can also act as a combination therapy to create a continuum of care for AD. This creates a unique value proposition for Cognito to address a broad population of AD patients, with a therapy that has a clean ARIA-free safety profile, convenient administration, and no amyloid-beta PET testing required.
In 6-month data presented at AAN 2022, patients treated with gamma sensory stimulation demonstrated a statistically significant rate of 83% (P. <.013) reduction in cognitive decline, as represented by Mini-Mental State Examination scores. The 2 treatment groups showed no statistically significant differences on other outcome measures such as Modified AD Composite Score (MADCOMS), Alzheimer's Disease Assessment Scale-14 (ADAS-Cog14) and Clinical Dementia Rating-Sum of Boxes (CDR-SB).2
Through quantitative MRI analysis, investigators identified a significant rate of 72% (P. <0.01) reduction in brain atrophy in the active treatment group compared to sham treatment. In addition, reduced lateral ventricular enlargement and decreased loss of cortical thickness in the occipital cortex were also observed, and no patients demonstrated the presence of imaging abnormalities related to the amyloid.
In a subanalysis of this trial, patients (n = 22) who received gamma sensory stimulation showed significantly reduced periods of nocturnal activity, in contrast, worsening sleep quality in those receiving stimulation over a period of time. 24-week treatment course (both P. <.03). The average nighttime period was 7.23 hours for the treated group and 7.64 hours for the sham group. The difference between the second 12-week period and the first 12-week period was only a few minutes. Specifically, the difference was –2.65 minutes for the treated group and 2.07 minutes for the sham group.3
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