Over the 18-month treatment period, investigators observed no amyloid-related imaging abnormalities along with continued slowing of disease progression in patients with mild to moderate Alzheimer disease.
At the 2023 Clinical Trials on Alzheimer’s Disease (CTAD) conference, held October 24-27, in Boston, Massachusetts, new 18-month data from the phase 2 OVERTURE study (NCT03556280) highlight the impacts of Cognito’s gamma sensory stimulation approach in slowing Alzheimer disease (AD) progression.1
In the open-label extension, a mean total of 422.27 days to reach at least a 15% decline in Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) total score was recorded for those on the stimulation device vs 150.96 days for those on sham. In addition, continued treatment with the therapy showed a lower rate of brain atrophy than that observed in the sham arm during the randomized controlled period and OLE. Above all, these data build on previously released 6-month findings that were presented at the 2022 American Academy of Neurology (AAN) annual meeting.
"We are thrilled to share results from our Phase 2 OVERTURE open-label extension study, which reinforces the safety, high adherence, and long-lasting treatment benefits over 18 months of our Disease Modifying Therapy for mild-to-moderate Alzheimer disease," Brett Vaughan, chief executive officer, Cognito Therapeutics, said in a statement.1 "Our Phase 2 study demonstrates preservation of cognition and function via approvable endpoints, in conjunction with significant preservation of brain volume, a key biomarker that was concordant with improved patient outcomes."
Of the 53 patients who completed the double-blinded, 6-month trial, 44 (83%) opted to enter the OLE where they received 1-hour daily treatment of gamma stimulation for an additional 12 months. Although half of these patients completed all study assessments; results suggested that switching to active treatment after 6 months reduced rates of brain atrophy as compared with the randomized controlled period. Notably, an early-start and delayed-start model showed comparable estimated ADCS-ADL and whole brain volume 18-month slopes.
Across the double-blind and OLE periods, investigators observed no amyloid-related imaging abnormalities (ARIA) or serious adverse events (AEs). Higher rates of headache (21.7% vs 10.7%) and tinnitus (15.2% vs 0.0%) were found during the randomized portion of the trial, and safety outcomes remained similar through the 18-month period. Additionally, more than 80% of patients adhered to the active treatment regardless of starting during the double-blind or OLE period. Furthermore, through treatment, patients showed clinical stability of function at 18 months based on total ADCS-ADL scores.
"Cognito’s potential DMT will be instrumental to help mitigate the accelerated brain atrophy caused by anti-amyloid monoclonal antibodies, with no ARIA shown over 18-months in the Phase 2 OLE data,” Marwan Sabbagh, MD, a behavioral neurologist at Barrow Neurological Institute and chair of the Medical Advisory Board for Cognito Therapeutics, said in a statement.1 "In addition to providing an attractive alternative to MABs, Cognito’s therapy may 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 patient population in AD, with a therapy that has a clean safety profile with no ARIA, convenient administration and no amyloid-beta PET testing required."
In the 6-month data presented at AAN 2022, patients treated with the gamma sensory stimulation demonstrated a statistically significant 83% (P <.013) reduction in cognitive decline, represented by scores on the Mini-Mental State Examination. 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
Using quantitative MRI analysis, investigators identified a significant 72% (P <.01) reduction in brain atrophy in the active treatment group compared with sham. Furthermore, reduced lateral ventricle enlargement and diminished loss in cortical thickness in the occipital cortex was also observed, and no patients demonstrated any presence of amyloid-related imaging abnormalities.
In subanalysis of this trial, patients (n = 22) who received gamma sensory stimulation showed significantly reduced nighttime active periods, in contrast, to deterioration in sleep quality in those on sham over a 24-week treatment period (both P <.03). The average night-time period was 7.23 hours for the treatment group and 7.64 hours for the sham group. The difference between the second 12-week period and the first 12-week period was in the order only of a couple of minutes. Specifically, the difference was –2.65 minutes for the treatment group and 2.07 minutes for the sham group.3