Investigative Therapy Linked to Improved Cognitive, Behavioral, Functional, and Motor Outcomes for People with Dementia with Lewy Bodies

People with dementia with Lewy bodies (DLB) treated with CT1812 (zervimesine; Cognition Therapeutics, Purchase, NY), an investigational oral therapy, showed significant improvements in cognitive, behavioral, functional, and motor symptoms according to recent results of the phase 2 SHIMMER clinical trial (NCT05225415) presented at the International Lewy Body Dementia Conference (LDBDC) in Amsterdam, Netherlands. CT1812 is an experimental sigma-2 receptor antagonist that targets amyloid beta oligomers.

SHIMMER was an exploratory, double-blind, placebo-controlled clinical trail that included 130 adult participants with mild-to-moderate DLB randomized to receive either oral CT1812 (100 mg or 300 mg) or placebo daily for 6 months. The primary endpoint was safety and tolerability based on incidence and severity of adverse events (AEs), with key secondary endpoints assessing Neuropsychiatric Inventory (NPI), Alzhiemer Disease Cooperative Study–Activities of Daily Living (ADCS-ADL), Clinician Assessment of Fluctuation (CAF), and Movement Disorder Society–United Parkinson’s Disease Rating Scale (MDS-UPDRS) scores. The following key results were reported.

Behavioral Outcomes:

• CT1812-treated participants showed an 86% improvement in NPI scores vs placebo.
• These individuals also showed fewer or less severe hallucinations and delusions and less anxiety and agitation.
• Care partners also reported lower levels of distress caused by behavioral symptoms.

Functional Outcomes:

• CT1812-treated participants preserved 52% more of their functional ability vs placebo in terms of ADCS-ADL scores.

Motor Outcomes:

• CT1812-treated participants maintained 62% more motor function compared with placebo according to the MDS-UPDRS scale.

Cognitive Outcomes:

• CT1812-treated participants demonstrated a 91% reduction in cognitive fluctuations vs placebo, per the CAF scale.

Cognitive fluctuations, a hallmark symptom of DLB, consist of sudden and unpredictable changes in attention, alertness, or mental clarity, characterized by rapid shifts between lucidity and disorientation, as well as drowsiness or decreased focus.

“Patients on zervimesine had fewer cognitive fluctuations and showed better motor control than placebo-treated patients,” said Dr. James E. Galvin, MD, MPH, Director of the Comprehensive Center for Brain Health at the University of Miami Miller School of Medicine and study director and principal investigator for SHIMMER. “These positive changes were reflected in zervimesine-treated patients’ ability to dress, feed and bathe themselves and hold conversations, which are activities of daily living reflected in the ADCS-ADL score. The reduction in these symptoms may allow people with DLB to live at home with the assistance of their care partners and be present in their loved one’s lives longer.”

CT1812 met the primary safety and tolerability endpoint, showing a favorable profile with most treatment-related AEs being mild or moderate. CT1812 also was recently evaluated as a treatment for people with Alzheimer disease (AD) in the phase 2 SHINE clinical trial (NCT03507790), where it was associated with slower cognitive decline vs placebo.