Cognition Aligns with FDA on Phase 3 Pathway for Zervimesine in Dementia with Lewy Bodies Psychosis

Cognition Therapeutics has reached agreement with the U.S. Food and Drug Administration (FDA) on key aspects of a planned Phase 3 program evaluating zervimesine (CT1812) for psychosis associated with dementia with Lewy bodies (DLB). The agency agreed that psychosis associated with DLB could serve as an approvable outcome and aligned with the company on key elements of a registrational study intended to support a future New Drug Application (NDA).

The pivotal trial, expected to launch in mid-2027, could position zervimesine as the first FDA-approved therapy specifically targeting psychosis in DLB, an area with no current treatment options.

Disease and Mechanism

DLB is a progressive neurodegenerative disorder marked by cognitive decline, movement abnormalities, hallucinations, and delusions. Psychosis affects up to 80% of patients and is among the most distressing symptoms for patients and caregivers. Current management relies largely on off-label antipsychotics, which can cause severe and potentially life-threatening adverse reactions in some patients with DLB.

Zervimesine, an investigational oral therapy administered once daily, targets toxic protein oligomers implicated in neuronal dysfunction and disease progression. The drug is also under evaluation in Alzheimer’s disease.

Phase 3 Design and Endpoint Strategy

The planned study will enroll patients with DLB experiencing hallucinations and delusions, including those on stable background antipsychotic therapy. Participants will be randomized to receive zervimesine 100 mg orally once daily or placebo for nine months.

Cognition and the FDA are continuing discussions on analytical and statistical approaches supporting the use of the Neuropsychiatric Inventory (NPI) as a novel primary endpoint for the pivotal study.

Phase 2 SHIMMER Results

Advancement into Phase 3 builds on findings from the Phase 2 SHIMMER study (NCT05225415). According to a recent company analysis, zervimesine slowed progression of hallucinations and delusions by 89% compared with placebo, as measured by the NPI.

The therapy has also demonstrated favorable tolerability across clinical studies conducted to date.

Chief Medical Officer Anthony Caggiano, MD, PhD, said the FDA feedback provides important regulatory support for DLB psychosis as a potentially approvable treatment target. He noted that few therapies have been studied in DLB and no approved medicines currently address the condition.

President and CEO Lisa Ricciardi emphasized the need for durable therapies that not only control psychotic symptoms but also slow their progression, potentially reducing caregiver burden.

Regulatory Path Forward

Cognition plans to present additional analyses from the Phase 2 SHIMMER study at the Alzheimer’s Association International Conference (AAIC), highlighting zervimesine’s effects on hallucination and delusion components of the NPI.

Zervimesine also continues evaluation in the Phase 2 START study (NCT05531656) in patients with mild cognitive impairment and early Alzheimer’s disease. With FDA alignment secured, the company is preparing to advance into late-stage development, marking an important step toward establishing the first approved therapy specifically developed for DLB psychosis.

Reference

Cognition Therapeutics Aligns on Key Aspects of Pivotal Study for Zervimesine (CT1812) in DLB Psychosis Following Receipt of FDA Meeting Minutes | Cognition Therapeutics, Inc.