Cognition Therapeutics (NASDAQ:CGTX) saw its shares move higher after receiving written feedback from the U.S. Food and Drug Administration on plans for a pivotal study of its investigational therapeutic zervimesine, also known as CT1812, in patients with psychosis linked to dementia with Lewy bodies.
The FDA confirmed that psychosis associated with dementia with Lewy bodies could serve as an approvable outcome and reached alignment with Cognition on key components of a pivotal trial intended to underpin a New Drug Application. Cognition expects the registrational program to commence in mid-2027.
The proposed Phase 3 protocol will enroll individuals diagnosed with dementia with Lewy bodies who experience psychotic symptoms such as hallucinations and delusions. Eligibility will include patients maintained on stable background treatments, including off-label antipsychotic medications. After screening, participants will be randomized to receive either 100 mg of oral zervimesine once daily or placebo for a treatment period of nine months.
As part of the development plan, Cognition will collaborate with the FDA on the analytical and statistical specifications required to use the neuropsychiatric inventory (NPI) as a novel primary endpoint for a pivotal study in dementia with Lewy bodies psychosis. The agency's agreement in principle to consider psychosis as an approvable outcome frames the NPI discussion as central to the registrational strategy.
The Phase 3 design builds directly on results from Cognition's Phase 2 COG1201 'SHIMMER' trial in mild-to-moderate dementia with Lewy bodies. That earlier study reported improvements in psychosis symptoms with zervimesine relative to placebo as measured by the NPI. In a recent analysis of SHIMMER data cited by the company, zervimesine slowed the progression of hallucinations and delusions by 89%.
Cognition plans to present additional analyses from the Phase 2 study in July at the Alzheimer’s Association’s International Conference, focusing on zervimesine’s effects on the hallucination and delusion components of the neuropsychiatric inventory.
Summary
The FDA's written feedback endorses psychosis as a potential approvable outcome in dementia with Lewy bodies and aligns with Cognition on pivotal trial structure, supporting a Phase 3 registrational program expected to start in mid-2027. The Phase 3 will randomize patients to 100 mg daily zervimesine or placebo for nine months and will use the neuropsychiatric inventory as a novel primary endpoint pending analytical and statistical agreements with the FDA.
Key points
- FDA concurrence that psychosis in dementia with Lewy bodies could justify approval and alignment on key trial elements - impacts biotech and pharmaceutical clinical development.
- Phase 3 registrational program anticipated to begin mid-2027, randomizing patients to 100 mg zervimesine daily or placebo for nine months - relevant to clinical trials and healthcare sectors.
- Phase 2 SHIMMER trial showed NPI-measured improvements and an analysis indicating an 89% slowing in progression of hallucinations and delusions with zervimesine versus placebo.
Risks and uncertainties
- The Phase 3 program has not yet started and is projected to begin in mid-2027, creating timing uncertainty for development milestones - affects investors and biotech market expectations.
- Use of the neuropsychiatric inventory as a novel primary endpoint requires additional analytical and statistical agreement with the FDA, introducing procedural and regulatory uncertainty in trial design - impacts regulatory and clinical development pathways.
- Eligibility allowing patients on stable off-label antipsychotic medications may affect trial population heterogeneity and outcome interpretation - relevant to trial conduct and clinical assessment.