Therapy Areas: Infectious Diseases
Cortexyme's Approach to Addressing a Key Underlying Cause of Alzheimer's Detailed at Alzheimer's Association International Conference 2019
19 July 2019 - - US-based biopharmaceutical company Cortexyme, Inc. (NASDAQ: CRTX) has presented clinical data that supports its ongoing work to pioneer a novel, disease-modifying therapeutic approach to treating a key underlying cause of Alzheimer's and other degenerative diseases, the company said.
In a poster presentation at the Alzheimer's Association International Conference 2019 (AAIC), researchers highlighted the Phase 1b clinical development experience of COR388, the company's lead investigational gingipain inhibitor, and provided an overview of the design for the GAIN trial, the company's large, international Phase 2/3 trial in patients with mild to moderate Alzheimer's disease. AAIC is the largest international meeting dedicated to advancing dementia science and is being held this week in Los Angeles.
In a Developing Topics poster (P4-663), researchers detailed the rationale for and design of the GAIN trial, which began enrolling subjects in the United States in April 2019.
The trial represents the first large, randomized late-stage clinical study evaluating the gingipain hypothesis, which is based upon growing evidence that the bacterium most commonly associated with chronic periodontal disease, Porphyromonas gingivalis, plays a key role in the development of AD, given its identification in the brains of AD patients and ability to cause neurodegeneration, inflammation, and other pathology associated with Alzheimer's in animal models.
In these models, the pathological effects were blocked by COR388, which targets the gingipains, or toxic proteases, released by P. gingivalis as it colonizes tissue.
The GAIN trial is based on Phase 1b data demonstrating benefits on both biomarkers and cognitive endpoints. After a 10-day multiple ascending dose study in 24 older healthy volunteers showed an encouraging tolerability and safety profile, a 28-day study of nine subjects with mild to moderate AD between the ages of 55 and 85 was conducted.
Participants showed a trend to improvement on several measures of cognition, including the Mini-Mental State Exam and Cambridge Neuropsychological Test Automated Battery (CANTAB) memory composite of cognitive function score, measures commonly used to assess cognitive impairment in Alzheimer's patients.
Researchers also reported a statistically significant improvement for COR388 versus placebo on multiple measures of the Winterlight Cognitive Assessment, a new speech-based testing platform intended to identify cognitive impairment associated with dementia.
Across the Phase 1b study, as well as single and multiple ascending dose studies in healthy volunteers, COR388 twice daily was found to be well tolerated and brain penetrant.
As part of an AAIC news briefing earlier this morning, lead author Michael Detke, M.D., Ph.D. shared data from the patient cohort demonstrating a reduction in markers of inflammation in the blood (plasma RANTES), as well as a reduction in pathological ApoE fragments in the cerebrospinal fluid, which suggests another potential benefit of inhibiting gingipain activity in the brains of patients.
Spurred by the totality of data from Phase 1a/b testing, investigators are now enrolling subjects in the GAIN trial, which is targeting an enrollment of up to 570 patients with mild to moderate AD at ~90 sites in the United States and Europe. Participants are randomized to one of two doses of COR388 capsules (40mg or 80mg twice daily) or placebo.
The primary endpoint of the study is the mean change in the Alzheimer's disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11), a measure that has supported past regulatory approval of drugs to treat Alzheimer's disease, along with secondary endpoints of function ADCS-ADL and CDR-SB.
Cortexyme has developed a sensitive assay for Porphyromonas gingivalis DNA in the central nervous system, and biomarkers of the infection in the saliva, blood and CSF are being closely tracked for responder analyses. Top-line results from the GAIN trial are expected by the end of 2021.
Cortexyme (NASDAQ: CRTX) is a clinical stage biopharmaceutical company pioneering a novel disease-modifying therapeutic approach to treat a key underlying cause of Alzheimer's disease and other degenerative diseases. Cortexyme is targeting a specific, infectious pathogen found in the brain of Alzheimer's patients and tied to neurodegeneration and neuroinflammation in animal models.
The company's lead investigational medicine, COR388, is the subject of the GAIN trial, an ongoing Phase 2/3 clinical study in patients with mild to moderate Alzheimer's disease.
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