Cortexyme’s Shares Implode after Alzheimer’s Disease Drug Flunks Trial

Alzheimer’s disease is a global public health threat, affecting more than 30 million people worldwide and 5.7 million in the US. A recent study found that over 90% of patients with Alzheimer’s disease showed the presence of the bacterium Porphyromonas gingivalis (P. gingivalis) and its toxins in their central nervous system. In mice experiments, the bacteria were found to travel from the mouth to the brain and spike the production of brain plaques, inflammation, and damage to neurons associated with Alzheimer’s disease.

On October 26th, Cortexyme presented topline-results from its Phase 2/3 GAIN trial, evaluating the effectiveness of atuzaginstat (COR388) to procrastinate the prevalence of P. gingivalis and potentially stifle the development of Alzheimer’s disease.

Cortexyme is a clinical-stage biopharmaceutical company pioneering therapeutics approaches designed to counteract Alzheimer’s and other neurodegenerative diseases. However, Cortexyme shares traded lower after the company’s Phase 2/3 GAIN trial did not meet its co-primary endpoints, plummeting by 76.58% on October 28th.

Even so, the downturn does not dampen Cortexyme’s active engagement with regulators, the medical community, patient advocacy groups, and other key stakeholders to further fortify the development of atuzaginstat and the second-generation lysine-gingipain inhibitor COR588, which is derived from novel compound properties and once-daily administration.

“Today marks a major milestone toward a comprehensive understanding of Alzheimer’s and slowing of disease progression. The evidence from the GAIN Trial advances our ability to identify the right patients, impact an upstream target, and improve patient outcomes,” said Casey Lynch, Cortexyme’s CEO, Co-Founder, and chair. “We are focused on next steps to advance this breakthrough treatment for the benefit of patients and their families.”

GAIN Trial

The Phase 2/3 GAIN trial is a double-blind, placebo-controlled study evaluating the efficacy of atuzaginstat, an investigational orally administered small-molecule that targets gingipain proteases from P. gingivalis.

The study enrolled 643 patients with mild to moderate signs and symptoms of Alzheimer’s disease did not demonstrate statistical significance in its co-primary cognitive and functional endpoints as measured by the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) 11 and Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS–ADL) scale.

The prespecified subgroup of patients with P. gingivalis DNA detectable in saliva at baseline presented a dose-response with a 57% slowing of cognitive decline as measured by ADAS-COg11 in the 80 mg arm and a 42% slowing in the 40 mg arm when compared to placebo.

The cognitive benefit of atuzaginstat in patients with high P. gingivalis infection was reinforced by similar results in multiple prespecified infection-related subgroups and with multiple methods of analysis. Additionally, reductions in P. gingivalis in saliva at week 24 were significantly correlated with improved outcomes at the end of the treatment period as measured by ADAS-Cog11, Clinical Dementia Rating–Sum of Boxes (CDR), Mini-Mental State Exam (MMSE), and a beneficial trend on ADCS-ADL.

“The first large clinical study of a gingipain inhibitor confirmed the benefits of treatment in the appropriate population at doses that reduce P. gingivalis. Disease modification and preservation of cognition as demonstrated in the GAIN Trial provides the foundation for altering the course of Alzheimer’s,” said Michael Detke, MD, Ph.D., Cortexyme’s CMO.

“The P. gingivalis-infected participant population was easily identified with saliva or simple blood tests and was highly responsive to atuzaginstat treatment on multiple clinical measures, and we will be discussing next steps with global regulators promptly. We are grateful to the participants, caregivers, and investigators for their participation and dedication to this important study.”

Author

Judy Ya-Hsuan Lin

Success is the ability to go from one failure to another with no loss of enthusiasm.