Cognition Therapeutics has announced additional data from its Phase II SHINE trial, revealing that CT1812, the company's lead candidate, significantly slowed cognitive decline in a pre-specified subgroup of mild-to-moderate Alzheimer's disease patients with lower baseline plasma p-tau217 levels. The findings, presented at the 17th Annual Clinical Trials on Alzheimer's Disease (CTAD) conference, suggest a potential targeted approach for CT1812 in earlier stages of the disease.
Cognitive Improvement in Low p-tau217 Subgroup
The analysis focused on 45 patients with baseline plasma p-tau217 levels below the median. Results showed a 95% slowing of cognitive decline in patients treated with either 100 mg or 300 mg dosages of CT1812, as measured by the 11-task Alzheimer's Disease Assessment Scale (ADAS-Cog 11). Notably, when assessed using the Mini-Mental State Examination (MMSE), the slowing accelerated to 108%, indicating that patients performed better at the end of the study than at baseline. In contrast, the 24 patients randomized to placebo exhibited cognitive decline.
According to Anthony Caggiano, MD, PhD, Cognition’s chief medical officer and head of R&D, patients treated with CT1812 essentially maintained their cognitive scores over the six-month study period. He also noted the continued separation between the active and placebo groups, suggesting a potentially greater effect with longer studies.
Implications for Future Trials
Based on these results, Cognition is planning an end-of-Phase II meeting with FDA officials in 2025 to discuss the future development of CT1812. The company is considering whether to focus future trials exclusively on patients with low p-tau217 levels or to include a broader patient population while stratifying analyses based on p-tau217 levels. This approach mirrors the strategies employed in the development of recently approved Alzheimer's drugs like Eli Lilly's Kisunla (donanemab-azbt) and Eisai/Biogen's Leqembi (lecanumab-irmb), which have also demonstrated greater efficacy in patients with lower tau levels.
Comparison with Existing Therapies
Kisunla, approved by the FDA in July, demonstrated a 35% slowing of disease progression in patients with low to medium levels of p-tau217 in the Phase III TRAILBLAZER-ALZ 2 trial. Similarly, Eisai's Clarity AD trial showed that Leqembi led to improvement or no decline in 59% of patients with low to no tau accumulation in the brain.
CT1812 Mechanism of Action
CT1812 is a sigma-2 receptor modulator designed to displace and prevent the binding of toxic oligomers of alpha-synuclein and amyloid beta. The drug is also being studied in Phase II trials for dementia with Lewy bodies (SHIMMER trial) and geographic atrophy caused by dry AMD (MAGNIFY trial).
Financial Considerations
Cognition faces the challenge of securing funding for Phase III trials. As of June 30, the company reported $28.533 million in cash and cash equivalents, which, combined with non-dilutive grants, is expected to fund operations only into the second quarter of 2025. The company is exploring potential partnerships with larger biopharmaceutical companies to address this financial need.
Lisa Ricciardi, Cognition’s president and CEO, emphasized the significant unmet need in the Alzheimer's market and the potential for partnerships to support the development of CT1812.
Alzheimer's Disease Burden
An estimated 6.9 million Americans aged 65 and older live with Alzheimer’s disease. According to a 2021 study, 50.4% of people with Alzheimer’s have mild disease, 30.3% have moderate disease, and 19.3% have severe disease.
