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NAME: AF 102B

OTHER NAMES: cevimeline HCL, Evoxac™

FDA PHASE: Discontinued

ROLE IN ALZHEIMER'S DISEASE: Improve neuronal responsiveness to neurotrophic factors.

NAME: Flurizan™

OTHER NAMES: MPC-7869, r-flurbiprofen, tarenflurbil

FDA PHASE: Discontinued

MECHANISMS: Selective amyloid-lowering agent (SALA). Flurizan lowers levels of Aβ42, a major constituent of plaques and a key pathogenic agent of Alzheimer disease.

ROLE IN ALZHEIMER'S DISEASE: Selectively lowers production of toxic amyloid (Aβ42) and thus inhibits the cascade of amyloid accumulation, plaque formation, and neurodegeneration that are the hallmarks of dementia. Early intervention, and targeting the initial stage of the disease process, offers the potential for a therapy with disease modification properties. In mouse models, Flurizan™ reduced insoluble amyloid in the brain and improved spatial reference learning and memory.

NAME: LY450139 Dihydrate

OTHER NAMES: hydroxylvaleryl monobenzocaprolactam, Semagacestat

FDA PHASE: Discontinued

MECHANISMS: γ-secretase inhibitor

ROLE IN ALZHEIMER'S DISEASE: Eli Lilly has halted development and further testing of Semagacestat (LY450139), announced on Aug 17 2010. Preliminary analysis of from two Phase III trials (NCT00762411 and NCT00594568) have shown that 'patients treated with semagacestat worsened to a statistically significantly greater degree than those treated with placebo' and furthermore, 'semagacestat is associated with an increased risk of skin cancer compared with those who received placebo'. See related Alzforum News Lilly Halts IDENTITY Trials as Patients Worsen on Secretase Inhibitor and Lilly press release Lilly Halts Development of Semagacestat for Alzheimer's Disease Based on Preliminary Results of Phase III Clinical Trials. γ-secretase inhibitor LY450139 completed Phase 2 clinical testing in June 2007. This was a collaborative effort of the Alzheimer’s Disease Cooperative Study (ADCS) group and sponsor company. In a multicenter, randomized, double-blind, dose-escalation, placebo-controlled trial, biomarker analysis of the treatment group showed that plasma Aβ40 decreased by 58.2 percent in the 100 mg/day group, and by 64.6 percent in the 140 mg/day group; the decrease in CSF Aβ40 was smaller and not statistically significant. See ARF related news story. Using a novel radiolabeling technique to identify newly synthesized protein in the CSF, LY450139 has been shown to decrease synthesis of Aβ without affecting clearance (see ARF related news story and Bateman et al., 2009)

NAME: NIC5-15

FDA PHASE: Phase II/IIa/IIb

MECHANISMS: NIC5-15 is a naturally occurring anti-diabetic agent with insulin-sensitizing properties. It has also been shown to act as a gamma-secretase inhibitor that spares Notch.

1 to 4 of 4 results