Alzheimer's disease research
Disease-modifying drug candidates

Alzheimer's disease research

Section Title: Disease-modifying drug candidates
Table Section Text: None

Target/Approach	Notes (Theoretical)	Candidate Name	Trial Phase	Trial Start Date	Expected End Date	Planned Enrollment	AD population targeted (severity)	AD population targeted (genetic)	Comments

Currently Active

Neuroprotection	Neuroprotective Peptide, intra-nasal	AL-108	Phase II (completed)	Jan 2007	Jan 2008	120	Mild Cognitive Impairment	n/a	Deemed a Success; Phase III to start[dubious – discuss]

Brain Cell Apoptosis Inhibitor	Operates through multiple mechanisms: Blocks the action of neurotoxic beta-amyloid proteins and inhibits L-type calcium channels, modulates the action of AMPA and NMDA glutamate receptors, may exert a neuroprotective effect by blocking a novel target that involves mitochondrial pores, and blocks a number of other receptors, including α-adrenergic, 5-HT2C, 5-HT5A, and 5-HT6	latrepirdine (trade name: Dimebon)	Phase II (completed)	Sep 2006	Nov 2007 (actual)	183	Mild-to-Moderate	n/a	In March 2010, Pfizer announced that the Phase III CONNECTION trial failed to meet its primary and secondary endpoints. In January 2012, it was announced that the Phase III CONCERT study did not meet its co-primary endpoints.

Natural Antibodies to amyloid beta	human plasma source limits supply	IVIg	Phase II (completed)	Feb 2006	June 2007	24	Mild-to-Moderate	n/a	Deemed a Success; Phase III to start

Vaccine to amyloid beta	Injects modified amyloid beta (active vaccine)	ACC-001	Phase II	Nov 2007	Mar 2012	228	Mild-to-Moderate	n/a	Sequel to famous AN-1792 Vaccine Trial

Discontinued

Gamma Secretase Modulator/NSAID	Shifts amyloid beta production to shorter and less toxic species. Targets γ-secretase.	R-flurbiprofen (Flurizan, MPC-7869)	Phase III (completed)	Feb 2005	May 2008	1,600	Mild	n/a	Myriad Genetics concluded that the drug did not improve thinking ability or the ability of patients to carry out daily activities significantly more than those patients with placebo.

Gamma Secretase Inhibitor	Inhibits Gamma Secretase, which reduces amyloid beta levels	Semagacestat (LY450139)	Phase III (completed)	Sep 2008	Apr 2011	1,100	Mild-to-Moderate	n/a	On August 17, 2010, Eli Lilly announced that it would "halt development of semagacestat" as it "did not slow disease progression and was associated with worsening...cognition and the ability to perform activities of daily living." Also, it is "associated with an increased risk of skin cancer."

Antibody to amyloid beta	Mimics natural antibody triggered by AN-1792	Bapineuzumab (aab-001)	Phase III (completed)	Dec 2007	Apr 2012	1,121	Mild-to-Moderate	Apolipoprotein E4 Carriers only	On August 6, 2012, Pfizer and Johnson & Johnson said they are "ending development of an intravenous formulation" of bapineuzumab. Phase III trials "showed no treatment effect on either cognitive or functional outcomes.

Antibody to amyloid beta	Mimics natural antibody triggered by AN-1792	Bapineuzumab (aab-001)	Phase III (completed)	Dec 2007	Jun 2012	1,331	Mild-to-Moderate	Apolipoprotein E4 Non-Carriers only	On August 6, 2012, Pfizer and Johnson & Johnson said they are "ending development of an intravenous formulation" of bapineuzumab. Phase III trials "showed no treatment effect on either cognitive or functional outcomes.

Metal-Protein Interaction Attenuation	Primary targets are copper and zinc. Removes copper and zinc from cerebrospinal fluid.	PBT2 (8-hydroxy quinoline)	Phase II (completed)	Dec 2006	Dec 2007	80	Early Alzheimer's disease	n/a	"Did not meet its primary endpoint of a statistically significant reduction in the levels of beta-amyloid plaques in the brains prodromal/mild Alzheimer's disease patients." "No improvement was observed on the secondary endpoints of brain metabolic activity, cognition and function; however, there was a trend towards preserving hippocampal brain volume".

Fibrilization of amyloid beta	Breaks down neurotoxic fibrils, allowing amyloid peptides to clear the body rather than form amyloid plaques.	ELND005 (AZD-103, scyllo-Inositol)	Phase II (completed)	Dec 2007	May 2010	353	Mild-to-Moderate	n/a	Phase I produced encouraging results by August 2007. In December 2009, Elan and Transition jointly reported that the Phase II study has been modified so that only the 250 mg twice daily dose will be continued due to "greater rates of serious adverse events, including nine deaths," in the higher dose groups (1000 mg and 2000 mg dosed twice daily).

Sentence(s)

R-flurbiprofen (MPC-7869) is a gamma secretase modulator.

final_sentence: R-flurbiprofen (MPC-7869) is a gamma secretase modulator.