Pipeline Of Alzheimer's Drugs Targeting Amyloid-Beta Protein

Amyloid-beta protein plaques associated with Alzheimer's disease are a popular target for drugs attempting to treat the symptoms of the disease by removing the plaques or to diagnose it by detecting their presence. Many such drugs are in the pipeline, despite the failure of several of them in late-stage development (Also see "Roche Is Sudden Pioneer In Alzheimer's Research With New Trial In Early Patients" - Pink Sheet, 12 May, 2011.). Below is a list of products in clinical development.
Sponsor and Drug	Development Stage	Details
Lilly's Amyvid (florbetapir F18)	Received an FDA "complete response" letter in March	Molecular imaging agent designed to detect amyloid-beta in the brain on a PET scan (Also see "Amyvid Training Issues Lead To Complete Response Letter, Could Force More Trials" - Pink Sheet, 18 Mar, 2011.).
Lilly's solanezumab (LY2062430)	Phase III	Monoclonal antibody targeting amyloid-beta for the treatment of Alzheimer's disease. Two Phase III trials, EXPEDITION and EXPEDITION-2, have completed enrollment and are expected to finish in the first half of 2012. Interim analysis including futility analysis by a data monitoring committee will take place at the end of the year (Also see "No Big Surprises From Lilly: Management Sticks To Its Guns On Strategy" - Pink Sheet, 30 Jun, 2011.).
Johnson & Johnson/Pfizer/Elan's bapineuzumab	Phase III	Monoclonal antibody targeting amyloid plaques (Also see "J&J And Elan Strike A Deal On Key Alzheimer's Disease Assets" - Pink Sheet, 6 Jul, 2009.).
Bayer's Florbetaben (BAY94-9172)	Phase III	Binds to amyloid-beta plaques, enabling detection with PET scans (Also see "Buoyed By Strong Results, Bayer Stresses Asia Pacific As Driver Of Growth" - Pink Sheet, 29 Mar, 2011.).
Baxter's Gammagard (intravenous immune globulin). Weill Medical College of Cornell U. sponsored the study.	Phase II completed	Trial in mild to moderate Alzheimer's disease (Also see "Baxter GMP Trouble: Filter Changes In Gammagard Production Draw FDA Warning Letter" - Pink Sheet, 11 Feb, 2010.). Another formulation is FDA-approved for treatment of primary humoral immunodeficiency.
Octapharma's Octagam 10% (intravenous immune globulin)	Phase II completed	Trial in mild to moderate Alzheimer's disease had a primary endpoint of change in amyloid-beta peptide concentration of the blood plasma. A 5% formulation is FDA-approved for treatment of primary humoral immunodeficiency.
AC Immune/Genentech's MAB-5102A	Phase II (fast-track status)	Preclinical studies demonstrated that antibody induced the proposed transition from an insoluble to the soluble form of the plaque-forming beta-amyloid protein leading to memory improvement.
Johnson & Johnson/Pfizer's ACC-001	Phase II	Amyloid imaging and safety study in subjects with mild to moderate Alzheimer's disease.
Pfizer's ponezumab (PF-04360365)	Phase II	Brain and cerebrospinal fluid concentrations of amyloid-beta are among the primary endpoints.
Columbia U. study of the diabetes drug metformin	Phase II	Peripheral hyperinsulinemia can impair the clearance of amyloid-beta in the brain, so the study is testing whether lowering peripheral insulin in overweight persons with amnestic mild cognitive impairment, a transitional state between normal cognition and Alzheimer's, can decrease the risk of cognitive decline and progression to Alzheimer's.
Roche's gantenerumab and accompanying diagnostic	Phase II	Study is being conducted in 360 patients with prodromal Alzheimer's disease, aged 50 to 80, with noticeable cognitive impairments. Data are not expected until 2015 unless an interim analysis is conducted.
Bristol-Myers Squibb's BMS-708163	Phase II	Small molecule gamma-secretase inhibitor targeting amyloid-beta. Primary endpoint is safety and tolerability; secondary endpoints are the value of CSF biomarkers on progression to dementia. Interim analysis expected in the fourth quarter.
Novartis' CAD106	Phase II	Article published June 22 in the Journal of Neuroscience "conclude[s] that CAD106 immunization is suited to interfere with amyloid-beta aggregation and its downstream detrimental effects."
Prana Biotechnology's PBT-2	Australian Phase II trial planned for second half of 2011	Primary endpoint will be positron emission tomography amyloid neuroimaging and other biomarkers.
Pfizer's PF-04995274	Phase I completed	Targets cerebrospinal fluid levels of soluble amyloid-beta precursor protein fragments and amyloid-beta fragments.
United Biomedical's UB 311 vaccine	Phase I and follow-up observational study completed	Vaccine targets the N-terminal amino acids (1-14) of the amyloid beta peptide.
RaQualia Pharma's RQ-00000009	Phase I	Drug exhibited pro-cognitive activity and restored scopolamine-impaired spontaneous alteration in a rat model. Drug decreased brain cortex beta amyloid in a dose-dependent manner.
Anavex Life Sciences' Anavex 2-73	Phase I	In animal models, the drug protected against amyloid peptide-induced learning deficits, hippocampal lipid peroxidation and cell loss in the CA1 pyramidal layer and showed neuroprotective activity.
CoMentis/Astellas' CTS-21166	Phase I	A single dose produced a greater than 60% reduction of plasma amyloid beta measured either by area-under-curve over 24 hours or as a maximal reduction relative to predose levels.
QR Pharma's Posiphen	Phase I	Reduces the rate of synthesis of amyloid precursor protein in cell cultures, normal, transgenic and trisomic mice.
Noscira's NP-61	Phase I	Preclinical studies showed that NP-61 reversed cognitive deficit and halted the formation of amyloid plaques.
Lilly's LY-2886721	Phase I	In a completed Phase I study, the primary endpoints included plasma amyloid beta 1-40 concentration and CSF amyloid beta 1-40 concentration.
Eisai's E-2212	Phase I	Preclinical studies showed that E-2212 inhibited amyloid beta-42 production.
Sources: Inteleos database, ClinicalTrials.gov