Perspectives from the Alzheimers Association National Lieutenant - PowerPoint PPT Presentation

Perspectives from the Alzheimer’s Association National Lieutenant Governors Association Federal-State Relations Meeting March 24, 2016 Washington, D.C. James Hendrix, Ph.D. Director of Global Science Initiatives The Alzheimer’s Association

2 Alzheimer’s & Related Dementias

3 Alzheimer’s – Plaques & Tangles tangles plaques

Risk Related to Cognitive Decline & Alzheimer’s • Age: The greatest known risk factor • Heart-head connection • Increased risk suspected if high blood pressure, heart disease, stroke, diabetes and high cholesterol • Head injury • Genetic risk (APOE4) 4

Statement of Evidence: Modifiable Risk Factors for Cognitive Decline & Dementia (1) Regular physical activity and management of cardiovascular risk factors (diabetes, obesity, smoking, and hypertension) have been shown to reduce the risk of cognitive decline and may reduce the risk of dementia; (2) Healthy diet and lifelong learning/cognitive training may also reduce the risk of cognitive decline; (3) There are still many unanswered questions and significant uncertainty with respect to the relationship between individual risk factors and dementia. 5

6 to LOVE Ways Brain Your 10

Alzheimer’s disease 7 Continuum of Alzheimer’s Disease Adapted from Sperling et al. 2011 Normal

DVR = 1.0 2.0 L 8 PET Amyloid Imaging R Aging Disease Figures courtesy Johnson/ Reisa Normal Alzheimer ’ s of Drs Keith Sperling

9 Possible Prevention of Alzheimer’s?

Current Alzheimer’s Therapies: Symptomatic Cholinesterase Inhibitors Tacrine (Cognex) Donepezil (Aricept) Rivastigmine (Exelon) Galantamine (Razadyne) Glutamate Moderators Memantine (Namenda) Combination Therapies Donepezil & memantine (Namzaric) 1 0

Clinical Drug Development Pipeline for Alzheimer’s Disease Calcoen, Elias & Yu. Nature Reviews Drug 1 1 Discovery 14, 161–162 (2015)

Therapeutic Agents in Phase I and II Clinical Trials for Alzheimer’s Disease • AADvac1 • LY3202626 • CPC-201 • MK-7622 • ABT-957 • MEDI1814 • Crenezumab • Nicotinamide (MABT5102A) • Aducanumab(BIIB • PF-06751979 • n-PUFA 037) • DAIO-B • S-Equol • Omega-3 • Allopregnenalone • D-ribose • TPI-287 • PQ912 • BI 409306 • E2609 • Transcranial direct • PXT00864 • Crenezumab current stimulation • Exendin-4 • Rasagiline (MABT5102A) (tDCS) • Genistein • RO4602522 • CT1812 • Transcranial • Insulin • RPh201 magnetic • Curcumin • Insulin Glulisine • Sargramostim stimulation (TMS) • DBS-f (Deep brain • IVIg • Simvastatin • ANAVEX2-73 stimulation -fornix) • JNJ-54861911 • SUVN-502 • Atomoxetine • GC021109 • Ladostigil • T3D-959 • AZD0530 • Insulin • Levetiracetam • T-817MA • BAN2401 • JNJ-54861911 • Lipoic Acid • Transcranial • BI 409306 • KHK6640 • Liraglutide magnetic • Blood plasma • Lu AF20513 stimulation (TMS) • Mesenchymal • CNP520 • LY3002813 stem cells As of 12/2015 (Jan 16, 2015) 1 2

Therapeutic Agents in Phase III Clinical Trials for Alzheimer’s Pioglitazone Gantenerumab Aducanumab Takeda Hoffman-La Roche Biogen PPAR-gamma activator Monoclonal antibody against Sodium Oligo-mannurate (GV-971) Antibody to beta amyloid beta-amyloid Shanghai Greenvalley Pharmaceuticals ALZT-OP1 Inhibits beta-amyloid aggregation Part of DIAN-TU Solanezumab AZTherapeutics Insulin Eli Lilly Alzheimer’s Disease Drug combination Humanized Ab against amyloid Cooperative Study TRx0237 AZD3293 IVIg and Albumin TauRX Astrazeneca Grifols Tau aggregation inhibitor BACE inhibitor Verubecestat (MK8931) Intravenous immunoglobulin Merck LU AE58054 Azeliragon BACE inhibitor H. Lundbeck TransTech Pharma 5HT6 receptor antagonist Inhibits receptor for advanced Masitinib glycation end-products AB Science Encenicline/MT-4666 Inhibitor of c-KIT cell Forum Pharmaceuticals signaling Nilvadipine Mitsubishi/Tanabe St. James Hospital Pharmaceutical Corp. Calcium Channel Blocker Nicotinic receptor agonist As of 12/2015 1 3 (Jan 16, 2015)

Experimental Drug Trial Results: Potential Disease Modifying Treatments • Solanezumab (Lilly) – New analysis of results from two prior phase 3 studies suggests it may slow cognitive decline – On-going Phase 3 used Amyloid PET to enroll participants • Aducanumab (Biogen) – Small Phase 1b suggests may slow cognitive decline in people w/ mild Alzheimer’s – Launched two Phase 3 clinical trials using Amyloid PET to enroll participants 1 4

Experimental Drug Trial Results: Potential Symptomatic Treatments • RVT-101 (Axovant) – Suggests improvement in cognition when added to donepezil (Aricept) – Announced plans to launch Phase 3 • AVP-923: Dextromethorphan/Quinidine (Avanir) – Significant improvement in agitation – Determining next steps 1 5

1 6 alz.org