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Perspectives from the Alzheimer's Association

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Perspectives from the Alzheimer's Association 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 Alzheimer’s & Related Dementias 2 Alzheimer’s – Plaques & Tangles tangles plaques 3 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 10 Ways to LOVE Your Brain 6 Continuum of Alzheimer’s Disease Normal Alzheimer’s disease Adapted from Sperling et al. 2011 7 PET Amyloid Imaging Aging Normal s ’ DVR = 1.0 2.0 Disease Alzheimer Figures courtesy of Drs Keith 8 Johnson/ Reisa R L Sperling Possible Prevention of Alzheimer’s? 9 Current Alzheimer’s Therapies: Symptomatic Cholinesterase Inhibitors Tacrine (Cognex) Donepezil (Aricept) Rivastigmine (Exelon) Galantamine (Razadyne) Glutamate Moderators Memantine (Namenda) Combination Therapies Donepezil & memantine (Namzaric) 10 Clinical Drug Development Pipeline for Alzheimer’s Disease Calcoen, Elias & Yu. Nature Reviews Drug Discovery 14, 161–162 (2015) 11 Therapeutic Agents in Phase I and II Clinical Trials for Alzheimer’s Disease • AADvac1 • LY3202626 • CPC-201 • MK-7622 • ABT-957 • MEDI1814 • Crenezumab • Nicotinamide • Aducanumab(BIIB • PF-06751979 (MABT5102A) •n-PUFA 037) • S-Equol •DAIO-B • Omega-3 • Allopregnenalone • TPI-287 • D-ribose • PQ912 • BI 409306 • Transcranial direct • E2609 • PXT00864 • Crenezumab current stimulation • Exendin-4 • Rasagiline (MABT5102A) (tDCS) • Genistein • RO4602522 • CT1812 • Transcranial • Insulin •RPh201 •Curcumin magnetic • Insulin Glulisine stimulation (TMS) • Sargramostim • DBS-f (Deep brain •IVIg • ANAVEX2-73 • Simvastatin stimulation -fornix) • JNJ-54861911 • Atomoxetine • SUVN-502 • GC021109 • Ladostigil • AZD0530 • T3D-959 • Insulin • Levetiracetam • BAN2401 • T-817MA • JNJ-54861911 • Lipoic Acid • BI 409306 • Transcranial • KHK6640 • Liraglutide magnetic • Blood plasma • Lu AF20513 • Mesenchymal stimulation (TMS) • LY3002813 • CNP520 stem cells As of 12/2015 (Jan 16,12 2015) Therapeutic Agents in Phase III Clinical Trials for Alzheimer’s Pioglitazone Gantenerumab Aducanumab Takeda Biogen Hoffman-La Roche PPAR-gamma activator Monoclonal antibody against Sodium Oligo-mannurate (GV-971) Antibody to beta amyloid beta-amyloid Shanghai Greenvalley Pharmaceuticals ALZT-OP1 Part of DIAN-TU Inhibits beta-amyloid aggregation AZTherapeutics Insulin Solanezumab Eli Lilly Alzheimer’s Disease Drug combination Humanized Ab against amyloid AZD3293 Cooperative Study TRx0237 IVIg and Albumin TauRX Astrazeneca Grifols Tau aggregation inhibitor BACE inhibitor Intravenous immunoglobulin Verubecestat (MK8931) Merck Azeliragon LU AE58054 BACE inhibitor TransTech Pharma H. Lundbeck 5HT6 receptor antagonist Inhibits receptor for advanced Masitinib glycation end-products AB Science Encenicline/MT-4666 Inhibitor of c-KIT cell Forum Pharmaceuticals signaling Mitsubishi/Tanabe Nilvadipine Pharmaceutical Corp. St. James Hospital Nicotinic receptor agonist Calcium Channel Blocker As of 12/2015 13 (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 14 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 15 alz.org 16.
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