The Dementia Challenge: Where We Are and Where We Are Heading Yves Joanette, PhD FCAHS Scientific Director, CIHR Institute of Aging

Transcription

1 The Dementia Challenge: Where We Are and Where We Are Heading Yves Joanette, PhD FCAHS Scientific Director, CIHR Institute of Aging Disclosure Yves Joanette has no relationship with any existing or potential commercial interest linked to the data /information presented in this conference Yves Joanette is the Scientific Director of the Canadian Institutes of Health Research Institute of Aging 1

2 The World is Aging and Canada as Well A Demographic Inversion Statistiques Canada,

3 The World is Aging Prevalence of Dementia Approx. 6-8 % Approx % Source Alzheimer Society Canada, 2016 Source: United Nations Department of Economic and Social Affairs, Population Division, World Population Prospects,

4 Longévité/Démence: le cercle vicieux La population vieillit Encore plus pour les plus âgés Principal facteur de risque: âge L incidence s accroit avec âge 4

5 World Alzheimer Report 2015: The Global Impact of Dementia I can think of no other condition that has such a profound effect on loss of function, loss of independence, and the need for care. I can think of no other condition that places such a heavy burden on society, families, communities, and economies. I can think of no other condition where innovation, including breakthrough discoveries, is so badly needed. G8 Dementia Summit, London,

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9 Interventions? 2015 Source: Phipps, Alzheimer Association,

10 Diseases Causing Dementia 2015 Source: Alzheimer Research UK, 2017 Diseases Causing Dementia 2015 Source: Alzheimer Research UK,

11 Dementia: A Trajectory of Challenges 1 Primary prevention 2 Secondary prevention 3 Quality Of life Sperling et al., Alzheimer s & Dementia, 2011 Adapted from Jack et al., Lancet Neurol.,

12 23 Multiple Levels of Interventions Interventions to reduce risk of developing a neurodegenerative disease Vascular component Physical Activity Nutrition,... Other physiological 1 factors Inflammation Primary Links with prevention the process of aging New Perspectives in geroscience 2 Secondary prevention 3 Quality Of life Sperling et al., Alzheimer s & Dementia, 2011 Adapted from Jack et al., Lancet Neurol.,

13 Aging is the Nexus of Chronic Diseases in Aging 13

14 Geroscience Geroscience seeks to understand the molecular and cellular mechanisms responsible for aging as a major risk factor and driver of common chronic conditions and diseases of older people. While aging itself is not a disease, the aging process represents a major risk factor for a number of chronic diseases and conditions, including CVD, diabetes, many cancers, arthritis, and frailty, among many others Press Releases NIH-NIA Pointing the way forward in geroscience The Journals of Gerontology Series A, Vol. 71, Issue 11 Nov

15 Multiple Levels of Interventions Interventions to reduce risk of developing a neurodegenerative disease Vascular component Physical Activity Nutrition,... Other physiological 1 factors Inflammation Primary Links with prevention the porcess of aging New Perspectives in geroscience Interventions to delay, slow stop or reverse... Clinical signs Lifestyle Cognition Bilingualisme Cognitives 2 Interventions Secondary prevention The disease itself Pharmacological approaches 3 Quality Of life Sperling et al., Alzheimer s & Dementia, 2011 Adapted from Jack et al., Lancet Neurol.,

16 31 Global costs of dementia will reach US$ 2 trillion by 2030, more than the costs of cancer and diabetes combined Global costs of disease Direct and indirect costs 1, US $, billions Global costs, 2010 Global costs, 2030 Cancer Cardiovascular disease Diabetes Dementia The global cost of dementia by 2030 will exceed: Current GDP of all but the 7 wealthiest countries in the world 2 Two thirds of the current healthcare expenditure in the US % increase % +21% +49% +231% 1. Indirect costs included are: care giving costs (cancer, dementia, ), informal care giving costs (dementia), income losses due to disability and death (cancer, cardiovascular disease, diabetes ) 2. Countries with GDP > $2 trillion are the US, China, Japan, Germany, UK, France, India SOURCES: 1. Bloom, D.E., Cafiero, E.T., Jané Llopis, E., Abrahams Gessel, S., Bloom, L.R., Fathima, S., Feigl, A.B., Gaziano, T., Mowafi, M., Pandya, A., Prettner, K., Rosenberg, L., Seligman, B., Stein, A.Z., & Weinstein, C. (2011). The Global Economic Burden of Noncommunicable Diseases. Geneva: World Economic Forum. 2. Alzheimer's Disease International, World Alzheimer's Report 2015: Global Impact of Dementia 3. International Monetary Fund, World Economic Outlook Faststats, National Centre for Health Statistics, Centre for Disease Control and Prevention 1 CVD = cardiovascular disease 2=5 year cancer prevalence Far less is spent on public sector dementia research than on other major diseases Less is spent on dementia research than on other major diseases Research spend per disease as a % of total research spend Research spend on disease per prevalent case Research spend on disease per $ spent on care CVD 1 % total research spend Cancer 6,8% CVD 1 3,6% Diabetes 2,6% Dementia 1,4% Research spend per prevalent case Cancer 2 3.7% N/A Diabetes 0.1% Dementia 0.5% Cancer Dementia Research spend for $ spent on health and social care 32 SOURCE: Research spend from (Dimensions database), cost of care data (1. Bloom, D.E., Cafiero, E.T., Jané Llopis, E., Abrahams Gessel, S., Bloom, L.R., Fathima, S., Feigl, A.B., Gaziano, T., Mowafi, M., Pandya, A., Prettner, K., Rosenberg, L., Seligman, B., Stein, A.Z., & Weinstein, C. (2011). The Global Economic Burden of Noncommunicable Diseases. Geneva: World Economic Forum.2. Alzheimer's Disease International, World Alzheimer's Report 2015: Global Impact of Dementia) CVD 1 Diabetes 0,4% 0,7% 0,9% 4,1% 16

17 33 Dementia has significantly less clinical trial activity than cancer or diabetes Number of trials by phase per disease area 1 Thousands of trials, started between 2013 and Cancer Phase 0 Phase II Phase IV Phase I Phase III 12.3 Diabetes 1.9 Dementia 0.5 Total enrollment by phase in a disease area 2 Thousands of patients Cancer 1,668 Diabetes 514 Dementia Trials started between 2013 and 2016; restricted to trials with a specified phase (phase 0 phase IV) 2 Dementia defined as Senile, Frontotemporal, HIV associated, Lewy body, Parkinson and vascular dementia. Diabetes defined as Diabetes mellitus (all types). Cancer defined as Neoplasms (all types). SOURCE: Cortellis Clinical Trials Feb 2017 Only 2% of drugs in phase I-III development are focused on dementia Cancer Percentage of drugs in phase I III development by therapeutic area %, Extracted November 2014 and February % Cardiovascular 5% Diabetes 3% Dementia 2% 17

18 Still Looking for Successes In the decade of 2002 through compounds were assessed in 413 trials for AD Of the agents advanced to Phase 3 (and excluding those currently in Phase 3), one was advanced to the FDA and approved for marketing (1.8%). Excluding the 14 compounds currently in Phase 3, the overall success rate for approval is 0.4% (99.6% attrition) This is among the lowest for any therapeutic area J. Cummings, LIVING Alzheimer s LONGER diseaseliving drug-development BETTER pipeline: few candidates, frequent failures. Alzheimer's Reserach & Therapy. Pas encore de véritable succès J. Cummings, LIVING Alzheimer s LONGER diseaseliving drug-development BETTER pipeline: few candidates, frequent failures. Alzheimer's Reserach & Therapy. 18

19 Between more was spent on amyloid basic science research than on the other major mechanisms combined Basic science research funding 1 by mechanism of disease, US$ million, Amyloid Tau Neuro protection Synuclein Inflammation TDP Total Basic science research includes research with HRCS RAC codes 1 (Underpinning research) and 2 (aetiology) 1. SOURCE: Dimensions Database, extracted February Dimensions is a global research award database covering around 200 funders and over $900bn in historical awards 3 38 Most trials don t report reasons for suspension, withdrawal or termination of dementia trials but where they do, recruitment problems are the most important cause Reasons for terminating Reasons for trials, termination % (n=129) of trials (n = 129) Trial results (efficacy or safety concerns) 15 Other reasons 1 9 Data not required 5 Recruitment problems Not reported 1 Other reasons = staff attrition and organisational problems, loss of funding, study revision, and study objectives met SOURCE: Long R, Finding a Path for a Cure for Dementia, July 2015; UK Department of Health, Office of Heath Economics, Dementia: The R&D landscape, July 2015 based on data extracted from IMS R&D Lifecycle Focus Database 19

20 Dementia researchers are less connected with each other than in other diseases SOURCE: Pubmed, Visone, McKinsey analysis 40 Fewer researchers who are central to the network than in other diseases SOURCE: Pubmed, Visone, McKinsey analysis 20

21 Lancet Neurology - Priorities Develop and validate biomarkers including biological, genetic, behavioural, and cognitive markers for neurodegenerative brain diseases causing dementia, to identify similarities and differences between diseases and dementia subtypes, and assess progression from premanifest (presymptomatic) to late-stage diseases Diversify therapeutic targets and approaches (eg, multi-mecanisms pharmacological and non-pharmacological interventions) Understand the contributions of vascular conditions to neurodegenerative diseases causing dementia Identify underlying mechanisms of resilience to neurodegenerative diseases causing dementia at all stages (neuroprotection) Optimise individualised therapeutic strategies Understand the role of inflammation and of the immune system in the initiation/onset and progression of neurodegenerative diseases that lead to dementia Multiple Levels of Interventions Interventions to reduce risk of developing a neurodegenerative disease Vascular component Physical Activity Nutrition,... Other physiological 1 factors Inflammation Primary Links with prevention the porcess of aging New Perspectives in geroscience Interventions to delay, slow stop or reverse... Clinical signs Lifestyle Cognition Bilingualisme Cognitives 2 Interventions Secondary prevention The disease itself Pharmacological approaches Interventions for... better health services homecare Integration of care En of life Better support/education 3 Caregivers Health professionnals Better integration in society Social participation Quality Of life Sperling et al., Alzheimer s & Dementia, 2011 Adapted from Jack et al., Lancet Neurol.,

22 Risk factors Cause Model QCICIDH (1991) Organic System Impairment Capacity Disability Environment Obstacles Handicap situation Social articipation Liefstyle e.g. Work Family 22

23 Risk factors Cause Model QCICIDH (1991) Organic System Impairment Capacity Disability Environment Obstacles Handicap situation Social articipation Liefstyle e.g. Work Family 23

24 In Conclusion Interventions for individuals living with dementia or their family should be at all levels Despite efforts to eradicate diseases causing dementia, number of people living with dementia will be important over the coming years Programs to prevent risk of developing disease and of developing clinical symptoms are the most efficient to date But interventions must also include caregivers and optimize social inclusion The Dementia Challenge: Where We Are and Where We Are Heading 24