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© Copyright 2016 Quintiles
“2016 – is this the end of the 100 year plus battle
against AD”?
Dr Lynne Hughes and Susie Boyc...
2
• Clinical trials are the scientific process for
measuring whether new drugs are safe and
effective.
• James Lind, physi...
3
Drug
discovery
Pre clinical
testing
Phase I Phase II Phase III
Licensing
Approval
4.5 years 5.5 years 7 years 8.5 years ...
4
The Rocky Road of Research in Alzheimer’s Disease
So, what is Alzheimer’s Disease?
1906 AD was 1st described by German n...
5
First Documented Case of Premature Disease of Forgetfulness
50-year old woman from Germany in 1901
6
7
Why is this a problem?
Key facts: 2013 World Alzheimer’s Report
Global Prevalence of dementia
46, 8 million in 2015
For ...
8
 Most costly in U.S.
direct health
expenditures
 Most costly in
informal care costs
 Fastest
accelerating
disability ...
9
 Increasing longevity
is driving the
incidence of
Alzheimer's
 There are 3 super-
aged countries
today and there will
...
10
• Dementia is financially debilitating for patients and their families.
• Dementia costs families nearly double the amo...
11
11
Drug Development in AD
Last 20 years 101 negative Ph III trials…… success rate of 0.4 %
1993-2001 Approvals
• 1993 T...
12
12
The Alzheimer's’ Landscape
Citeline Export, May 2016
13
Why we need to continue trying and to succeed
35% of people age 60 or older are most afraid of developing Alzheimer’s D...
14
Current Dementia Drug Discovery Paradigm is Not Working
Challenges with
dementia drug
discovery:
1.Target Identificatio...
15
What are the Current Treatments?
They are only used after the patient is diagnosed with AD
Limited in time and efficaci...
16
• Prodromal AD – before a patient has signs & symptoms of AD
› Aged 50+
› Episodic memory problems – where did you leav...
17
2016 Modeling: Registry Statistics
Example of registry recruiting
On line 6,750,000 Registrants
675,000 Subjects Referr...
18
The Continuum of AD and Normal Aging
TRIAL SUBJECT
OF TODAY
TRIAL
SUBJECT OF
TOMORROW
19
• The challenges:
› Only trial drugs available
› Very difficult to identify suitable patients
› Aim is to prevent the d...
20
Young Subjects People
Trial Elderly Subject Trial G7 EPAD
• Treatment of the children of
AD people with a confirmed
gen...
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Lynne Hughes and Susie Boyes

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2016 - Is this the end of the 100 years plus battle with Alzheimer's Disease? Dr Lynne Hughes and Susie Boyes present at Bringing Projects to Life conference #eVa21

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Lynne Hughes and Susie Boyes

  1. 1. © Copyright 2016 Quintiles “2016 – is this the end of the 100 year plus battle against AD”? Dr Lynne Hughes and Susie Boyce, 16 June 2016 Note: This is our personal view not an official company view.
  2. 2. 2 • Clinical trials are the scientific process for measuring whether new drugs are safe and effective. • James Lind, physician (1747) pioneered the field of clinical research > Discovery Citrus fruits prevented scurvy. • Sir Austin Bradford Hill, epidemiologist (1946) 1st randomised controlled trial (RCT) Streptomycin to treat tuberculosis • Regulatory agencies have used clinical trials ever since to determine whether a new drug is ready for the public. • 1019 Novel drugs approved by the FDA Introduction to Clinical Trials
  3. 3. 3 Drug discovery Pre clinical testing Phase I Phase II Phase III Licensing Approval 4.5 years 5.5 years 7 years 8.5 years 11 years 12.5 years £436 million £533 million £710 million £916 million £1.1 billion £1.15 billion 5,000 – 10,000 candidates 10-20 candidates 5-10 candidates 2-5 candidates 1-2 candidates 1 medicine Drug Development Process Reference source: abpi publication Time to flourish Inside innovation; the medicine development process
  4. 4. 4 The Rocky Road of Research in Alzheimer’s Disease So, what is Alzheimer’s Disease? 1906 AD was 1st described by German neuropathologist: Alois Alzheimer A devastating progressive neurological disease characterized by progressive loss of memory and cognitive functions, decline in functional capacity and alteration in behavior. We still do not know the cause The only disease in the top 10 leading causes of death that cannot be prevented, cured or even slowed down.
  5. 5. 5 First Documented Case of Premature Disease of Forgetfulness 50-year old woman from Germany in 1901
  6. 6. 6
  7. 7. 7 Why is this a problem? Key facts: 2013 World Alzheimer’s Report Global Prevalence of dementia 46, 8 million in 2015 For 2015, we estimate over 9.9 million new cases of dementia each year worldwide, implying one new case every 3.2 seconds. This new estimate is almost 30% higher than the annual number of new cases we estimated for 2010 131.5 million in 2050 6-8% of all persons older than 65 have AD 30% of population over 85 have AD Less than 10 million AD patients are treated Requiring Care: Half of all dementia sufferers 80% of nursing home patients This is an increasing Global Challenge with an aging population
  8. 8. 8  Most costly in U.S. direct health expenditures  Most costly in informal care costs  Fastest accelerating disability burden  The cost of AD globally is $800B1 8 77 102 109 65 75 85 95 105 Cancer Heart Disease AD Direct Health Expenditures (billions) Alzheimer’s Disease International. World Alzheimer Report 2015. http://www.alz.co.uk/research/world-report-2015. Accessed February 2016
  9. 9. 9  Increasing longevity is driving the incidence of Alzheimer's  There are 3 super- aged countries today and there will be 30 within the next 15 years  Only major killer without a means of slowing, preventing or curing 9 46.8 74.7 131.5 2015 2030 2050 AD Patients (Millions) Alzheimer’s Disease International. World Alzheimer Report 2015. http://www.alz.co.uk/research/world-report-2015. Accessed February 2016
  10. 10. 10 • Dementia is financially debilitating for patients and their families. • Dementia costs families nearly double the amount of other major diseases in the last 5 years of life. • Treatment involves many out-of-pocket expenses that use, on average, almost one third of a patient’s wealth and impoverish about half of U.S./ W Eu dementia patients. Impacts on Patients and Families Source Time 2015, Annals of Internal Medicine 2015
  11. 11. 11 11 Drug Development in AD Last 20 years 101 negative Ph III trials…… success rate of 0.4 % 1993-2001 Approvals • 1993 Tacrine (Cognex) first one approved now off market due to safety • Nov 96 Aricept approved • 2000: Rivastigmine • 2001 Galantamine 2003 Approvals • Memantine 2006-2008 Failures • Serotonin 6 receptor antagonists halted after phase 2 • Leuprolide • Tramiprosate • Flurizan Other Failures • NSAID’s • Latrepirdine • Histamine H3 receptor antagonists 2011-2012 Failures • Gamma secretases Semagacestat, Avagacestat, Elan: AN1792 • Amyloid immunoRx Bapineuzumab • Solanezumab (+/-) • Vaccination AD02 • H3 receptor antagonist SAR 110894 2013-2014 Failures • Insuline path: Rosiglitazone, Atorvastatin, Simvastatin • Amyloid: Gantenerumab*, Crenezumab* • Passive immunization: IVIG • Beta Secretase: LY2886721 • ABT126 Nicotinic • PRX3140 Ser4 Rec and terminated in AD AcEi NMDA receptor antagonists 2015 Failures • MAO-Bi Sembragiline failed phase 2 on primary efficacy
  12. 12. 12 12 The Alzheimer's’ Landscape Citeline Export, May 2016
  13. 13. 13 Why we need to continue trying and to succeed 35% of people age 60 or older are most afraid of developing Alzheimer’s Disease or dementia (cancer 23%) Alzheimer’s Disease International. World Alzheimer Report 2015. http://www.alz.co.uk/research/world-report-2015. Accessed February 2016
  14. 14. 14 Current Dementia Drug Discovery Paradigm is Not Working Challenges with dementia drug discovery: 1.Target Identification: Complicated disease, poorly understood 2.Discovery and Development: The majority of dementia programs narrowly focus on amyloid beta and tau approaches 3.Clinical Development: High cost, complexity, risk, and length of clinical trials Summary of AD Trials 2002-20121 1Quintiles database using internal de-identified data
  15. 15. 15 What are the Current Treatments? They are only used after the patient is diagnosed with AD Limited in time and efficaciousness On the market for almost 20 years There are currently only symptomatic treatments available to patients: • They do not modify the course of the disease, but provide short-term improvements to a patient and delay briefly putting a patient in an institution
  16. 16. 16 • Prodromal AD – before a patient has signs & symptoms of AD › Aged 50+ › Episodic memory problems – where did you leave your keys? • Where are these people? › At home, in the community. › No real symptoms › No-one self-identifies with potentially having a disease • How to find them? › Advertising › Digital outreach › Public awareness • What happens? › We get the “worried well” › We spend a lot of time & money screening for the “real” patients. Now Let’s Look at Earlier Diagnosis
  17. 17. 17 2016 Modeling: Registry Statistics Example of registry recruiting On line 6,750,000 Registrants 675,000 Subjects Referred 27,000 Subjects Screened 22,500 Subjects Needed 4500 Subjects Randomized Online Registry • Demographics • Cognition testing online • Family History • 10 % referred to a site Referral and Prescreening • BHR and Healthy Brains referred to sites • Only 4 % registrants get screened Current Registry Status • To recruit the estimated 4500 subjects in 2016, • Nearly 7 million registry participants are needed
  18. 18. 18 The Continuum of AD and Normal Aging TRIAL SUBJECT OF TODAY TRIAL SUBJECT OF TOMORROW
  19. 19. 19 • The challenges: › Only trial drugs available › Very difficult to identify suitable patients › Aim is to prevent the disease developing or progressing • Intervene earlier at the prodromal stage • Innovative clinical trial design acceptable for regulators • Optimal and pragmatic execution of studies: › Right study design with right duration › Acceptability of patients and caregiver of invasive procedures (CSF) › Decrease of inter-rater variability (certification of raters) The Future: Early Intervention & DMDs FIRST READ-OUT OF A POTENTIAL NEW THERAPY Q4 2016!!
  20. 20. 20 Young Subjects People Trial Elderly Subject Trial G7 EPAD • Treatment of the children of AD people with a confirmed genetic mutation • Tx with 2 experimental drugs & placebo • Treating young people : 25 – 40 – who have no symptoms • Biomarker outcome • NIH sponsored • Most high profile trial in AD in the world • 10 countries, 30 sites, 240 pts • Treatment of 5000+ healthy elderly subjects • Biomarker positive : randomised to pioglitazone or placebo • Biomarker negative : randomised to placebo • Time to develop MCI • 7 countries, 63 sites 6,116 pts • Pan- Eu initiative led by D Cameron and backed by the G7 countries • 24,000 high risk subject virtual registry across Eu • 6,000 extremely high risk subjects in a managed registry • Up to 5 years longitudinal follow up : PET, MRI, Cognition • 1000 subjects “trial-ready” at a given time point • Adaptive design, I-Spy-type trial for such subjects • 16 pharma companies Leading Science Focus on Prevention 1Quintiles database & Clinical trials.gov

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