The New Era of Alzheimer’s Prevention Treatment Trials

Jessica B. Langbaum, PhDPrincipal Scientist, Banner Alzheimer’s Institute

Associate Director, Alzheimer’s Prevention InitiativePhoenix, Arizona

Alzheimer’s

Debilitating

Incurable

Devastating

Not a normal part of aging

Alzheimer’s vs. Dementia

Understanding Alzheimer’sThis neurological disease causes devastating damage, ultimately robbing an individual of mental and physical capacity

Its cause is still unknown, but a leading scientific hypothesis links Alzheimer’s to excessive build-up of the protein amyloid in the brain

Some people are at higher risk of developing Alzheimer’s because of their genetic background

Understanding Alzheimer’sSubtle changes begin taking place in the brain years before the first problems with memory or thinking appear

Advanced imaging, biomarker techniques and sophisticated cognitive measures can detect these changes in brain structure and function

Promising treatments may need to be started at the pre-symptomatic stage of the disease to have their most profound effect

Alzheimer’s by the Numbers

Someone is diagnosed with Alzheimer’s every 6.9 seconds in this country

5.4 million Americans are currently affected by Alzheimer’s

Alzheimer’s is the 6th leading cause of death in the United States

Alzheimer’s is the only top 10 cause of death that cannot be prevented, treated or cured

Alzheimer’s cost of care is projected to reach $1.1 trillion by 2050

77% of U.S adults are concerned

about personal memory loss,

while 85% are concerned over

memory loss in loved ones

Alzheimer’s Prevention Trials – why now?

The urgent need

Suggested but unproven “healthy lifestyle” interventions

Investigational Alzheimer’s disease modifying treatments

“Too little too late”

Biomarkers & sensitive cognitive measures

Preclinical Alzheimer’s Disease Treatments: a proposed definition

“interventions started before the onset of cognitive decline and intended to postpone the onset, reduce the risk of,

or completely prevent Alzheimer’s symptoms”

Reiman et al, Biomarkers Med 2010

Overview of Planned Alzheimer’s Prevention Trials Starting in 2013

Trial Participants Where? Treatment Trial Specifics

ADCS “A4” •1,000 • Age 70 - 85• Amyloid +

•500 amyloid- in natural history study

•US TBN1000 amyloid+ randomized 1:1 treatment to placebo

•3 year clinical trial•Interim analysis at 18months for biomarkers

API • 300 in Colombia• ~ 30 in US

• Age 30-60 • ADAD kindred

•US •Colombia

crenezumab (Genentech) 200 carriers randomized 1:1 treatment to placebo; 100 noncarriers to placebo

•5 year clinical trial•interim analysis at year 2

DIAN • 240 • Age -15 to +10 years

compared to parent age of onset

• ADAD kindred

•US•Europe•Australia•Others may be added

• gantenerumab (Roche)• solanezumab (Eli Lily)Potential:• BACE inhibitor (Eli Lilly)•160 carriers randomized to 3 drug arms or placebo; ~80 noncarriers to placebo

•2 year biomarker trial•will decide which treatment to continue for 3 year trial

Zinfandel / Takeda

•4, 000 • Age 62-83• TOMM40+

•US • pioglitazone (Takeda)

Amyloid+ (n =500)

TREATMENT ARM

Amyloid+(n =500)

PLACEBO ARM

Amyloid-(n= 500)

Natural History Study

RCT PORTION OF STUDY

Individuals age 70-85 screened with amyloid PET

ADCS “A4” Trial of a TBN Anti-Amyloid Treatment

RCT PORTION OF STUDY

ADAD Mutation Kindred Members -15 to +10 years from parent age of dementia onset

DIAN Treatment Trials

ADAD carrier (n = 40) gantenerumab

ADAD carrier (n = 40) solanezumab

ADAD carrier (n = 40) BACE (added later)

ADAD carrier (n = 40) Pooled placebo

ADAD non-carrier (n = 80) placebo

COHORT PORTION OF STUDY

Alzheimer’s Prevention Initiative / Genentech Treatment Trial – Colombia*

• 300 participants– 200 carriers, 100 noncarriers– Standard of care is not to disclose genetic

status

• up to 18 months for enrollment• 104-260 week trial in 200 carriers to study

efficacy of treatment by comparing change in in cognition and biomarkers

• Natural history (“cohort study”) of 100 placebo-treated carrier & non-carriers

* A separate US protocol will enroll ~30 carriers and non-carriers in a similar fashion

5 PS1 Mutations in Colombia

Gloria cares for her sister Maria, age 61, who developed AD symptoms in her 40s.

Photograph by Todd Heisler, February 2009, courtesy of the NY Times, with permission

Alzheimer’s Prevention Registry

Inclusive, online community of people who are passionate about advancing research in Alzheimer’s

Designed to help generate critical public awareness around the disease

A shared resource benefiting the general research community and organizations nationwide

People in the Registry may have the opportunity to participate in research studies within their community

• Participants are sent emails informing them of potential study opportunities, but are never any obligation to join a study

• All information is kept confidential and is not shared without your explicit permission

What We Hope to Accomplish

Keep enrollees informed of latest news, advocacy to drive focus on Alzheimer’s

Provide an unprecedented resource of potential study participants for prevention research ,

decreasing enrollment time

Offer valuable resources of simple, easy to understand news in partnership with AlzForum

Our important goal is to register 100,000 people by June 30, 2013

Joining the Registry

Visit www.endalznow.org

Complete this page…

…and this page

And you have joined!

Customize your community

Spread the Word!

Acknowledgments

• Drs. Pierre Tariot, Eric Reiman, Francisco Lopera, Adam Fleisher, Lon Schneider, Ron Thomas and many more from the Alzheimer’s Prevention Initiative

• Drs. Reisa Sperling and Paul Aisen from ADCS “A4”• Drs. Randy Bateman, John Morris and Anne Fagan from

DIAN• Colleagues from the Collaboration for Alzheimer’s

Prevention• Colleagues from Genentech • National Institute on Aging, Geoffrey Beene Gives Back

Alzheimer’s Initiative and Banner Alzheimer’s Foundation