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Saturday, November 16, 2013

Special Blog Post: Highlights from Day One of CTAD

CTAD Highlights November 14, 2013

San Diego, California. The sixth annual Clinical Trials in Alzheimer's Disease (CTAD) conference opened today with the presentation of the first ever CTAD Lifetime Achievement Award in Alzheimer's Disease Therapeutic Research to Dr. Russell Katz, the recently retired director of the Food and Drug Administration’s (FDA) Division of Neurology Products.

Paul Aisen, M.D., Director of the Alzheimer's Disease Cooperative Study and Professor of Neurosciences at the University of California, San Diego, introduced Dr. Katz as “our tireless friend and leader at the FDA,” noting that under Dr. Katz’s leadership, the FDA has become an active partner with academia and industry in the AD drug development effort. “The optimism that many of us feel today is due in good part to our collaborative relationship with the FDA that has allowed the field to evolve towards effective therapy,” said Dr. Aisen.

“I have always thought that the best way to win this fight is for all relevant parties to get together,” said Dr. Katz. The award, he said, acknowledges the fact that the FDA is a pivotal partner in this fight. “The Agency’s commitment to winning this fight is rock solid,” he added.

A decade of frustration
Dr. Aisen followed the award presentation with a keynote address describing the challenges the field has faced over the past 10 years and the recent developments that he believes will lead to future success. “It’s been a difficult and frustrating decade,” said Dr. Aisen. No new drugs have been approved during this period for the treatment of AD despite hundreds of trials. One reason for these repeated failures is that the field has moved away from treating symptoms in late stage dementia towards trying to modify the underlying disease process in earlier stages of the disease such as a pre-dementia stage known as Mild Cognitive Impairment (MCI). Proving that a drug is effective in patients with MCI is complicated by the heterogeneous nature and gradual progression of the disorder, which results in a need for long studies and huge number of subjects.

However, recent proposed changes in the way the FDA will evaluate clinical trials should make it possible to design trials that can demonstrate efficacy in earlier stages of the disease. “We are confident that we are more likely to succeed because of these changes in the clinical trials approach,” said Dr. Aisen. “We even look to move earlier – to the asymptomatic or preclinical AD stage. Ultimately, our eye is on primary prevention.”

One of the essential elements of a preclinical AD trial will be the inclusion of biomarkers that will enable the classification of people with MCI according to how likely it is that they are on the AD trajectory. Ronald Petersen, M.D., Ph.D., Director of the Mayo Alzheimer's Disease Research Center described studies done both in research and community settings that support the notion that markers of amyloid deposition and neurodegeneration can differentiate people with MCI into four groups according to the likelihood (high, intermediate, uncertain, or unlikely) that their cognitive impairment is due to Alzheimer's pathology. Although there are several different sets of criteria that have been proposed for the diagnosis of preclinical AD, Dr. Petersen said that there is more consistency between them that disagreement. All of these criteria rely to some extent on the use biomarkers, and recent studies from several research groups corroborate that the staging system proposed in these different criteria seem to be working. Moreover, recent data also indicate that there are clinical changes that can be detected in the preclinical stage. “Even in the normal aging stage there are data indicating subtle clinical changes,” he said, echoing a point made by Dr. Aisen earlier that cognition may be the best biomarker of Alzheimer's pathology.

Other biomarkers have also recently emerged that seem to provide additional insight into the pathological process that underlies AD and other forms of dementia. One that has generated intense interest is tau imaging. Tau is the protein that forms the neurofibrillary tangles that are seen at autopsy in the AD brain. At CTAD, researchers from Japan and the United States reported progress in developing a class of agents that are used with positron emission tomography (PET) scanning to visualize tau in the brain. Although the results are still considered very preliminary, investigators expressed optimism that these agents could lead to a better understanding of the neurodegenerative process in the AD brain. Importantly, these early results indicate that tau imaging may be able to track progression over time and even possibly treatment effects.

The next generation of clinical trials
Eric Reiman, M.D., Chief Executive Officer of Banner Research said, in another keynote address, that the time has come to establish a new era in AD prevention research. Dr. Reiman leads the Alzheimer's Prevention Initiative (API), one of four large prevention studies getting underway in 2013. API and the other three studies: the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), the Anti-Amyloid treatment of Asymptomatic AD (A4), and the TOMMorrow trials are all selecting populations with a high likelihood of developing the disease during the trial period. Testing people close to this transition point is seen as the best way to assess whether a treatment slows the disease.

All of these studies are incorporating a treatment trial with extensive biomarker assessments in order to learn more about how biomarker behave as well as how they relate to clinical outcomes. And in order to ensure that findings from the studies can be compared and shared, API, DIAN and A4 have joined forces under the umbrella of the Collaboration for Alzheimer's Prevention (CAP).

“We are in uncharted territory,” said Dr. Reiman. “I would argue that these complementary trials are truly complementary and greater than the sum of the parts.”

About CTAD
Since 2008, CTAD has been a conference organized and planned by Alzheimer’s disease (AD) clinical researchers for AD clinical researchers. CTAD embraces the organizing committee mandate to maintain CTAD’s unique role in AD research: To provide a substantive, clinical research-oriented conference and an annual opportunity for the world’s preeminent clinical researchers to engage in both formal and informal exchanges of views. CTAD’s ongoing commitment to providing a relatively intimate forum has resulted in the conference’s reputation of facilitating and fostering international collaboration in AD clinical research matters. More information is available at
Author: Paul Aisen MD at 9:13 AM 0 Comments

Friday, November 01, 2013

New Tracer Approved by FDA to Identify Beta Amyloid in the Brain

Dear readers,

Last week the FDA approved Vizamyl, or flutemetamol, a tracer that binds to amyloid plaques. As readers of this blog will recall, a positron emission tomography (PET) scan is an imaging test that uses a radioactive substance (called a tracer) to bind to specific targets in the brain. In the case of Vizamyl, it works by attaching to beta amyloid, thereby making the amyloid plaques visible on a PET scan. Vizamyl is now the second diagnostic drug approved by the FDA for visualizing beta amyloid on a PET scan. Last year, Amyvid (florbetapir) was approved to help evaluate for the presence of amyloid plaques. Increased levels of beta amyloid plaque are a defining pathological feature of Alzheimer's disease.

As with Amyvid, Vyzamil is not meant to replace the diagnostic tools currently used in the evaluation of AD and other dementias, but rather to assist physicians in identifying the underlying cause for the cognitive decline. For example, in patients with fronto-temporal dementia, vascular dementia, progressive supranuclear palsy, Parkinson’s disease dementia, Lewy body dementia, and cortico-basilar ganglionic degeneration, one would expect a negative amyloid PET scan.

The Society for Nuclear Medicine and the Alzheimer’s Association have recommended guidelines to assist physicians in determining which patients are appropriate for brain amyloid imaging. Appropriate patients for brain amyloid imaging are those who have met the core elements and meet one of the following appropriate indications:

1. Patients with persistent or progressive unexplained mild cognitive impairment
2. Patients who satisfy the core clinical criteria for AD due to any cause with an atypical course
3. Patients with progressive dementia and an atypical early age of onset (<65 years of age)

It is important to keep in mind, that although Amyloid PET scans are FDA approved, and currently in use in many AD clinical trials, they are not covered by insurance, including Medicare, and costs for PET scans, which are about $3,000, are currently “out of pocket.” However, with more tracers available, there may be a reduction in cost and perhaps consideration by insurance companies to cover this type of imaging according to the guidelines listed above.

Thanks for reading.

Michael Rafii, MD, PhD
Director, Memory Disorders Clinic
Associate Medical Core Director
Alzheimer’s Disease Cooperative Study
University of California San Diego
Author: Michael Rafii MD,PhD at 9:53 AM 0 Comments

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The Alzheimer's Disease Cooperative Study (ADCS) was formed in 1991 as a cooperative agreement between the National Institute on Aging (NIA) and the University of California, San Diego. The ADCS is a major initiative for Alzheimer's disease (AD) clinical studies in the Federal government, addressing treatments for both cognitive and behavioral symptoms. This is part of the NIA Division of Neuroscience's effort to facilitate the discovery, development and testing of new drugs for the treatment of AD and also is part of the Alzheimer's Disease Prevention Initiative.

The ADCS was developed in response to a perceived need to advance research in the development of drugs that might be useful for treating patients with Alzheimer's disease (AD), particularly drugs that might not be developed by industry.