A list of more than 80 compounds in clinical trials for Alzheimer’s disease, released by PhRMA, inevitably brings to mind all those that failed previously. But researchers view the new list as a source of hope, increasingly confident a breakthrough may be among them.
Alzheimer’s News Today spoke to two Alzheimer’s experts about expectations for these current studies. In those interviews, it became clear that — in contrast to what most people assume — collaboration plays an important role in pharmaceutical company work in this field.
Academic institutions are also involved in these collaborative efforts. And, in their midst, the Alzheimer’s Association is a driving force, funding collaboration initiatives and offering scientists a platform to come together to discuss research difficulties and progress.
What are these initiatives? And how do they help advance potential treatments for Alzheimer’s disease?
PhRMA is a group of major U.S. pharmaceutical companies that, among other things, works to modernize drug development processes. In the field of Alzheimer’s research, this translates to two major collaborative enterprises — the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Accelerating Medicines Partnership – Alzheimer’s Disease (AMP-AD).
These projects involve more than pharma. Both also engage the National Institutes of Health (NIH), other federal agencies, and nonprofit organizations. The U.S Food and Drug Administration (FDA) is involved in AMP-AD.
ADNI is an effort to identify the earliest signs of Alzheimer’s disease through the use of biomarkers — including brain scans, blood and spinal fluid tests — and cognitive assessments that compare healthy older adults with those with mild cognitive impairment or some stage of Alzheimer’s disease.
Researchers believe this work will speed up new treatment development by identifying biomarkers. These measurements can be used to identify those patients most likely to benefit from a treatment, and to assess if and how well an investigative drug is working.
Data collected in the program are available to scientists free of charge, and both pharmaceutical and academic researchers have turned to this data in discussions of drug development work, said Dr. Matthew Kennedy, director of Early Discovery, Neuroscience, at Merck and a PhRMA representative.
As an example, Kennedy spoke of how companies have used initiative data in designing aspects of clinical trials, like their duration.
AMP-AD is also focusing on biomarker development, providing trials with supplemental measures of effectiveness. And researchers are building a database with molecular information from patients to guide future studies.
Pharma also supports development efforts by providing additional support to academic research. For instance, a group of Harvard Medical School scientists, led by Dr. Reisa Sperling, is running several trials trying to prevent Alzheimer’s disease in people with brain plaque but no cognitive symptoms. These trials are testing various drugs in collaboration with the companies that produce them.
The Dominantly Inherited Alzheimer Network (DIAN) is another such example. The study at Washington University benefited from data gathered in Eli Lilly’s failed solanezumab trial, said Dr. Dean Hartley, director of scientific initiatives at the Alzheimer’s Association.
Safety data from Lilly’s trial is allowing DIAN researchers to test higher doses of the compound in its study (NCT01760005) of people at genetic risk for Alzheimer’s, along with drugs from Roche and Janssen — a venture that ably demonstrates how partnerships can drive discovery.
The Alzheimer’s Association’s role
As a nonprofit organization, the Alzheimer’s Association is working on a broader scale to bring funding and researchers together.
Among its many projects, the group funds a $3 million trial where scientists at the University of Southern California and Washington University study biomarkers in vascular dementia, as these markers might also be of use in Alzheimer’s.
In addition to financial support, the association also promotes open discussion of ideas among company scientists.
In one such effort, which it calls the Research Roundtable, the association brings experts from various pharmaceutical companies together in closed-door meetings to debate and share aspects of research processes and methodology.
“It’s a precompetitive environment where people talk about problems in the field itself,” Hartley said.
The initiative, which started in the mid-2000s with researchers from four companies, now engages 27 pharmaceutical firms. Their meetings have already had an impact, Hartley said, mentioning their interaction with the National Institute on Aging and others that led to a 2011 upgrade of Alzheimer’s diagnostic criteria.
The very complexity of Alzheimer’s disease brings companies together, driven by a common conviction that success for one benefits all — and failure hurts the whole field.
“I think companies want to see other companies succeed because … it will mean [they] should continue,” too, Hartley said.
Registries and beyond
Although research into Alzheimer’s has gone on for decades, more awaits to be discovered than is already known.
In illnesses like cancer and heart disease, large patient registries help to provide crucial disease information. The Alzheimer’s Association believes that large national or global registries will also be key to advancing the Alzheimer’s field.
Registries now underway in the U.S. are somewhat small and scattered, Hartley said, largely the work of academic groups. They also tend to include mainly people of European descent, although other ethnicities are at higher risk. So he and his fellows at the association are pushing for a major national — or global — Alzheimer’s registry.
The association also supports work on datasets that may differ from classical patient registries. One example is the TriBEKa consortium, a European collaboration between researchers from Barcelona, Edinburgh in the U.K., and Karolinska in Sweden, that started an imaging database now available to researchers worldwide.
And the association launched what it calls a cloud-based computing system, the Global Alzheimer’s Association Interactive Network (GAAIN). The intention is to create a global platform for Alzheimer’s data that can be mined by researchers exploring various disease aspects. GAAIN already holds information about some 400,000 people, but with new collaboration efforts in the pipeline, the hope is that number will increase.
Among the many aims of registry studies is the possibility of learning more about lifestyle habits that add both to disease risk and avoidance. Researchers increasingly believe that lifestyle choices are instrumental in tipping some people toward an Alzheimer’s diagnosis.
Among such registries is the Brain Health Registry — an initiative at the University of California San Francisco that allows people to share data about their brain health in a voluntary and prospective manner, letting researchers in on information that may be key to preventing the disease from ever developing.
What lifestyle choices might be best are also fundamental questions in Alzheimer’s. For potential answers, the Alzheimer’s Association is launching the U.S. POINTER study.
The $20 million randomized, controlled, interventional trial — expected to launch in 2018 — will recruit 2,500 older people with a high dementia risk. They will undergo a broad intervention program that includes exercise, nutrition, cognitive training, and management of other illnesses thought linked to Alzheimer’s, like metabolic disease. A control group will receive health education and support. Maybe, one day, it will turn out that lifestyle changes are more effective in stopping Alzheimer’s than drugs, Hartley said.
Until then, knowledge of this ongoing and collaborative work adds context to Kennedy and Hartley’s optimism that a breakthrough in Alzheimer’s research may be around a not-too-distant corner.