Alzheimer's Prevention Initiative

On 26 January 2010, at an ordinary airport hotel in Phoenix, Arizona, an extraordinary gathering unfolded. High-level representatives of 19 different pharma, biotech, and medical companies from across the U.S. and Europe – businesses that compete fiercely for the same market – spent the entire day cooped up in one room. There they engaged in a searching, at times surprisingly candid, discussion with academic research leaders, funders, and regulatory and statistics experts. Their topic? How they could set aside their competition in order to advance a shared vision of testing candidate drugs in people who are at imminent risk for Alzheimer’s disease (AD) but have no symptoms. In other words, these are future patients who, pathologically speaking, may already have AD but as yet without the dementia that epitomizes the disease in most people’s minds. AD prevention has become a favorite buzzword of late, but approaching this goal with clinical trials of candidate AD drugs is difficult to do. This meeting represented perhaps the most advanced effort to date to actually pull it off. Called the Alzheimer’s Prevention Initiative (API), the effort is the brainchild of Eric Reiman and Pierre Tariot at the Banner Alzheimer’s Institute and the Arizona Alzheimer’s Consortium in Phoenix, Arizona. They and their Banner colleagues had invited the group of 50 people to this meeting. Riding the collaborative wave created by previous shared efforts such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the Alzheimer’s Disease Cooperative Study (ADCS), and the Dominantly Inherited Alzheimer Network (DIAN), these scientists are trying to build a coalition of academic and industry leaders with other stakeholders to begin, already in 2011, biomarker-driven drug trials initially in two separate sets of people who, based on their genetic status and age, are at the highest imminent risk of symptomatic AD. One group is middle-aged adult relatives of a large extended family near Medellin, Colombia, who are stricken with a deterministic early-onset presenilin 1 mutation. The other group are people in their sixties and seventies in the U.S., and potentially abroad, who carry two copies of the ApoE4 gene. The API has joined forces with DIAN, the international network for families with dominantly inherited (i.e., AβPPand PS-mutant) AD, which is already enrolling for an observational study and has begun planning its own drug study to offer to DIAN participants in the next year or two, as well. “My dream is to get parallel preclinical trials going in these high-risk people and also the general population. We want to launch an era of prevention research where the field at large evaluates pre-symptomatic treatments rigorously and rapidly in randomized clinical trials,” said Reiman. If this seems ambitious, that is because it is. Talking about the benefits of prevention of AD is stating the obvious, but the day’s discussions highlighted the fact that many hurdles remain. They also made clear that pharma’s pre-competitive spirit comes to a cold stop when the discussion broaches their own or their competitors’ drugs. Even so, most attendees urged Reiman and Tariot to press on with their proposal and indicated that they would want to be part of it. That is in part because concern is growing in academia and industry that the conventional mode of testing drug candidates in people with mild to moderate AD using parallel-arm study designs may not produce impressively effective therapies any time soon. There is a palpable concern that this conventional treatment trial design could sink the prospects of what might have been a respectable pre-symptomatic therapy before a way is