Robert Essner
Chairman and Chief Executive Officer, Wyeth

Remarks at the Visions Roundtable, National Press Club, Washington, D.C.
“Inventing a Better Future: Harnessing Science to Overcome Alzheimer’s Disease”
November 14, 2006

It’s a pleasure to be here today and to share my thoughts on the intersection between science and patient care — in other words, how Wyeth and the private sector research-based pharmaceutical industry are trying to harness science to overcome Alzheimer’s disease.

This is an important time to be thinking about Alzheimer's and evaluating whether we are prepared for the coming epidemic. I say "epidemic" because that's what we're headed for — an epidemic of enormous proportion. I know many of you understand that and have spent your lives dealing with the devastation of this disease.

I'm fairly certain, though, that the population at large does not really see Alzheimer's disease as an epidemic — at least not yet.

What Makes an Epidemic?

Last year, I spoke at the White House Conference on Aging and pointed out that if you were to say the word "epidemic" then, I'd bet most people would have immediately thought about avian flu, the so-called "bird flu." That's because avian flu had received massive attention in the media, and people were genuinely and understandably frightened by the possibility of the disease sweeping the world. With all the intense interest around avian influenza, I sometimes think we have lost sight of the fact that this disease — scary as it is — is only a potential threat that we may or may not actually have to deal with.

The next disease most people would probably think about is HIV/AIDS. Reports in the 1980s on the devastation of AIDS quickly garnered widespread attention. The fear factor of this “new” disease with dramatic mortality rates was extraordinary. Scientific advances and a significant amount of effort across a multiplicity of stakeholders have rendered the threat of AIDS today to be very different from the way it was 10 or 20 years ago. While AIDS does continue to ravage many developing countries, in many parts of the world a diagnosis is no longer an automatic death sentence. Although much remains to be done, in many ways this fact is miraculous. It feeds the imagination with images of a world in which AIDS is no longer an epidemic but a manageable chronic illness. Unfortunately, the same cannot be said about Alzheimer’s disease.

So what is it about avian flu and AIDS that resonates “epidemic”? Is it their impact on the public health or the public’s imagination? Is it the scientific etiology of the diseases or their widespread threat? And why is it that Alzheimer’s does not resonate in the same way?

Is it that AIDS and avian flu are “new” — that they were identified and discovered within our lifetimes? Alzheimer’s disease was first identified 100 years ago. No one alive today remembers a world without Alzheimer’s. I think it’s possible that we’ve simply gotten used to the presence of this disease and that its threat has been somewhat mitigated in the public eye by virtue of its longevity. But that is a mistake. The disease is no less dangerous and carries no lesser burden simply because it predates all of us. If anything, the fact that the disease continues virtually unabated should draw our attention all the more.

Alzheimer’s disease dramatically affects the public health and stirs the public imagination, and we know what its impact will be — we can, in fact, predict with chilling accuracy its incidence and prevalence. We know the horrifying and ultimately fatal course of this illness. We know the collateral damage it does to the families of those who suffer from it — damage that often ironically carries a worse toll than the direct impact of the disease on its victims. And we can project with reasonable precision the enormous financial toll that caring for patients who suffer from it will take on our country's health care budget and our economy.

Many people do not know that Alzheimer's disease is the third most costly disease to treat in the United States. And most do not know that annual Medicare costs for beneficiaries with Alzheimer's are expected to increase 75 percent over the next five years and that federal and state Medicaid spending for nursing home care for Alzheimer’s patients is expected to nearly double by 2025.

The costs of Alzheimer’s disease don’t strike governments alone — they also strike individual families and our nation’s businesses. Over the course of the disease, Alzheimer’s patients and their families spend more than $200,000 on health care per patient. And employers lose approximately $60 billion a year on lost productivity as adult caregivers are forced to leave their jobs — either permanently or on a temporary basis — to care for a family member with the disease.

I think you get the picture.

What is so horrifying about Alzheimer's is not just that it kills but that it is debilitating and dehumanizing. Alzheimer's essentially eats away at the very essence of its victims — not just their physical and mental capabilities but also their personalities and the qualities that make us all human. Yet the general public still does not, by and large, consider Alzheimer’s disease to be an epidemic. But the world’s scientists are starting to do so. They are not just sitting by and watching the devastation approach: Efforts to respond to the epidemic of Alzheimer’s are under way across academia, industry and government.

Now let me tell you our story.

How Science Responds to an Epidemic: Wyeth’s Efforts

Wyeth's research efforts in Alzheimer's began in earnest in the year 2000, when a group of our scientists came to me with a proposal. They wanted to enter into collaboration with another, much smaller company to advance a new technology against Alzheimer's. The team members told me that this was, in their opinion, the single best approach to creating a really effective treatment for this disease and that they thought it had the highest chance of success of anything in development. I, of course, had to ask a few questions.

First, why were they so enthusiastic, and why did they think we had any chance of success in a disease that had proven so elusive? They explained that this technology was aimed at quickly ridding the brain of the beta-amyloid plaque that was — and still is — thought to be an important causal factor in Alzheimer's and that the work done so far on this principle in animal studies had produced the most dramatic results ever seen in these types of tests. So, second, I asked them how long it would take before we would have any real idea about whether or not this would be useful in people because we all know that animal work, particularly in diseases involving the brain, is not very predictive. They told me that they expected it would take about three or so years of research effort before they would know whether the project could move into full-scale development. Then I asked them a critical question: How much would we have to spend over those years to get even a preliminary appraisal of efficacy? After a little hemming and hawing, they told me they thought it could cost up to $100 million to do those studies.

Then I asked the really hard question: If we invested that much money over the next three years, what was the probability that when we were done with that work the answer would be "yes" — that we would have sufficient preliminary evidence about the drug’s safety and efficacy to move into the larger-scale research studies necessary for approval. This brought a lot more hemming and hawing and a little shuffling about until someone said, "There’s maybe a 30 percent probability of success," — to which I responded, "Really!" Then someone said, "Well, maybe it's more like 10 percent." When I challenged that, the real answer came out — which was that the odds of success were so low that no one could say what they were. In the end, we made the decision to go ahead — our scientists were so passionate that if I had turned them down, I would have had a mutiny.

Wyeth created a partnership with the Irish company, Elan Corporation. It was an unprecedented effort in that, for the first time, we brought together scientists from Wyeth's three research divisions. We asked leaders from our central nervous system drug discovery and development units to work in day-to-day collaboration with some of our leading biotechnology specialists and experts from our vaccine research effort.

The problem-solving abilities of these scientists, together with those of our partner, have brought to this project the unusually broad array of scientific tools and creativity that have kept us going. More than five years have gone by since we made our decision, and about all I can say after years of effort is that the program still has the tantalizing possibility of success. The development of our initial research program was stopped when we saw some early signs of a safety issue in a few patients. But we’ve come back with revised approaches, and the two leading candidates today are an antibody and a vaccine, both of which are proceeding through clinical development.

And, by the way, that $100 million estimate has long ago been spent — in fact, our partnership has invested well over twice that. Either of these programs has the potential to be the kind of new tool we need to treat or even prevent Alzheimer's disease — if we get really lucky. But risks are high, and, in the current environment, even if things go perfectly — which they rarely do — we still are looking at potential approval toward the end of this decade. I can tell you with complete candor that if this were a program in virtually any other disease, it would have been terminated years ago.

But the power of this disease and the challenge of conquering it drive us on. Wyeth is not alone on this path in trying to find a solution for Alzheimer's; there are other companies at work, as well as scientists in academia and research institutes who are making their own contributions.

Contributions of Industry and Public-Private Partnership

The scientific, pharmaceutical and research communities have been seeking to identify and develop new therapeutic targets that could dramatically alter the treatment for Alzheimer’s. There are a lot of people on this path, and a few dozen programs each have the potential to fundamentally transform the treatment of this disease.

In addition to the identification and development of promising drug candidates, there are significant research efforts into better diagnostic and screening tools. Surrogate endpoints and biomarkers have the potential to dramatically alter how we identify patients — and potential patients — and measure their clinical outcomes over time.

An example is the Alzheimer’s Disease Neuroimaging Initiative, or ADNI, a five-year public-private partnership. It brings together industry, academia and the National Institutes of Health to validate biomarkers and develop neuroimaging tools. This broad-based effort has the potential to dramatically alter how we predict the onset — and monitor the progression — of Alzheimer’s. Diagnosis and monitoring are essential to any effort to study and eventually control this disease.

Next Step: a Coordinated National Approach to AD

So why, given all the attention across various stakeholders, does the war against Alzheimer’s disease continue to progress so slowly? There are a number of significant challenges facing Alzheimer’s drug development. Among them:

• Challenges related to the design and implementation of clinical trial protocols
• The lack of urgency about the disease at a national level
• The lack of scientific consensus about what it means to “modify” the course of the disease rather than merely treat its symptoms
  

The problem is that multiple parties have an interest in resolving these challenges, but none can be addressed by any one of them alone. That brings me to what I consider a great challenge facing Alzheimer’s: the lack of a coherent strategy to respond to this disease. Unlike my examples of AIDS and avian flu, there is no global or even national focus on Alzheimer’s. Scientific work and drug development go on but at too slow a pace. Public health agencies are perhaps understandably engaged in dealing with the current devastation of the disease as much as working toward its cure. And regulatory agencies sometimes deal with Alzheimer's in the cautious way they do diseases where major therapeutic options already exist. On the regulatory front alone, worldwide cooperation between reviewers and researchers could significantly improve the probability that we will succeed and reduce development times by years.

Although there are reasons for hope — our better understanding of the disease and its progression, better diagnostic tools and some modestly useful therapies available today — the reality is that our efforts against Alzheimer's are moving at a pace that is in no way commensurate with the problem we're trying to solve.

What we need is a sense of urgency analogous to that which arose around AIDS. In the war against AIDS, government, regulatory agencies, scientists in industry and academia, and patient groups worked hand in hand to develop new therapies and to evaluate them as rapidly as possible. The results were remarkable. AIDS was first identified around 1980, and, just six years later, there was a breakthrough medication that helped people manage the symptoms. And, today, there are a number of therapies that, when used in combination, allow people with HIV/AIDS to live much longer than anyone would have dreamed possible in the early 1980s. The war has not been won, but we have made significant progress — progress that is lacking on the Alzheimer’s front.

Harnessing Science — Responding to the AD Epidemic

Knowing all of this, how do we convince the world that Alzheimer's is the next epidemic? Public awareness of the disease is high — so are assumptions and misconceptions. Unlike avian flu, which has popped up in the public eye over a relatively short period of time, a disease like Alzheimer's has been known for generations. Too many people still believe that "it's a natural process" or "it's just a part of growing old" or "there's nothing much that can be done."

We've all known someone — a parent, an aunt, a friend — who has fallen prey to this disease. A recent Gallup Poll found that nearly 50 percent of respondents worry about developing Alzheimer's. However, instead of spurring people into action, this knowledge seems to engender in some a sense of resignation, of inevitability.

What we lack is a worldwide clamor for immediate action and a solution. We need to generate a sense of urgency because, even with the best of luck, the answers won't come overnight. But we need this answer now. Those of you in this room are invaluable to this effort: We need your leadership, your voice, your passion.

The efforts of scientists across the globe are essential to developing a response to the Alzheimer’s epidemic — but they are not enough. What we also need is a sense of urgency driving a coordinated response to this disease. Scientists in academia, government and industry must work hand in hand with regulators, health care providers, and patients and caregivers. We need the kind of bold, innovative effort that has been generated in the past. The AIDS story is instructive and inspirational. If we approach Alzheimer’s with the same fervor, we will be able to harness the potential of scientific advances and truly alter the course of this epidemic.

We at Wyeth are doing our part. Wyeth has been researching innovative treatments for Alzheimer’s for more than 15 years now. We have more than two dozen projects in our pipeline, ranging from very early development through later-stage clinical trials. Our projects use all of our available technology platforms — drugs, biotech and vaccines — because we want to explore every option available to us. And I’ve already mentioned our financial commitment. Wyeth is fully committed to Alzheimer’s, and we will continue to do our part to try to harness scientific advances to overcome Alzheimer’s disease and improve the lives of patients and families.

Thank you.