The real trouble with Alzheimer’s research

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The story has become all too familiar. After an investment of approximately $1 billion, Eli Lilly announced it will not seek regulatory approval to market its drug solanezumab.

In trial after trial, Alzheimer’s drugs have a near-perfect record of failure. No major health condition can match this record. What would motivate the company to spend $1 billion on a long shot with so little potential benefit? Clearly the company had its own analysis to justify this large investment.

This analysis has a name, in fact: It’s called willingness to pay, which is critical for developing new products. For treatment of an incurable disease like Alzheimer’s, families are willing to pay a high price for small effects, even if their financial circumstances are stressed. If solanezumab had been approved, we can only estimate the cost of the drug for patients, but tens of thousands of dollars yearly is a probable ballpark. At that price, the company would recoup its billion-dollar investment many times over.

Every Alzheimer’s patient deserves dignified treatment, and even a small benefit might be a worthy goal. But think about the sacrifices when chasing drugs with small effects. Families face painful decisions: Should we buy the drug or send a child to college? For those with scarce resources, allocating precious funds toward a pharmaceutical company’s newest product means cutting something else. The financial investment made in developing these potentially lucrative drugs leaves research on more effective measures severely underfunded and delays the opportunity to make a significant dent in the disease. Each failure leaves the public demoralized and less inclined to support research, which, ultimately, is the only real solution.


After each trial failure, a chorus of voices hurls invective at one another other. Some double down on the failed trials and want to tinker with the approach. But most trials target a protein called amyloid in the brains of Alzheimer’s patients. These researchers tend to be those who have already invested their scientific credibility in the “amyloid hypothesis.” On the other side are those who say it is time to move on, that antiamyloid drugs, at least when used alone, are ineffective, and the complexity of Alzheimer’s disease means new targets and new approaches are essential.


It is a highly polarized dispute, and judging all the failed Alzheimer’s trials too harshly would be a mistake. But there are some take-home lessons from the Eli Lilly trial. At the outset of a drug trial, researchers should assess expectations for the magnitude of the effect size. Will the drug go beyond a statistically significant but minimal benefit to improve a patient’s overall welfare? We need to weigh the financial burden a treatment will impose on families and the sacrifices they will make when the benefits are small. And we need to take off the blinders as we look for a single mechanism as a cause of Alzheimer’s disease. The great disparity in our minimal knowledge of Alzheimer’s disease compared with our rich knowledge of cancer makes a stark contrast when designing treatments. The cancer field draws upon vast sectors of basic biology from which treatments are emerging; the Alzheimer’s field remains constrained by its incessant focus on a narrow view of the disease.

Dr. Kenneth S. Kosik is Harriman professor of neuroscience and codirector of the Neuroscience Research Institute at the University of California, Santa Barbara. He is the coauthor of “Outsmarting Alzheimer’s Disease” with Alisa Bowman.