Why Do So Many Alzheimer’s Drugs Fail in Clinical Trials?

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Semagacestat, tramiprosate, tarenflurbil, latrepirdine: These names may not mean a lot to you, but all four of them were high-profile would-be Alzheimer’s drugs that — in the last two to three years — have failed the last phase of clinical trials. They made it through the safety stages okay. They just didn’t work well enough; they didn’t help enough patients.

What’s going on, and why so many failures? In a brief editorial this week in the Lancet, the editors of that venerable medical journal offer some possible answers:

Current treatment targets patients with symptomatic Alzheimer’s disease. But perhaps the disease is being treated too late, when damage is irreparable? The best time to treat Alzheimer’s disease is likely to be before memory loss and tissue destruction occurs, but this is hard to model in animals.

And animal models, of course, are generally what we use to understand the molecular basics of disease formation — particularly for a disease like Alzheimer’s. No one would sign up for an experiment they thought could induce Alzheimer’s symptoms, after all, even if it were possible to get such a study past a research ethics board (which it wouldn’t be). The editors continue:

Drug-industry scientists are failing themselves if their animal studies are poorly done or use the wrong model, and their companies are failing academics who do their phase 3 trials with them, trial participants, and shareholders.

Drug design, once again, is proving to be a very tricky business.