Should the FDA Lower the Bar for New Alzheimer's Drugs?

The FDA is proposing to lower the bar for drugmakers seeking approval of new treatments for Alzheimer's disease as drugmakers have been unable to gain approval for new therapies even as incidence of the disease continues to rise.

This article published with permission from The Burrill Report.

The U.S. Food and Drug Administration is proposing to lower the bar for drugmakers seeking approval of new treatments for Alzheimer’s disease. While incidence of the disease continues to rise along with the aging of the global population, drugmakers have been unable to gain approval for new therapies.

Until now, the FDA has required drugmakers to show that their treatments improve both cognition and function in order to gain regulatory approval for use. However, this bar has been almost impossible to attain. The FDA has approved only three drugs to treat the disease since 1998, while more than one hundred have failed in clinical trials, according to a PhRMA report published in September 2012.

With the focus of drug development shifting toward preventing the onset of disease or slowing its progression in the earliest stages, and few tools that can measure functional improvements before the onset of full blown dementia, the FDA is proposing to approve new medicines that can show improvements in cognition — memory and reasoning — without also having to show improvements in patients’ abilities to accomplish the daily tasks of life.

“The premise that effective cognitive improvement will be manifested in the functional assessment of patients is untenable in the case of early-stage Alzheimer’s disease, which is increasingly the target of drug-development efforts,” write Nicholas Kozauer and Russell Katz, both members of the FDA’s Division of Neurology Products in its Center for Drug Evaluation and Research. Their comments were featured in a perspective published in The New England Journal of Medicine. “We simply do not yet have drug-development tools that are validated to provide measures of function in patients with Alzheimer’s disease before the onset of overt dementia. Improvement in function, moreover, could lag substantially behind cognitive improvement mediated by pharmacologic agents early in the course of the disease.”

The pharmaceutical industry welcomed the FDA’s reasoning, which could make it easier to get new Alzheimer’s therapies into the hands of patients.

“This is a really huge advance,” Eric Siermers, senior medical director for the Alzheimer’s disease team at Eli Lilly told The New York Times. “Kudos to the FDA.”

Lilly’s late-stage drug solanezumab had failed to meet the endpoint in a late-stage trial in patients with moderate to severe Alzheimer’s but seemed to show some promise for people with milder dementia. In January 2013, Lilly decided to test the drug in a federally funded study to see if it could prevent the onset of Alzheimer’s in older people at high risk for developing it.

In February 2013, the FDA, seeing the need for new approaches to trial design and end-point selection, issued new draft guidance for drugmakers wishing to enroll patients in the early stages of Alzheimer’s disease.

Kozauer and Katz write that “for patients whose disease is at an even earlier clinical stage, so that functional impairment would be more difficult to assess, it might be feasible to approve a drug through the FDA’s accelerated approval pathway on the basis of assessment of cognitive outcome alone,” with the stipulation that the drugmaker conduct post-approval studies to verify its clinical benefit.

“Such a regulatory process may hold promise for facilitating the approval of treatments that appear to be effective in early Alzheimer’s disease, when patients might be expected to derive the greatest benefit,” they wrote.

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