FDA proposes looser rules for evaluating new drugs to fight Alzheimer's disease

In the continuing search for the fountain of youth, the U.S. Food and Drug Administration is proposing to loosen the rules for approving drugs to fight Alzheimer's disease.

In February, the FDA issued new draft guidelines that the agency posted on its web site and in the federal register, while encouraging comment. The paper is entitled, "Guidance for Industry Alzheimer’s Disease: Developing Drugs for the Treatment of Early Stage Disease," and a link is here.

An article posted Wednesday evening on the New England Journal of Medicine (link) further explained the agency's willingness to change the rules regarding how and when drug companies must measure cognition and function. Generally, the standards for clinical testing are safety and efficacy.

In the NEJM paper, doctors Nicholas Kozauer and Russell Katz wrote that, "In reviewing new-drug applications for the treatment of Alzheimer's disease, the Food and Drug Administration (FDA) has maintained that claims of improved cognition should be accompanied by evidence of improvement in function. However, 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. 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. In view of the devastating effects of this disease on patients and their families, along with its growing prevalence, innovative approaches to trial design and end-point selection are urgently needed, especially as the drug-development community turns its sights on early stages of the disease."

The doctors note that researchers have had success in identifying signs of Alzheimer's in the brain, mainly the presence of plaque.

"On the negative side, drug discovery has been disappointing," the doctors wrote. "Despite all best efforts to translate mechanistic insights concerning Alzheimer's disease into new drug products, several candidate agents have failed to demonstrate efficacy in large, well-designed, phase 3 clinical trials of late-stage disease."

One sticking point in the new guidelines will be a requirement for follow-up trials (post-marketing trials in FDA parlance) to make sure the drugs actually work and are safe. Drug companies are notoriously bad about doing such trials because there is no incentive. Once a drug is on the market and generating cash, no company wants to spend money to discover reason for pulling the drug off the market.

Katz is the director of division of neurology products in the FDA's office of drug evaluation. Kozauer, who is a medical officer in the same division, graduated from The College of New Jersey in Ewing and earned his medical degree from The New Jersey Medical School, which is part of UMDNJ.