The Food and Drug Administration, the government agency that approves new drugs for sale in the United States, is proposing to loosen the rules for testing new treatments for Alzheimer’s. The new rules would make it easier for new drugs to come on the market for those in the earliest stages of the disease, when symptoms like memory loss and personality changes are not prominent.
In order for a drug to become available, it must first meet stringent FDA testing requirements. Currently, the FDA requires that new drugs for Alzheimer’s must improve memory and thinking skills in affected persons. Patients who take the drug, for example, must be shown to score better on memory tests – or show a less steep decline - over time than those who take a placebo. In addition, the drugs should also lead to improvements in patients’ day-to-day functioning, such as the ability to get dressed, eat, bathe or live independently.
The new rules would be less stringent, so that drug makers would only have to show that their medications produce subtle improvements in memory and reasoning skills before being approved. Improvements in day-to-day functioning tests would no longer be required. The proposed rules were published in the New England Journal of Medicine.
The new rules would be particularly useful for testing effectiveness in the very early stages of Alzheimer’s disease, because people with very mild disease often have few symptoms and do not show marked problems in day-to-day functioning. Subtle problems with cognition, on the other hand, appear much earlier in the disease’s course and are measured through subtle psychological and mental tests.
Drug companies would still need to do follow-up studies on any drugs once they have been approved in order to confirm that they are safe and effective. So people taking a new drug would need to be monitored for adverse reactions, as well as to see if the drug is helping them. But traditionally, drug companies have not been as stringent in doing follow-up testing once a drug is one the market.
The new rules, if approved, would likely increase testing of people who are at high risk of Alzheimer’s disease but who show only very mild or no symptoms. Increasingly, doctors believe that Alzheimer’s treatment may be most effective in the earliest stages of the disease, before damage to the brain becomes widespread, and that drugs may be most useful at these early stages.
Doctors are also investigating ways to test biological markers for early disease, such as the buildup of plaque in the brain, a hallmark of Alzheimer’s, or protein levels in the spinal fluid, combined with specialized brain scans. But early markers of Alzheimer’s remain uncertain, and there is no clear diagnostic test to determine if someone is in the earliest stages of the disease.
Source: Nicholas Kozauer, M.D., and Russell Katz, M.D. Regulatory Innovation and Drug Development for Early-Stage Alzheimer's Disease. New England Journal of Medicine, March 13, 2013