FDA Facilitates Research on Earlier Stages of Alzheimer's Disease

By Jane Farrell

AlzheimerΓÇÖs disease is a nightmare haunting many Americans.

More than 5 million Americans have been diagnosed with the disease, which is the sixth leading cause of death in the United States and the most common cause of dementia among people 60 or older. AlzheimerΓÇÖs is an irreversible, progressive brain disease that slowly destroys memory and thinking skills. It eventually robs sufferers of the ability to perform even the simplest tasks of daily life.

Despite years of intensive efforts by scientists to develop new safe and effective treatments for AlzheimerΓÇÖs, options remain limited. In the last 20 years, the federal Food and Drug Administration (FDA) has approved five drugs for the diseaseΓÇöthe most recent one in 2003. Although the drugs can provide some benefit, more needs to be done.

A recent development could bring better results. Three years ago, FDA scientists released a draft guidance that may help companies conduct clinical trials focused on what could be a more treatable stage of the disease: before the onset of noticeable dementia.

Research has shown that there is a lag of many years between the beginning of changes in a patientΓÇÖs brain and the onset of AlzheimerΓÇÖs symptoms. Yet in the past, clinical trials examined AlzheimerΓÇÖs patients when their symptoms had become clearly apparent, long after the changes in their brains had started. Some researchers have theorized that the greatest benefits will be available if a treatment can be developed for very early in the disease course, when people have the very first symptoms of AlzheimerΓÇÖsΓÇöor even earlier.

For that reason, the development of drugs for the treatment of AlzheimerΓÇÖs disease has increasingly focused on the stages before the onset of overt dementia. A 2013 FDA draft guidance responded to this development by discussing the design of clinical trials for drugs for AlzheimerΓÇÖs patients who are still in the very early stages of the disease, when only subtle symptoms are present.

ΓÇ£There may be a window of opportunity to affect the disease before people experience symptoms,ΓÇ¥ says Eric Bastings, M.D., a neurologist and the deputy director of FDAΓÇÖs Division of Neurology Products.

FDAΓÇÖs draft guidance may help researchers design clinical trials for early stage AlzheimerΓÇÖs therapies. The agency hopes that the guidance will serve as a focus for continued discussions among FDA, sponsors of new drugs, the academic community, and the public.

ΓÇ£Earlier and more precise identification of patients with early changes in the brain who will go on to develop AlzheimerΓÇÖs is important for the success of these clinical studies,ΓÇ¥ says Billy Dunn, M.D., a neurologist and the director of FDAΓÇÖs Division of Neurology Products. ΓÇ£We hope that earlier interventions, before further extensive damage to the brain sets in, will be more successful. WeΓÇÖre very excited about the potential for this research to result in safe and effective treatments for early AlzheimerΓÇÖs disease.ΓÇ¥

FDAΓÇÖs draft guidance aims to encourage research and discusses FDAΓÇÖs thinking about conducting new clinical trials at the very early stages of AlzheimerΓÇÖs diseaseΓÇöin patients with no obvious symptoms, or even no symptoms at all.

One example of how clinical trials are changing is the Anti-Amyloid Treatment in Asymptomatic AlzheimerΓÇÖs study, a landmark public-private partnership funded in part by the National Institute on Aging. Participants are people ages 65 to 85 who have normal thinking and memory function but might be at risk for developing AlzheimerΓÇÖs, based on an advanced brain scan. The three-year study is testing whether a new investigational treatment can slow the memory loss caused by AlzheimerΓÇÖs.

One of the biggest challenges is correctly identifying patients at risk for developing AlzheimerΓÇÖs. In recent years, researchers have identified biomarkers (measurements, often based on a laboratory test, of a condition or disease) that may indicate a higher risk for developing AlzheimerΓÇÖs. Some of them are gene mutations.

ΓÇ£In a small proportion of patients, having someone in the family with AlzheimerΓÇÖs dramatically raises the risk that they, too, will have the disease,ΓÇ¥ Dunn says.

For most people, however, the risk of AlzheimerΓÇÖs is not quite as readily identified.

ΓÇ£If we can use biomarkers to better choose who should be in which clinical trials, these biomarkers hopefully will help increase the likelihood that weΓÇÖll be able to show the drug effect in clinical trials,ΓÇ¥ Bastings says.

Prompt detection of the disease may lead to the development of early treatments that could help patients retain their brain function for a long time, even if their underlying AlzheimerΓÇÖs may not be reversed.

ΓÇ£WeΓÇÖre very excited about increasing our ability to find beneficial treatments for so many people with this devastating disease,ΓÇ¥ Dunn says.

This article appears on the FDAΓÇÖs Consumer Updates page, which features the latest on all FDA-regulated products.