FDA issues draft guidance on drug development for Alzheimer’s

FDA issued a proposal designed to assist companies developing new treatments for patients in the early stages of Alzheimer’s disease, before the onset of overt dementia.

Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks of daily living. In most people with Alzheimer’s, symptoms first appear after age 60. Alzheimer’s disease is the most common cause of dementia among older people. According to the Alzheimer’s Association, Alzheimer’s is the sixth-leading cause of death in the United States and the only cause of death among the top 10 in the United States that cannot be prevented, cured, or even slowed. Payments for care are estimated to be $200 billion in the United States in 2012.

“The scientific community and the FDA believe that it is critical to identify and study patients with very early Alzheimer’s disease before there is too much irreversible injury to the brain,” Russell Katz, MD, director of the Division of Neurology Products in FDA’s Center for Drug Evaluation and Research, said in a press release. “It is in this population that most researchers believe that new drugs have the best chance of providing meaningful benefit to patients.”

The draft guidance “Guidance for Industry, Alzheimer’s Disease: Developing Drugs for the Treatment of Early Stage Disease,” explains FDA’s current thinking about the way researchers can identify and select patients with early Alzheimer’s disease, or those who are at risk of developing the disease, for participation in clinical trials. In recent years, the research community has tried to find ways to identify these patients using criteria that are based on biological indicators (biomarkers). Researchers have also tried to develop sensitive clinical measures that can detect subtle mental decline.

"Alzheimer’s disease is recognized as the most common form of dementia and with the increasing prevalence of the neurodegenerative disorder, it is vital that steps are being taken to find ways to assist with early identification and development of newer treatment options," said Formulary Advisor Abimbola Farinde, PharmD, MS, clinical staff pharmacist at Clear Lake Regional Medical Center in Webster, Texas. "The draft guidance . . . serves as another landmark movement toward achieving a better understanding of this disease, and developing effective therapeutic options that will target the disease during its initial onset and assess the effectiveness of treatments at this particular stage."

The draft guidance is meant to serve as a focus for continued discussions between the FDA and pharmaceutical sponsors, the academic community, advocacy groups, and the public, according to Dr Katz.

For drugs designed to treat patients with overt dementia, FDA currently requires that treatments not only show an effect on abnormal thinking, but also how well patients function. The goal for these trials is to ensure that any beneficial effect on thinking is associated with a clinically meaningful outcome for the patient, eg, improvement or lack of decline in how patients feel or function.

However, because patients with early Alzheimer’s disease have little-to-no impairment of global functioning, it is difficult to assess changes in function in these patients. This can make it difficult to determine if a given treatment’s effect is clinically important.

FDA is seeking public comment on the draft guidance for 60 days. Instructions on how to submit comments are included in a related Federal Register notice. In finalizing the guidance document, the agency will consider the information received from the public.