FDA may fast track therapies for early Alzheimer’s

The FDA may soon clear a path for promising drug treatments for patients showing signs of Alzheimer’s disease in order to foster development and commercial availability and fill the void for this as yet untreatable disease, according to an article in the March issue of the New England Journal of Medicine.

In this perspective on the progress of Alzheimer’s therapies, most notably those pertaining to single biomarkers in the brain such as anti-amyloid therapies, Nicholas Kozauer, MD, and Russell Katz, MD, from the FDA Center for Drug Evaluation and Research’s Division of Neurology Products, expressed disappointment in recent failures and future recommendations for Alzheimer’s disease study design and subsequent FDA approval.

Drug development as a result of phase III clinical trials for Alzheimer’s treatments has not gained traction with the FDA due in part to staging of studies and initial expectations for cognitive as well as functional improvement in subjects. These criteria were applied not only for patients already suffering from extensive neurological damage, but also patients who would best stand to benefit—those in beginning stages of the disease. The FDA has been reviewing this protocol and could soon ease regulations specifically for this patient population.

“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,” noted Kozauer and Katz.

Investigational drug interventions are increasingly focusing on Alzheimer’s patients who have not yet been lost to full-on dementia and chronic neurodegeneration. Until now, new treatments could not have been made available for these patients based on cognitive measurements alone, but an FDA fast track may be opening up for drugs that show significant predictive value if approval is followed up with research documenting improvements.

“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,” explained the authors. “The accelerated-approval mechanism allows drugs that address an unmet medical need to be approved on the basis of a surrogate end point or an intermediate clinical end point (e.g., a sensitive cognitive measure), with the stipulation that postapproval studies will be conducted to verify the clinical benefit.”

Ongoing biomarker research should tease out the impact of drugs that target not only beta-amyloid peptide aggregates in the brain, as imaged by PET, but also beta-amyloid and tau proteins in cerebrospinal fluid.

“It remains possible that an effect of an intervention on one or more biomarkers could someday be accepted as predictive of a clinical benefit, but further research will clearly be needed before the effect of an intervention on a single biomarker alone could be considered an adequate surrogate measure for the purposes of accelerated approval of a candidate drug for early Alzheimer’s disease,” the authors wrote.