The FDA has issued a draft guidance designed to assist pharmaceutical companies in developing new drugs for patients who are in the early stages of Alzheimer’s disease. The proposed recommendations address patient selection and end points for clinical trials, as well as the manner in which disease modification may be demonstrated.
“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,” said Russell Katz, MD, Director of the Division of Neurology Products at the FDA’s Center for Drug Evaluation and Research in Silver Spring, Maryland.
One theory for why previous Alzheimer’s disease drugs have failed is that they were tested too late in the disease process, noted Nicholas A. Kozauer, MD, Acting Clinical Team Lead at the FDA’s Division of Neurology Products. “If the treatment is earlier, the patient may have more benefit from it,” he said.
The research group did not endorse a particular set of diagnostic criteria for early-stage Alzheimer’s disease, and instead emphasized the importance of identifying the correct patients for trial enrollment. The group also noted that many assessment tools used to measure functional or global impairment in patients with dementia have not been validated in early-stage patients. Therefore, “we consider the use of a composite scale, validated in early-stage patients to assess both cognition and function as a single primary efficacy outcome measure, to be appropriate,” stated the authors.
Regarding biomarkers, the committee noted that until there is widespread agreement that an effect on a particular biomarker is reasonably likely to predict clinical benefit, it would not consider an approval based on use of a biomarker as a surrogate outcome measure in any stage of Alzheimer’s disease.
“We are open to considering the argument that a positive biomarker result (generally included as a secondary outcome measure in a trial) in combination with a positive finding on a primary clinical outcome measure may support a claim of disease modification in Alzheimer’s disease,” stated the committee.
The recommendations were open for a public comment period, which ended on April 9.
—Colby Stong
Editor
Suggested Reading
FDA. Guidance for industry—Alzheimer’s disease: developing drugs for the treatment of early stage disease. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM338287.pdf