Alzheimer’s experts call for changes in FDA drug approval standards

Leading Alzheimer’s disease researchers and a prominent patient advocate today published an analysis, Single Endpoint for New Drug Approvals for Alzheimer’s Disease, urging the Food and Drug Administration (FDA) to clarify and modernise its current approach for approving new treatments for Alzheimer’s disease.

The analysis, authored by George Vradenburg, UsAgainstAlzheimer’s Co-Founder and Chairman, and Drs. Howard Fillit, Dave Morgan, Marwan Sabbagh, Paul Aisen and Richard Mohs, recommends that the FDA approve new medicines that demonstrate a proven benefit on at least one therapeutic endpoint – either cognition or function.

Endpoint discussion

The current FDA standards require a new drug to show benefits on both proven endpoints, an unnecessarily challenging hurdle the authors say may be inhibiting investment in new Alzheimer’s treatments.

The authors are members of ResearchersAgainstAlzheimer’s (RA2), an UsAgainstAlzheimer’s global network of more than 450 disease researchers.*

"If the FDA were to state that meaningful efficacy on a single endpoint is sufficient for approval, we believe that it would impact prospective investments in this therapeutic area as well as clinical-trial design," wrote the authors.

"We believe a clarified and modernised FDA approval standard for Alzheimer’s disease would catalyse renewed investment in the discovery and development of new medical advances for Alzheimer’s disease, particularly in early-stage companies and for venture investment."

The analysis points out that Alzheimer’s disease biopharmaceutical research is lagging well behind that of other diseases, despite the fact that Alzheimer’s diagnoses will triple in future decades and that there is no current means to prevent, treat or cure the disease. The analysis notes that in 2014-2015, there were only 135 ongoing interventional Alzheimer’s disease clinical trials compared to nearly 5,000 similar trials for oncology drugs.

Updating approval process

The authors wrote that a modernised FDA standard for Alzheimer’s medications would reflect changes in the field and in treatment since the 1990s, and it would also align with draft guidance issued in 2013 for drug development for early Alzheimer’s.

Specifically for Alzheimer’s, the authors argue, if a new drug improves memory but has less positive impact on a patient’s daily functioning skills, the medication should still meet standards for FDA approval, because clinically meaningful improvements in cognition matter importantly to persons with Alzheimer’s independent of functional improvement and vice-versa.

"Irrespective of the degree of impact on secondary measures, the notion that the FDA would deny approval for a safe and well-tolerated drug candidate that achieves its primary endpoint of improving cognition in patients with Alzheimer’s disease is almost unthinkable," the authors wrote.

The authors emphasised that the new standard is essential at a time in which recent clinical trial failures on Alzheimer’s drugs have adversely affected investment in disease research.

The FDA has not approved a novel Alzheimer’s treatment since 2003, and the 5.5 million Americans with Alzheimer’s and their caregivers are desperate for innovation.