- The Food and Drug Administration issued five new guidance documents this week designed to support the clinical development of drugs for Alzheimer's disease and other neurological conditions that have seen relatively fewer therapeutic advances.
- Notably, the FDA indicated efficacy on trial endpoints measured by biomarkers could be sufficient to win accelerated approval in very early Alzheimer's disease where there are few, if any, symptoms of impairment.
- Still, the FDA noted the lack of consensus around which biomarkers should be used to assess treatment effect in early Alzheimer's disease. Other recommendations include establishing better and clearer clinical endpoints for early disease, and ensuring suitable duration for studies.
The draft guidance on Alzheimer's, which updated previous guidance issued in 2013, establishes the FDA's current thinking around enrollment criteria and selection of endpoints in clinical trials of patients with early disease.
These patients are particularly challenging to test drug candidates in, due to the lack of cognitive and physical symptoms even as the pathophysiologic changes characteristic of Alzheimer's first begin to occur.
Drugmakers have zeroed in on this group, however, because of researchers' belief that halting damage at this stage is critical to prevent later declines.
"This document describes innovative approaches to studying very early disease before the onset of dementia, including strategies for trials incorporating patients with Alzheimer's who haven't experienced any visible impairment … but who may be identified through the use of sensitive cognitive screening, imaging tests, or biomarkers," wrote FDA Commissioner Scott Gottlieb in a Feb. 15 statement.
A handful of drugs are approved to ease the symptoms of Alzheimer's, but none are disease modifying. The drug industry's efforts on that front have so far turned up only an ever-lengthening list of clinical setbacks and frustrations.
By issuing draft guidance on Alzheimer's, the FDA is both signaling its flexibility and pushing drugmakers to keep up drug development efforts.
Such a boost may be needed after a recent slate of disappointments.
Merck & Co. announced this week it had discontinued a Phase 3 study of verubecestat in very early stage Alzheimer's disease, one year on from the company halting the EPOCH Phase 3 trial after an independent committee's reported there was "virtually no chance of finding a positive clinical effect."
Earlier this month, Boehringer Ingelheim International GmbH announced that it was shutting down development of BI 409306 after missing endpoints in Phase 2.
While both drugs were not widely expected to succeed, the failures follow trial misses for more anticipated studies of Axovant Sciences Ltd.'s long-shot hope intepirdine and Eli Lilly & Co.'s solanezumab before that.
Some ongoing studies are looking a little wobbly, too. Biogen Inc. increased enrollment into its Phase 3 studies of its all-important aducanumab following what the company described as "variability" on the primary endpoint. Company executives expressed confidence in both the study and aducanumab but, given the history of failure, any signs of shakiness are usually met with concern.