Draft Guidance Says Asymptomatic People Should Be Included in Alzheimer’s Trials
Drugs for cognitively and functionally normal people who have the pathophysiologic changes of Alzheimer’s disease (AD) could be approved on a single biomarker outcome, according to the FDA’s new draft guidance on drug development for early AD.
These people, defined in the draft as patients with Stage 1 disease, are an important population for Alzheimer’s clinical trials because early intervention might alter disease progression, the draft says.
“Because it is highly desirable to intervene as early as possible in AD, it follows that patients with characteristic pathophysiologic changes of AD but no subjective complaint, functional impairment, or detectable abnormalities on sensitive neuropsychological measures” (Stage 1 AD patients) are an important target population for enrollment in clinical trials, the guidance says.
But the guidance also notes that it’s impossible to measure neuropsychiatric symptoms in an asymptomatic group, so it codifies for the first time that biomarker changes alone can be enough to support an accelerated approval for an Alzheimer’s drug – including one for people with no clinical symptoms.
“Because there is no clinical impairment to assess,” the guidance also explains that a clinically meaningful benefit cannot be measured in these patients. “In Stage 1 patients, an effect on the characteristic pathophysiologic changes of AD, as demonstrated by an effect on various biomarkers, may be measured. Such an effect, analyzed as a primary efficacy measure, may, in principle, serve as the basis for an accelerated approval.”
The guidance suggests a future in which Alzheimer’s is defined by biomarkers rather than clinical symptoms, according to Lon Schneider, director of the State of California Alzheimer’s Disease Center at the University of California, Los Angeles, a perspective that comes on the heels of a similar push for a biological definition from the Alzheimer’s Association.
“This continues the 2018 FDA draft guidelines and the recent Alzheimer’s Association Criteria by saying Alzheimer’s disease equals a positive amyloid-PET scan,” said Schneider. “Effectively, it means that if a treatment changes the amyloid or tau biomarkers toward normal, that the treatment will be approved. Symptoms and function really don’t matter.”
Comments on the draft will be accepted until May 3.
Read the draft guidance here.
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