The US FDA has developed new guidance on the development of medicines for Alzheimer’s as attention shifts towards intervening earlier in the course of the disease.
Disappointing late-stage trial results for a number of drugs targeting patients in whom Alzheimer’s is already taking hold – including Pfizer’s bapineuzumab and Lilly’s solanezumab just last year – have focused thinking on starting treatment before symptoms develop.
“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,” commented Russell Katz, who heads the FDA’s division of neurology products.
“It is in this population that most researchers believe that new drugs have the best chance of providing meaningful benefit to patients,” he added.
Pfizer and Lilly were both tested in patients with mild-to-moderate Alzheimer’s with a view to delaying cognitive and memory decline.
Pfizer decided to give up in its candidate – at least in intravenous formulation – when trials showed no benefit, although Lilly was sufficiently encouraged by an efficacy signal in a subpopulation of patients with mild disease to start a new trial in early-stage patients.
Meanwhile, Roche subsidiary Genentech has gone one step further with its crenezumab candidate, licensed from AC Immune, and will test the therapy in a healthy group of patients who are genetically at extremely high risk of developing Alzheimer’s.
The new guidance explains the FDA’s current thinking about the way researchers can identify and select patients with early Alzheimer’s disease, as well as those who are at risk of developing the disease, for participation in clinical trials, according to the agency.
It also provides advice and information on the selection of biomarkers, trial design and more sensitive measures of mental decline.
One challenge facing developers of Alzheimer’s drugs has been that, according to FDA criteria, new medicines have to show an impact on not only cognitive function, but also on overall patient functioning.
The agency notes that the principles behind this ‘co-primary endpoint’ approach still apply, but it recognises this may be impractical in patients who have yet to develop any overt dementia symptoms.
“Clear evidence of an effect on delaying cognitive impairment may provide sufficient evidence of effectiveness” in early-stage studies, according to the guidance.
The document is open for public comment for 60 days.