Cures Welcome at FDA
Few conditions are as wrenching as the destruction of memory known as Alzheimer’s, and few diseases have so eluded drug companies and researchers looking for a cure. So it’s welcome news that the Food and Drug Administration is inviting more innovation, and more broadly revamping the agency’s review process.
FDA recently updated its scientific thinking on early Alzheimer’s, along with other neurological conditions, and this matters because such draft guidance informs industry and academic efforts. One reality of Alzheimer’s is that the disease may “progress invisibly for years,” as Commissioner Scott Gottlieb said in the announcement, and by the time clinical symptoms arrive a patient may have lost significant function.
One important change is that FDA says it’s open to considering a novel drug for early stages that can affect cognition, or measures of a person’s thinking or memory. FDA previously said a drug had to deliver on two endpoints: cognition and function, and the latter involves an ability to perform tasks. FDA’s guidance also includes a discussion on biomarkers, which are measurable substances that offer clues to the presence or progress of a disease.
One response has been to fret that FDA is lowering standards, but cognition is a meaningful and important measure. And Alzheimer’s merits the maximum regulatory flexibility, which Congress has asked FDA to exercise. The failure rate for drugs is north of 99%, and the question is if even one therapy that delays the disease can reach the market before 2025.
The Cleveland Clinic noted in a report last year that an agent would have to be in the second of three FDA trial phases to be approved by 2025. That’s because an Alzheimer’s drug takes on average 13 years to move from laboratory to FDA review—and then another 10 years to slog through three phases of FDA trials. The current clinical trials will require more than 50,000 participants.
The larger picture is that the disease’s underlying causes are still not well understood, and the prevailing theory—stopping the buildup of proteins that form plaques in the brain—has not panned out in a clinical trial. The silver lining is that Alzheimer’s carries one of the biggest risk-reward profiles in medicine for private innovation.
Drug-approval debates tend to understate the potential of incremental improvements in therapies. One vogue complaint on the left is that expensive cancer treatments yield only modest improvements in some patients. Yet this radically misrepresents the costs and benefits of drug discovery. The Alzheimer’s Association has estimated that a drug that could merely delay the onset of the disease for five years would save Medicare nearly $350 billion over 10 years, with billions more in savings for other payers and patients.
The Alzheimer’s news came as part of a larger plan to modernize FDA’s culture of review, and the agency said it would move toward a more “team-based” approach that, say, includes a statistical expert earlier in the process. FDA evaluates drugs based on departments such as neurology or cardiovascular, yet some of the biggest challenges aren’t about organs but how to interpret data.
The real test of this guidance will come when FDA is confronted with data on a drug that requires the agency to take a risk, and that might be years off. FDA papers don’t attract as much attention as the outrage of the day on Twitter . Yet one of the most consequential results of the Trump Administration could be a drug-approval process that may be ready to act quickly and competently when a breakthrough for Alzheimer’s arrives.