STATPlus In an effort to ease drug development for Alzheimer’s disease, the Food and Drug Administration is endorsing a new approach that would rely on biomarkers to approve medicines before patients show any signs of the illness, instead of demonstrating a drug alleviates symptoms. To entice researchers, the agency would accelerate approval of a drug for people who do not indicate they have the disease if the treatment has an effect on a biomarker, according to a draft guidance released on Thursday.
The agency did not specify any biomarkers, but presumably, this could include beta amyloid or tau, which are proteins believed responsible for triggering the disease. Once a drug becomes available, a drug maker would then have to conduct additional studies to confirm its treatment offers a benefit, notably a change in cognition. This would also amount to a significant policy revision, because the FDA previously looked for treatments that could provide changes in function, as well as cognition. Although the agency acknowledged a biomarker may not “reasonably” predict an actual benefit, the effort underscores a need to loosen standards in a way that may provide further encouragement to discouraged researchers and patients.
Indeed, the move comes as drug makers have racked up a growing number of failures trying to develop a useful treatment. The list includes companies that boast some of the deepest pockets in the pharmaceutical industry. Pfizer (PFE), Eli Lilly (LLY), and, just this week, Merck (MRK), have scuttled efforts. Pfizer, in fact, recently closed its neurosciences unit altogether. Also this week, Biogen (BIIB) increased the number of patients in a closely watched trial, a move that concerns investors.
The long run of setbacks and disappointments prompted a group of researchers and patient advocates last year to argue that the FDA should evaluate Alzheimer’s drugs for efficacy in either cognition or function — but not both. By adopting this stance, the FDA could make it easier for the pharmaceutical industry to maintain investment in the notoriously difficult field, one advocate suggested.
“This really opens the door to working with industry to identify standards for approving drugs in earlier stages of the disease than in the past,” said George Vradenburg, executive director of UsAgainstAlzheimer’s, a patient advocacy group.
“It says to a drug maker, ‘If you target a drug for people at an early stage disease, we’ll assess the drug based on ability to improve cognition and you don’t have to wait to see whether the drug changes functional status.’ So it could change historic efficacy standards and align regulatory science with academic science.”
Indeed, one expert noted that trials have already been underway to explore useful biomarkers.
“The FDA recognized that the field is moving to looking at very early stages of the disease and that we are learning it’s a very long process,” said Dr. Oscar Lopez, the director of the Alzheimer Disease Research Center at the University of Pittsburgh. “Interventions have to occur even before a person becomes cognitively impaired. And we actually have a very rich and diverse pipeline (of possible drugs.) What they’re doing is putting in writing what is happening.”
[UPDATE: We should note that UsAgainstAlzheimer’s has accepted funding Eli Lilly and, according to the CMS OpenPayments database, Lopez has done consulting work for Grifols, which is developing an Alzheimer’s treating.].