A panel of medical experts recommended strongly against approval for a new drug for Alzheimer’s disease that is up for review at the Food and Drug Administration, the Federal agency that approves novel treatments based on efficacy and safety data. The drug, aducanumab, would be the first entirely new drug specifically approved for Alzheimer’s disease in nearly two decades.
The recommendation, made at an evidence review hearing on November 6, does not mean that the FDA will not approve the drug in the coming month. The agency has until March of 2021 to either grant — or deny — approval. But the FDA often follows the nonbinding advice of its advisory committees. If they were to reject it, it might not be final; they might allow or request more data, new analysis of the results, or more clinical testing.
Unlike currently approved drugs for Alzheimer’s, which may ease symptoms for a time but do nothing to stop the relentless downward progression of disease, aducanumab works in a novel way that is meant to modify the underlying course of the disease and slow its advance. The experimental drug does not, however, cure Alzheimer’s. The actual data do not allow us to know if it could prevent the disease if it was given long before the symptoms are visible.
The drug’s maker, Biogen in collaboration with Eisai, disappointed patients last year when it stopped trials of the drug and announced that studies did not show benefits. But they revived hope after a reanalysis of the data from one of two major studies of the drug found that certain subsets of patients did appear to show benefits when the drug was given at a high dose. After 18 months, some people with early Alzheimer’s disease who were getting the drug had 15 percent to 27 percent less decline in memory and thinking skills compared to those taking a placebo. Those getting the highest doses of the drug appeared to show the most benefit.
At the seven-hour hearing, the 11 committee experts were not convinced that the evidence clearly showed benefit for those with Alzheimer’s disease. They cautioned against rushing approval of a drug that may have no benefit and called for more studies to prove that any benefits outweigh potential risks.
In the weeks preceding the hearing, some at the FDA and scientists at Biogen had spoken encouragingly of the drug’s promise. Some Alzheimer’s groups had sent letters to the advisory panel urging approval of aducanumab, citing the lack of effective treatments for Alzheimer’s, a disease that affects over 5 million Americans.
But committee members emphasized that approving a drug without rigorous scientific evidence could jeopardize future clinical research. With so much at stake in the fight for effective new therapies for Alzheimer’s disease, “we have to get it right,” said Dr. G. Caleb Alexander, professor of epidemiology and medicine at the Johns Hopkins Bloomberg School of Public Health in Baltimore.
Aducanumab is what is known as a monoclonal antibody drug and is given as a monthly infusion into the blood stream. It targets beta-amyloid, a toxic component that builds up in the brains of those with Alzheimer’s disease. Researchers had hoped that reducing the amount of beta amyloid and consequently preventing the buildup of beta-amyloid aggregates that form plaques might halt the loss of brain cells.
As with dozens of other experimental drugs, early, small-scale studies of aducanumab suggested it might have benefits in slowing cognitive decline, and it appeared to be generally safe. But early promise was often dashed in late-stage testing in large numbers of people, leading many drug manufacturers to abandon them.
The fact that Biogen revived interest in aducanumab renewed hopes for better treatments for Alzheimer’s. Evidence suggests that brain changes in Alzheimer’s typically begin many years prior to the memory loss and other symptoms that lead to a clinical diagnosis, and researchers hope that administering drugs at the earliest stages might produce the best results. It is also plausible that this treatment, as well as other drugs that have been tested and failed on large groups of patients, might only work in a sub-population of patients — a sub-population that we don’t know yet how to define.
New basic research is needed to understand what causes Alzheimer’s disease, and how it might be treated or prevented, or its progression slowed. The Fisher Center continues to study the underlying mechanisms of the disease, research that may pave the way for effective treatments.
A number of drug companies are continuing to test dozens of experimental drugs that look at various possible mechanisms for the disease, including inflammation, the immune system, various infections and a brain substance called tau. Other drugs that target beta-amyloid are also undergoing testing.
By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.
Source: Biogen, October 2020. Food and Drug Administration hearing, November 6, 2020.