Earlier this month, the Food and Drug Administration approved aducanumab (under the brand name Aduhelm), the first new drug for the treatment of Alzheimer’s disease in nearly 20 years. Patients with Alzheimer’s have shared stories of the disease’s devastating effects, including knowing that it will alter their sense of who they are and rob them of the ability to care for themselves. We understand that an approval of this magnitude is of intense interest, so we want to explain what we have done and why we have done it.

The decision to approve this drug was based on rigorous science, with thorough evaluation of data from clinical studies.  (Absolutely untrue; the results of said studies did not manifest any proof of improvement to the lives or memories of Alzheimer’s patients.) The FDA conducted an extensive review of current and relevant scientific literature and carefully considered feedback from the advisory committee. (All of which recommended that the drug not be approved.) The evidence was complicated and, in some instances, contradictory. After reviewing the data, we concluded evidence from the trials did not, on its own, convincingly demonstrate a clinical benefit and did not meet the standard for “regular” approval.( D-uh.) That’s what we heard from the advisory committee, and we agreed.

However, as we continued our review, we concluded that the data met the standard for accelerated approval. This pathway is available under federal law when a drug intended for a serious disease is expected to provide a meaningful advantage over available treatments. (Actually, this approval process has been employed specifically for cancer treatment drugs, where it is much more difficult to run blind, broad clinical trials.)  A drug may be approved under this pathway when it is shown to improve a measure of a disease and when it is “reasonably likely” that this measure predicts clinical benefit. Note that the law says “reasonably likely” to predict, not “certain” to predict. In other words, accelerated approval was designed for situations in which there is residual uncertainty about clinical benefit. (That is why it is used for cancer therapies- it is, as I stated above, much more difficult to run controlled clinical trials for these maladies.)

Why would we accept uncertainty when approving a drug? The accelerated pathway was created to give earlier access to potentially valuable drugs for patients who have a serious disease, such as Alzheimer’s, with limited or no treatment options. These patients are often willing to accept some degree of uncertainty of clinical benefit.

While aducanumab’s trials suggested — but did not confirm — clinical benefit, they did convincingly and consistently show that the drug reduces amyloid plaque in the brain, a defining pathological characteristic of Alzheimer’s disease. (However, years of examination have not proven that reducing amyloid plaque improves the lives of Alzheimer’s patients.) Based on extensive analyses of the data from the aducanumab program, and a thorough review of publicly available information, we concluded that the reduction in amyloid plaque correlates with slowing of disease progression and is reasonably likely to predict clinical benefit.

We acknowledge there is some (this might be the understatement of the year…. including the 6th of January being a tourist visit and not an insurrection or riot.) controversy about this conclusion. One of the reasons is that in the past, some drugs directed at amyloid haven’t shown benefit. (Hmm.  Could you name ONE that did?) But unlike aducanumab, these prior drugs did not substantively lower amyloid plaque. Newer drugs that are being developed for Alzheimer’s have reported reduction in amyloid plaque with slowing of the progression of the disease.

The clinical benefit we believe to be associated with aducanumab could make a difference for patients with Alzheimer’s — for instance, by delaying the time when they may no longer recognize their loved ones or be able to dress or feed themselves. Hopefully, that means they have more time to live independent lives.

Because there is residual uncertainty about clinical benefit, the company that will market aducanumab is required to conduct a new study to verify and describe the drug’s benefit. If this study fails to verify clinical benefit or is not conducted in a timely manner, the FDA can initiate proceedings to withdraw the drug’s approval. (The time period for this second trial is a little squishy- how about narrowing it down with a specific deadline.)

Some criticisms of our approval have centered on the drug’s pricing. (Pricing is not an FDA issue.  However, the rules do stipulate that when FDA approves a drug, Medicare must cover the cost.  And, Biogen has chosen a cost that crossed the border or reasonableness by at least a factor of 3.) We understand and care that high drug prices have a direct impact on patients. However, the FDA has no legal authority to investigate or control the prices set by manufacturers, distributors and retailers.

During the past two decades, we have used accelerated approval authority extensively for drugs to treat a range of cancers. Over this time, there has been a sea change in cancer treatment — with markedly longer survival and even cures. Accelerated approval has been one of the tools we’ve used to give cancer patients earlier access to promising drugs. (Again- that is exactly why this process exists for cancer patients.)  In a high proportion of instances, we have found that subsequent studies confirmed clinical benefit. Even though not every drug worked as expected, these approvals have propelled progress forward. Alzheimer’s disease is no less serious, and no less devastating, than cancer.

Often, at the time of approval for these cancer drugs, there was limited clinical data available. By contrast, the amount of clinical data for aducanumab was extensive and included a safety database of more than 3,000 patients exposed to the drug. This strengthened confidence in our conclusion that the expected benefit of aducanumab outweighs the risks.

Before we approved aducanumab, we met with people from a variety of backgrounds living with Alzheimer’s disease, as well as with their families and caregivers. They made it clear that they wanted access to a treatment option with the potential to stop or delay their disease, and that they were willing to accept some degree of uncertainty. Our approval of aducanumab — based on thorough, expert analysis and an uncompromising adherence to scientific standards — provides that option and is consistent with our mission to bring lifesaving therapies to patients.

Patrizia Cavazzoni is director of the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration. Billy Dunn is director of CDER’S Office of Neuroscience. Peter Stein is director of CDER’S Office of New Drugs.