Here’s the FDA Press Release:
https://www.fda.gov/drugs/news-events-human-drugs/fdas-decision-approve-new-treatment-alzheimers-disease
“At the end of the day, we followed our usual course of action when making regulatory decisions in situations where the data are not straightforward….In determining that the application met the requirements for Accelerated Approval, the Agency concluded that the benefits of Aduhelm for patients with Alzheimer’s disease outweighed the risks of the therapy.” [Aduhelm is the trade name for aducanumab]
There is some jargon: “Accelerated Approval” is an FDA category that allows the company to market and sell a drug without full approval; i.e. there are reservations about how well it really works as a therapy. The company is usually tasked with collecting more data for the FDA to examine.
A “surrogate endpoint…is not itself a measure of clinical benefit…Drug companies are still required to conduct studies to confirm the anticipated clinical benefit. These studies are known as phase 4 confirmatory trials….If the confirmatory trial does not show that the drug provides clinical benefit, FDA has regulatory procedures in place that could lead to removing the drug from the market.” [from Accelerated Approval webpage, FDA, linked above].
So, while not “proof” that something really works, a surrogate endpoint is used for practical reasons, and it might be close enough. Aducanumab did seem to clear away a portion of amyloid plaques seen on PET scan, but other earlier monoclonals and BACE inhibitors did too, with no clinical benefits demonstrated. The FDA press release: “This reduction in plaques is reasonably likely to result in clinical benefit.” [seems like they drew a conditional conclusion?!]
The med will be expensive (see below) and it does have known side effects, but we will have to await the FDA “package insert” for more details. One is ARIA, Amyloid Related Imaging Abnormalities, that can sometimes show brain swelling, bleeding, and some suggest shrinkage. Of course, chemo agents are expensive and create sometimes life-threatening side-effects.
A number of cancer drugs get accelerated approval (Avastin, a monoclonal antibody, for breast cancer) only to have the FDA later pull its approval. However, sometimes it takes awhile for the FDA to evaluate data. Avastin for glioblastoma, an aggressive brain tumor, took eight years for full approval, FDA concluding that it gives brain cancer patients ~3 more months to live, only in combination with another agent, with no comment on quality of life.
Here’s a STATnews piece on the aducanumab decision:
FDA grants historic approval to Alzheimer’s drug designed to slow cognitive decline
Washington Post story also points out some controversy.
https://www.washingtonpost.com/health/2021/06/07/fda-approves-alzheimers-drug-aducanumab/
Advocacy groups like Us Against Alzheimers and the Alzheimer’s Association have pushed for approval, saying the drug may give patients “more time.” Let’s hope it’s quality time. The drug company certainly now has more time, and can offset its confirmatory trials and previous research and investment costs with sales.
What kind of drug do families want, anyway? Alzheimer Gadfly, who used to prescribe chemo with accelerated approval, once described the perfect drug for kids: “..the ideal therapy: curative in a single dose, this concoction could be mixed with a spoonful of chocolate syrup, and—of course—not cause any side effects…” So let’s hope this one does work in its confirmatory trials, has manageable side effects, and paves the way for more effective, less toxic agents in the near future! Will there be combo trials (with reduced dose BACE or cognitive enhancing agents) in the future?
