Politics and a hunt for profits at play as FDA experts gear up to review Biogen’s aducanumab

Politics and a hunt for profits at play as FDA experts gear up to review Biogen’s aducanumab

There has been much navel-gazing over Biogen’s Alzheimer’s disease hopeful aducanumab, with some analysts seeing approval on the cards and many others adamant that not only should it be rejected, but it should in fact not be approved on both moral and scientific grounds.

Here’s the history: The data underpinning the FDA filing, which the advisory committee Friday will focus on, come from two phase 3 studies dubbed EMERGE (aka study 301) and ENGAGE that tested aducanumab in patients with early-stage and mild Alzheimer’s, as well as from a phase 1b study.

There was a discrepancy between the phase 3 studies—patients in the EMERGE trial (aka study 302) who got the highest dose of aducanumab had a statistically significant improvement on a clinical dementia scale, but the same patient group in the ENGAGE study did worse than patients taking placebo on that same measure as well as on a test of cognitive function.

What’s more, the phase 3 program flunked a futility analysis in March 2019, leading Biogen to pull the plug on the studies, but the company about-faced eight months later, saying the analysis was “incorrect.”

Biogen argued the futility analysis was based on a smaller data set that featured fewer patients who received high-dose aducanumab. Adding in the additional data showed aducanumab reduced clinical decline, the company said at the time, and then decided to file. It has little to lose in trying, and its attempt comes after several years of R&D setbacks and mounting pressure on its key franchises.

Yesterday, the FDA released its briefing documents ahead of tomorrow’s AdComm, which essentially all but agreed on Biogen on the above points and said the drug appeared in the main safe and efficacious.

While the AdComm is yet to meet, and a decision from the FDA isn’t expected until next year, an approval now seems much more likely than it did at the start of the week.

The data are weak. There’s a negative study, and one positive, though the positives needed to be dug out. Biogen will try and make it look as good as possible, but,in the end, this is not a curative therapy. It may help a subset of patients, at best.

As a society, we desperately need new drugs for Alzheimer’s, still one of the leading causes of death in the Western world. Having watched both of my maternal grandparents decline and die of the disease over the past three years, I can attest to the need for better intervention than a care home.

There are several drugs on the market for the disease, but they do little in the long run, and the main thrust of research over the years, which includes the beta amyloid thesis behind Biogen’s drug, has failed time and again.

Many see this as a time to move on, but an FDA approval, and resounding positivity from the docs, could be seen as resurrecting moribund research. This was shown when shares in companies like Lilly, which has worked on similar R&D, jumped simply on the release of these documents.

In a note to clients, Evercore analysts pulled no punches, saying that while they now expect approval, “FDA politics [were] at full display in alzh AdCom documents,” because the agency needs to start bringing through new drugs for the disease. You want the FDA to follow the science, not the politics.

Evercore also pointed out that, while broadly very positive, the documents did see an outlier: “There is a statistician’s review – which is NOT consistent the main reviewer’s key conclusions … key line: ‘it’s not like we have one strong study in isolation … if you have two (studies) and you take the best and pretend like it’s the only one, your estimate is likely biased.’”

The AdComm will need to discuss this, so it will not be smooth sailing for Biogen. But it will need this win. It could see $5 billion and up to $10 billion in peak sales from the drug, and this will be needed to shore up future losses from its multiple sclerosis pipeline and generic pressures.

There’s an extra wrinkle here, too: The FDA won’t make a decision until next year. If there is a Joe Biden White House, a new president can decide to fire FDA Commissioner Stephen Hahn, M.D., and bring in his own nominee. That, too, could change aducanumab’s fate if a new commish wanted to make the FDA firmer on these sorts of decisions.

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