A preliminary autopsy of Biogen’s Aduhelm catastrophe

It was October 23, 2019, and a typical autumn morning in New York—slightly cloudy but generally pleasant, wisps of an early morning shower still glistening on the streets of Manhattan. But Biogen CEO Michel Vounatsos and former chief medical officer and R&D head Alfred Sandrock were in town on a most atypical mission: Justify the company’s shocking decision to reverse course and submit its experimental Alzheimer’s treatment Aduhelm, or aducanumab, for Food and Drug Administration (FDA) review following a futility analysis of trial data that, just seven months prior, led Biogen to toss the drug hopeful into the ever-heaping dustbin of Alzheimer’s clinical failures.

Lazarus, it seemed, was newly risen. And Sandrock and Vounatsos were eager to convince the masses (and regulators) they weren’t simply propping up a ghost, but rather singing the praises of a game-changing advance for dementia patients that was, contrary to what the murky-at-best evidence of Aduhelm’s safety and efficacy in curbing cognitive decline might suggest, the real deal. “I think aducanumab could be the first ray of hope for many other drugs to come in the space,” Sandrock told me that day in a Manhattan hotel conference room serving as Biogen’s makeshift war desk. (I still worked at Fortune Magazine back then, where I covered healthcare and biopharmaceuticals for nearly six years.)

“Today is about hope and opportunity. They see the science, the patient groups coming in,” Vounatsos declared. “We need to be able to communicate it.” The C-suite duo went on to defend why Biogen and partner Eisai believed the original analysis to be incomplete, with Vounatsos referencing a “new analysis” of a more complete dataset where “the T’s were crossed and I’s dotted” that justified filing for FDA approval. Sandrock dubbed the evolution in the company’s view of the data as a “gradual understanding” of what shifts in dosing regimens across various trial participant pools and over a longer timeline, among other issues, meant for its evaluation of aducanumab. Federal regulators and Biogen later provided more complete chronologies on the various issues surrounding the therapy’s trial designs.

We know what’s happened since. Biogen’s reversal that October in 2019 was just the opening act in a drama that would lead to one of the most controversial FDA approvals ever in June 2021—a play with no shortage of regulatory, marketing, advocacy, scientific, and political intrigue and recriminations. Three prestigious scientists on the FDA’s independent advisory committee resigned over the agency’s decision to ignore the panel’s overwhelming rejection of the treatment, Biogen slapped a massive $56,000 list price tag on Aduhelm, insurers refused to cover the drug, doctors refused to prescribe it, and the company revealed in its Q3 2021 earnings report last October the treatment had managed to bring in just $300,000 in sales since being approved. That was against Wall Street forecasts of some $14 million in expected Aduhelm revenues during its first three months on the market.

Then, in November, Biogen abruptly announced Sandrock would retire from his perch as R&D chief at the end of 2021. The following month the firm slashed Biogen’s list price in almost half to $28,200. And in yet another massive setback, just last week the federal agency which oversees the public Medicare insurance program for the elderly recommended strictly limiting its Aduhelm coverage to patients participating in approved clinical trials, citing significant doubts that existing evidence shows Aduhelm’s potential benefit to patients outweighs its risks. Biogen executives reportedly told sales teams they fear just 2,000 patients will have access to the therapy at all in the near future, according to Endpoints News, and massive layoffs are already on the way.

Aduhelm’s story will continue to make industry waves as we see where the drug ultimately winds up. It may also have broader ramifications on competitors looking at Biogen’s drug’s pathway to approval and how events have turned for the company since, on top of adding to long-existing questions about the validity of focusing on amyloid plaque to combat Alzheimer’s.

But what, precisely, led to aducanumab’s disastrous launch? A combination of perverse incentives and an aggressive marketing push to get the first “true” Alzheimer’s treatment to market, the failure to align strategies with sloganeering, and a belief that even the most questionable therapeutics would find a home among the millions of Americans who grapple with dementia, says Mike Rea, CEO of IDEA Pharma and Protodigm.

It begins with a cynical gamble that clearly has not paid dividends. “That’s the part that really bothers me, this thinking that this community doesn’t have anything so they will accept anything that’s on the market, banking on the desperation of Alzheimer’s patients to fuel sales for your sucky drug,” Rea tells me. “Just a belief that the Alzheimer's market is addressable by anyone with anything, and that if you were to launch it, you know, good things will happen.”

And then there’s just bad science. “They chose the most surrogate of markers, they tried to justify the data with small dataset slices, and they didn’t even do particularly well at that,” says Rea. (Readers may have heard that, on top of having zero solid evidence of a clear benefit to patients, the drug has been plagued by side effect and safety concerns and potentially linked to at least one patient death, a 75-year-old Canadian woman who was taking Aduhelm.)

But the foundations of the treatment’s failures were set long before the masses had ever heard of aducanumab. The inability to come up with a rational path to market strategy in favor of a “get approved and sell at all costs” approach was the self-defeating original sin.

Rea compares the scenario to a soccer (that is, the sport called football by the non-American world) striker being perfectly content with scoring a hat trick in a game her team loses 5-3.

“I think the launch at all costs guys were pushing with the false belief that there was a market there,” he says. “Integration is so important. Considering factors such as, is there a market for this drug? Does it have a strong value proposition for patients and the medical system? Or if it

doesn’t actually have a place in the market, do we just sort of ignore all of that—which is what Biogen did.”

Perhaps the most jarring question is: What would have happened had Biogen achieved a modicum of decent sales despite deep skepticism from so many corners of the medical world? Would Sandrock still be at the firm loudly proclaiming Aduhelm’s virtues to a desperate patient market? Would Biogen simply double down on its gambit with a medicine that’s been deemed highly questionable (and potentially useless) by numerous physicians and scientists?

This autopsy is a preliminary one. We still don’t know how Aduhelm’s story will read in the pantheon of hobbled drugs, though prospects for a happy ending seem bleak. Perhaps it could serve as a learning moment for companies tempted to put the cart so far before the horse in a quest for market domination without thinking through non-marketing decisions and crafting a holistic strategy. For now, Aduhelm is merely a therapy whose shortcomings have oscillated between the controversial and the comical.