By Sy Mukherjee
March 21, 2019

Good afternoon, readers.

It was a sad day for biopharma. Yet again, an Alzheimer’s drug hopeful crashed and burned in critical late-stage clinical trials. The victim, this time, was biotech giant Biogen (alongside Japanese partner Eisai), which had placed a massive amount of time and money in a high-risk bet on experimental Alzheimer’s treatments.

The companies announced on Thursday that they would be discontinuing trials of aducanumab. And the news caused Biogen shares to tank nearly 30% in trading, erasing nearly $20 billion of the company’s market value. (For context, as biotech VC Bruce Booth points out, the 130-plus biotech IPOs since January 2015 raised $15 billion.)

A number of analysts across the biopharma spectrum expressed a sort of knowing sadness about this latest failure, which follows a trail of disappointments that’s dogged companies like Eli Lilly, Pfizer, Merck, and countless others. There are no available treatments to address the underlying disease of Alzheimer’s; the last approved therapy, which only treats the condition’s symptoms, was approved well over a decade ago.

Much of the commentary around these failures focuses on the central approach companies have taken in recent years: That is, by focusing on the “beta-amyloid hypothesis,” which places the buildup of a kind of brain plaque at the center of drug development efforts, in lieu of targeting other biological targets.

That strategy has come under increasing scrutiny, as Fortune has previously reported. Our own Editor in Chief (known to regular readers as Cliff) had an expansive and informative piece on the various issues dogging Alzheimer’s drug development in this very column last summer.

The question is whether Biogen’s astoundingly expensive failure will shift the industry’s approach on a meaningful scale. To that end, there are several upstart companies looking to shake things up – including United Neuroscience, which is attempting to develop vaccines to actually prevent Alzheimer’s and other neurological disorders from occurring in the first place.

Speaking of… United Neuroscience’s CEO, Mei Mei Hu, will be speaking at our upcoming Brainstorm Health conference in San Diego in a little more than a week – as will Paul Cox, whose fascinatingly unconventional approach to Alzheimer’s treatment landed Fortune‘s February cover story. In an era where the go-to strategy has failed time and time again, these pioneers’ outside-the-box thinking may very well seep into the mainstream.

And for you fans of The Sopranos, the crime drama classic which debuted 20 years ago – actress Edie Falco, aka Carmela Soprano herself, will also be at Brainstorm Health for a candid conversation with our conference co-chair Arianna Huffington. We hope to see you there.

Read on for the day’s news.

Sy Mukherjee
@the_sy_guy
sayak.mukherjee@fortune.com

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