I would like to recommend this piece at Stat about the details of the Biogen aducanumab approval. It’s behind the paywall, but it’s a deeply reported piece from Adam Feuerstein, Matthew Herper, and Damian Garde about how in 2019 Biogen launched an effort to get their apparently failed drug approved by the FDA anyway. They called it “Project Onyx”, renamed from the original “Project Phoenix” after Biogen’s lawyers objected to the implications of that one.
A key moment was a face-to-face meeting between Biogen’s Al Sandrock and Billy Dunn at the FDA’s Office of Neuroscience. This took place when the two were separately attending a neuroscience meeting in Philadelphia, and it was not in any way an official contact between the company and the regulatory agency. This appears to have been contrary to FDA policy, on the face of it, and is at the very least worth knowing about – a former Biogen employee told Stat that after the meeting, “It was clear that Billy Dunn was an ally, so the job for Biogen became figuring out how to support his efforts within the FDA“. A month after the meeting, the FDA proposed the idea of an accelerated approval designation for aducanumab to Biogen, a huge victory which seems to have taken even Biogen’s executives by surprise. And the FDA’s official statements about how they came to the accelerated approval idea say nothing about the Dunn/Sandrock meeting.
The Stat article has plenty of inside-baseball details on the strains inside Biogen over the last few years, as the company went from being flush with money and new drug approvals to finding itself depending on – of all things – getting an Alzheimer’s antibody approved. I often wondered what people in the company thought about that, and I kept imagining David Byrne’s voice saying “Well. . .how did I get here?” There’s also an excellent look at how the company charged ahead in 2019 with an interim of the aducanumab results, a decision that led to biostatistician Thomas Fleming resigning from the monitoring board. But the company was confident of a good readout, and at that point they really needed one. What they got instead was a “halted for futility” decision. If you trust that one, then the FDA approval never should have happened. If you trust the FDA approval, then the futility call was an idiotic and premature mistake. I don’t see much room for a third option.
It’s important to realize just how weird the agency’s actions were during the entire aducanumab business. That’s underscored by the people who have resigned in protest from the outside advisory committee after its hugely negative vote was completely ignored by the agency. From the outside, it really looks now as if the FDA made it its mission to get this drug on the market one way or another. I’m not saying that’s exactly the decision they made, but their actions would have been no different if that were the case. The article also has details about the first formal meeting between Biogen and the FDA in June of 2019 – that’s where the accelerated approval idea came up, and frankly the meeting reads like the agency reading Biogen’s most optimistic spin back to the company. No wonder the Biogen execs were a little disoriented.
Meanwhile, none of that was conveyed to the advisory committee. You’d think that the idea of accelerated approval versus outright rejection would be worth hearing about, along with the reasons for thinking that, but the committee appears to have been sandbagged. They held their meeting in a world that had already been superseded by one in which the FDA was pushing aducanumab for approval. In retrospect, that makes the severed-hemispheres nature of the briefing documents easier to understand. The earlier sections were from the Go Biogen! Go Aducanumab! part of the FDA, the decision-making part as it turned out, while the extremely unfavorable review from the FDA’s statisticians at the end was from the What Are These Numbers Really Telling Us part, which is where the advisory committee was as well.
Silly people! They should have taken off their Statistician and Clinician hats and put on their Drug Approver hats. I mean, it says right there in the agency’s charter that its mission is to Give People Hope One Way or Another, right? That its job is to Approve Drugs, which means that you can defer for years the question of whether they actually do any good? And that if a given drug candidate actually has stronger evidence that it does harm, that this can be cancelled out by the amount of Hope Delivered? Billy Dunn and Janet Woodcock can apparently tell you where those parts of the mission statement are, and the rest of us just need to Believe, to Hope, and to Trust. What a beautiful sight it all is.