Aducanumab Approval, Part 2

So how did a drug with such dubious benefit get approved? At best, another clinical trial might be warranted, but certainly not approval. It's a result

1. of a huge campaign by a company (Biogen) that would not accept the failure of its drug
and
2. of pressure from patient organizations like the Alzheimer's Association (which receives major money from pharma, including Biogen and its Japanese partner, Eisai).

The company campaign began in spring 2019, after its Phase 3 trials were stopped for futility after an interim review. A long, detailed, and excellent STATnews article published this week, drawing on insider sources, tells a fascinating but troubling story. The last-ditch effort to get approval was originally called "Operation Phoenix," but was re-titled "Operation Onyx." Biogen managed to get Billy Dunn, Director of the Office of Neuroscience at the FDA, on their side, to the point that he worked closely with them to provide a roadmap for approval, very inappropriately.

After the groundwork was laid for an approval of aducanumab despite the negative advisory committee recommendation, and prior to the announcing of a final decision, the patient organization campaign was carefully timed. In early May, the Alzheimer's Association launched a big campaign seeking to build grassroots support for drug approval. The "More TIme" campaign worked to pull at heartstrings with celebrity endorsements and poignant personal stories. Full-page ads were taken out in the Wall Street Journal and USA Today, and focused on what "more time" would mean to Alzheimer's patients and their families. There were google search ads, Facebook and Twitter and Instagram and LinkedIn posts. The campaign succeeded in getting over a million people to express support in petitions.

After the approval, the Alzheimer's Association spoke of victory:

As the first FDA-approved drug that delays decline due to Alzheimer’s disease, the approval of aducanumab (Aduhelm™) is a victory for people living with Alzheimer’s and their families.

Comments on articles including this one give the flavor of the passion with which some people want to try this unproven therapy.

Denying a medicine which might work is far more worse than approving one that might not work! Do you agree in the case of Alzheimer’s?

The negativity of these old fashion mentality is what has driven new discoveries to a halt. I don’t suffer from Alzheimer’s nor know anyone close to have been dx w it but we need to start somewhere. Prescribing the pharma will only help w research. Get in line MD.

Alzheimer’s is a horrible disease. If the medicine has a chance of success then prescribe it.

And public officials seem to be buffaloed. A Politico article said that not only are public officials mute about the approval, they are hesitant even about making a fuss about the pricing (about which more in another post):

[Politicians are] worried they’ll be seen as dashing desperate patients’ hope for an Alzheimer’s treatment — even one that may provide little or no benefit. The FDA’s controversial approval of Biogen’s drug, known as aducanumab or Aduhelm, has caught both political parties flat-footed ...Everyone is a bit terrified by Alzheimer’s, so the average person hears about the FDA approval of a treatment, and they don’t know about the controversy over whether it works or not,” said Craig Garthwaite, a health economist at Northwestern University’s Kellogg School of Management who lambasted FDA’s Aduhelm approval. “They hear there’s a new treatment and, that’s great, it’s a sign of hope. Do you want to be the politician who says, ‘I want to take that away from you?’”

Evidently, the public opinion campaign with its drumming up of support for this bogus drug has had its desired effect, creating cowardice to speak about the realities. Subsequent to the publication of the Politico article, two senators did speak out about pricing, but were careful to praise the drug:

Even as they criticize the price, however, Cassidy and Warren still stopped short of directly criticizing Biogen. They offered praise for the drug’s approval, too, calling it a “historic, watershed moment” in the history of the disease.

Public Citizen - who does not have to get elected - did not share this hesitancy. Their long public letter to HHS Secretary Xavier Becerra - which I recommend reading in full - begins as follows:

Public Citizen is writing to express its outrage over the Food and Drug Administration’s (FDA’s) indefensible decision to approve Biogen’s aducanumab (Aduhelm) for treatment of Alzheimer’s disease despite the lack of evidence that the drug provides any meaningful clinical benefit plus the fact that the drug has a well-documented risk of potentially serious brain injury. The FDA’s decision to approve aducanumab for anyone with Alzheimer’s disease, regardless of severity, showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.

They go on to ask for resignation of key officials in approving aducanumab, including FDA acting head Janet Woodcock and Billy Dunn. They also ask that the Office of the Inspector General for HHS investigate the relationship and "close collaboration" between the FDA and Biogen prior to Aduhelm approval. In addition, they want rescission of the bogus approval:

You should direct the next Acting FDA Commissioner to consider whether the agency’s approval of Biogen’s BLA for aducanumab should be withdrawn.

Those who pushed for approval seem eager to foreclose any discussions of rescission. In an interview, there was this question and answer with Acting FDA Head Janet Woodcock:

Question: "There’s been some reaction that every time this criticism comes up, the FDA just dismisses it outright and doesn’t really meaningfully engage on it —doesn’t do soul-searching. … Should the FDA do some soul searching? Should you and the FDA be trying to respond more directly to these critics?" Woodcock's reply: "I think we will have some more public soul-searching type of discussions on accelerated approval itself, but the soul-searching when a decision is made goes on before the decision, and once we’ve made the decision, we’ve made the decision."

Similarly, the head of the Alzheimer's Association wants to end discussion of the approval:

Harry Johns is ready to stop talking about whether or not the Food and Drug Administration should have approved Aduhelm, the divisive new Alzheimer’s treatment that got the green light last week. “Dwelling on the approval at this point is not productive for those who can benefit from the treatment,” said Johns, the CEO of the Alzheimer’s Association. The “negative voices” focused on criticizing the decision, he said, are “not pro-patient.”

But, if the aducanamab approval is not rescinded, what will happen and what are the consequences? More on that in another post.