> Central to their mission was an inside ally: Billy Dunn, the agency’s top regulator of Alzheimer’s drugs. For the plan to succeed, Biogen needed Dunn to become a supportive partner, more than an independent and potentially adversarial regulator. It worked. The FDA played an extraordinarily proactive role, even drafting a road map on how the company could win approval. Several experts said that relationship was not typical and raised serious concerns.
> It was previously known that Biogen and the FDA worked together on Aduhelm. But STAT has learned that the relationship began earlier than previously disclosed, in the spring of 2019, when a top Biogen executive quietly met with Dunn — seemingly in violation of FDA protocols — to enlist his support for a long-shot effort to get Aduhelm approved despite the apparent failure of two clinical trials. And a month later, FDA officials proposed using a regulatory shortcut to get the drug approved — though the agency has claimed it raised that option only this past March. To some inside Biogen, the FDA’s tone made approval seem inevitable.
> By June 2019, only a month after the crucial meeting with Dunn, agency officials in his Office of Neuroscience were so willing to advance Aduhelm that they proposed as one option a regulatory shortcut called “accelerated approval,” according to meeting minutes read to STAT. The move stunned even Biogen’s top executives, who had considered that out of the question for a host of reasons, including the fact that the FDA had never used the pathway for an Alzheimer’s treatment.
Looks like one set of laws and rules for regular people, another for those who have direct access to top regulators. And of course anybody suggesting this may be done for any other reasons than the pure altruistic care for Alzheimer’s patients (even though no trial showed the drug works, but there's still a chance, right?!) would be totally irresponsible.
FWIW, based on https://www.fda.gov/patients/fast-track-breakthrough-therapy..., the "Accelerated Approval Program" appears to be designed for cases where the clinical benefit hasn't been proven, but the effect of the drug on appropriate markers has been.
Here's a specific example from the link above:
>"Using surrogate or intermediate clinical endpoints can save valuable time in the drug approval process. For example, instead of having to wait to learn if a drug actually extends survival for cancer patients, the FDA may approve a drug based on evidence that the drug shrinks tumors, because tumor shrinkage is considered reasonably likely to predict a real clinical benefit. In this example, an approval based upon tumor shrinkage can occur far sooner than waiting to learn whether patients actually lived longer. The drug company will still need to conduct studies to confirm that tumor shrinkage actually predicts that patients will live longer. These studies are known as phase 4 confirmatory trials."
I think the shady bit is that this probably wasn't an appropriate use of that pathway, and that the FDA wasn't acting in good faith.
At the end: "This is an abridged version of a STAT special report." (It doesn't seem very abridged! To do more they would have to give dates of the meetings or something.)
I'm not really sure that would be helpful, what does "improve quality of life" mean? The prescribing guide gives information about how the drug works (or how it's suspected/hoped to work), and it should have detailed information about side effects and benefits with percentages as seen in trials. It is first-party marketing material, so it has to be in agreement with verified data submitted to the FDA.
And people wonder why others wouldn't trust federal instances with health recommendations during the pandemic. This is exactly this kind of stories that undermine the trust in those institutions, and these effects ripple far away in the future...
Apparently even questioning institutions like this makes people Nazis, so I think it is a combination of being harassed for questioning and the government running lotteries and making deals with companies to offer free donuts and alcohol.
I think GP is being a little hyperbolic, but it has been difficult to publically criticize federal health institutions over the past year or two, even for things like this, without being associated with a larger set of anti-institutional political views. In some circles, everyone who subscribes to those views (or doesn't actively condemn them) is a Nazi. The politcal discourse in the USA is unhealthy.
Because you can find actual Nazi circles so I'm positive that you can also find circles that thinks anyone who criticizes federal health institutions is a Nazi as well. Even though it was hyperbolic it still annoyed me because its just SO extreme for no reason. I just feel you shouldn't throw "Nazi" around for any old reason and should be reserved for real ones. ¯\_(ツ)_/¯
If it annoys you, then you should go look to see how people questioning vaccine trials are treated. Reddit frequently front pages videos of them being attacked and punched while being called Nazis with extreme amount of upvotes.
I think it is actually a very common to use the word Nazi liberally, especially among young people with a leftist slant. But my retired left-center mom who watches MSNBC all day gets in on the action too.
Maybe it would be better to reserve the word Nazi for True Scotsmen, I mean True Nazis. This is not what's cool in the political discourse right now.
Very few people can read data for themselves. I certainly can’t.
I’m a highly qualified software engineer. I’m not a data scientist or an epidemiologist.
I work with some every smart data scientists. We occasionally discuss data topics outside their domain. They seem to hit a knowledge wall fairly quickly.
Please don’t ask unqualified individuals to “make their own calls” based on raw data they are not qualified to interpret.
I have to trust they audit the data, trial sites, manufacturing plants, etc… That’s sort of their job. If the people working there don’t want to do that job, they should probably be replaced.
This comment has about as much thought put into it as those who dismiss vaccines outright. Are you really suggesting that every joe and Jane schmo out there read, interpret, and analyze a paper and come to conclusions themselves before trusting a treatment?
The problem is that in the United States, you have a choice between placing your trust in public institutions that are constantly under assault by private firms, like Biogen... Or you have to trust those private firms.
I suppose in the medical field there's also a third party of snake oil supplement vendors, that don't even bother trying to measure whether or not what they are peddling actually cures anything.
Burden is on anyone who assigns value to US currency, as the most likely method of paying for medicare will be stock market manipulation perpetrated by the federal reserve in cahoots with the too big to fail investment bankers.
Who cares if the corporations don't pay taxes when their very existence permits exploitation in order to pay for the same programs their tax dollars would have.
This is so messed up. Time and time again we've seen drugs that target amyloid beta fail to have any effect, and this one is no different.
Not only were the studies inconclusive, but they were only of people with very mild Alzheimer's or even pre-alzheimers and yet the FDA is approving it for any patient with Alzheimer's.
Just stealing billions of dollars from desperate people.
I get the qualms around this approval of a drug that very plausibly does not work, but I feel that too much ire is being directed at the FDA instead of at Medicare for paying for any approved drug. That's the core issue here — not that Biogen is allowed to sell the drug, but that public funds will be drained to pay for it.
Yeah sure this might not work, but the FDA is reasonably confident it doesn't make things _worse_, and if it does actually work, there's immense potential for lives improved. Alzheimer's is truly a devastating blow to any family with a member who get it. So why not approve it? Bare minimum, we'll get more data.
The data does not show that it works, and it was on a very specific sample (pre-alzheimers or early Alzheimer's). The drug costs $50k so they are profiting from desperate people.
And yes, it can make things worse:
"Most patients with AD (up to 75 percent) have a specific gene, called apolipoprotein E (APOE) ε4 allele; having this particular gene places a person at great risk of developing Alzheimer’s disease. Unfortunately, when AD patients with the APOE4 gene are given drugs like Aduhelm they are much more likely to develop brain edema and cerebral microhemorrhages. Indeed, in the BIOGEN trials, almost 50 percent of the APOE4 patients developed brain edema and hemorrhaging. In addition, these symptoms were accompanied by malignant hypertension and epileptic seizures."
> Yeah sure this might not work, but the FDA is reasonably confident it doesn't make things _worse_, and if it does actually work, there's immense potential for lives improved. Alzheimer's is truly a devastating blow to any family with a member who get it. So why not approve it? Bare minimum, we'll get more data.
The reason is right there in what you're saying: the FDA is meant to protect people from predatory drug companies who know they are desperate to try anything to help their loved ones. If Biogen were selling homeopathic Alzheimer's cures, would you still think they should have been approved?
Any data you will get from this approval will be very hard to interpret, as no randomization is done, so there is no proper control group.
Moreover, proven safety is not sufficient to approve a drug. For experimental drugs without alternative treatment, it can be given as part of the compassionate use program. I think you could make an argument that the drug fits there, but approval sends the wrong message (ie. proven safety AND efficacy).
Normal procedure for the FDA is to approve only effective drugs, not just drugs that are safe but might not actually work. If on a whim they've decided to change that, Medicare needs to be updated to be more skeptical of FDA-approved drugs.
Unfortunately, our government is not very good at things like passing laws, so likely it will be quite some time before Medicare is adjusted. Very clever exploitation of an opportunity to basically steal billions of dollars from the public. I can't even be that mad, it's such an evil genius plan. Nicely done, Biogen.
No. This is an intentional accelerated approval. Approved based “likelihood of clinical benefit based on bio marker changes”. The FDA is NOT saying it definitely works, it’s saying there is enough data to give early access.
CMS can do a “Coverage Determination” as they often do and either not cover it at all (unlikely) or severely limit it’s use (likely) potentially to patients who agree to be a part of a registry where outcomes are collected.
42 comments
[ 4.2 ms ] story [ 91.3 ms ] threadtl;dr, what's the backchannel and will this become an area of concern?
Excerpts:
> Central to their mission was an inside ally: Billy Dunn, the agency’s top regulator of Alzheimer’s drugs. For the plan to succeed, Biogen needed Dunn to become a supportive partner, more than an independent and potentially adversarial regulator. It worked. The FDA played an extraordinarily proactive role, even drafting a road map on how the company could win approval. Several experts said that relationship was not typical and raised serious concerns.
> It was previously known that Biogen and the FDA worked together on Aduhelm. But STAT has learned that the relationship began earlier than previously disclosed, in the spring of 2019, when a top Biogen executive quietly met with Dunn — seemingly in violation of FDA protocols — to enlist his support for a long-shot effort to get Aduhelm approved despite the apparent failure of two clinical trials. And a month later, FDA officials proposed using a regulatory shortcut to get the drug approved — though the agency has claimed it raised that option only this past March. To some inside Biogen, the FDA’s tone made approval seem inevitable.
> By June 2019, only a month after the crucial meeting with Dunn, agency officials in his Office of Neuroscience were so willing to advance Aduhelm that they proposed as one option a regulatory shortcut called “accelerated approval,” according to meeting minutes read to STAT. The move stunned even Biogen’s top executives, who had considered that out of the question for a host of reasons, including the fact that the FDA had never used the pathway for an Alzheimer’s treatment.
Here's a specific example from the link above: >"Using surrogate or intermediate clinical endpoints can save valuable time in the drug approval process. For example, instead of having to wait to learn if a drug actually extends survival for cancer patients, the FDA may approve a drug based on evidence that the drug shrinks tumors, because tumor shrinkage is considered reasonably likely to predict a real clinical benefit. In this example, an approval based upon tumor shrinkage can occur far sooner than waiting to learn whether patients actually lived longer. The drug company will still need to conduct studies to confirm that tumor shrinkage actually predicts that patients will live longer. These studies are known as phase 4 confirmatory trials."
I think the shady bit is that this probably wasn't an appropriate use of that pathway, and that the FDA wasn't acting in good faith.
https://www.msn.com/en-us/news/us/inside-e2-80-98project-ony...
At the end: "This is an abridged version of a STAT special report." (It doesn't seem very abridged! To do more they would have to give dates of the meetings or something.)
"The FDA found this drug to improve quality of life Vs a placebo, p<0.005".
And if, during use of the drug, that statement becomes no longer true, withdraw use for all new patients.
Maybe it would be better to reserve the word Nazi for True Scotsmen, I mean True Nazis. This is not what's cool in the political discourse right now.
I’m a highly qualified software engineer. I’m not a data scientist or an epidemiologist.
I work with some every smart data scientists. We occasionally discuss data topics outside their domain. They seem to hit a knowledge wall fairly quickly.
Please don’t ask unqualified individuals to “make their own calls” based on raw data they are not qualified to interpret.
I suppose in the medical field there's also a third party of snake oil supplement vendors, that don't even bother trying to measure whether or not what they are peddling actually cures anything.
Aren't we just a bunch of greedy monkeys?
PS: Therapy costs $56,000/year. My question stands.
PPS: Seems like Medicare will pay for it, so burden is on taxpayers.
Who cares if the corporations don't pay taxes when their very existence permits exploitation in order to pay for the same programs their tax dollars would have.
The circle jerk of freedumb.
Not only were the studies inconclusive, but they were only of people with very mild Alzheimer's or even pre-alzheimers and yet the FDA is approving it for any patient with Alzheimer's.
Just stealing billions of dollars from desperate people.
Yeah sure this might not work, but the FDA is reasonably confident it doesn't make things _worse_, and if it does actually work, there's immense potential for lives improved. Alzheimer's is truly a devastating blow to any family with a member who get it. So why not approve it? Bare minimum, we'll get more data.
And yes, it can make things worse:
"Most patients with AD (up to 75 percent) have a specific gene, called apolipoprotein E (APOE) ε4 allele; having this particular gene places a person at great risk of developing Alzheimer’s disease. Unfortunately, when AD patients with the APOE4 gene are given drugs like Aduhelm they are much more likely to develop brain edema and cerebral microhemorrhages. Indeed, in the BIOGEN trials, almost 50 percent of the APOE4 patients developed brain edema and hemorrhaging. In addition, these symptoms were accompanied by malignant hypertension and epileptic seizures."
But I’m not so sure that decoupling the decision is so easy. Patients get very upset if insurance doesn’t cover something…
The reason is right there in what you're saying: the FDA is meant to protect people from predatory drug companies who know they are desperate to try anything to help their loved ones. If Biogen were selling homeopathic Alzheimer's cures, would you still think they should have been approved?
Moreover, proven safety is not sufficient to approve a drug. For experimental drugs without alternative treatment, it can be given as part of the compassionate use program. I think you could make an argument that the drug fits there, but approval sends the wrong message (ie. proven safety AND efficacy).
Unfortunately, our government is not very good at things like passing laws, so likely it will be quite some time before Medicare is adjusted. Very clever exploitation of an opportunity to basically steal billions of dollars from the public. I can't even be that mad, it's such an evil genius plan. Nicely done, Biogen.
It would be better if they allowed any drugs to be sold, but just labeled them as "safe" or "effective".
The reasonable way to kill this, by the way, is for Medicare to decline to reimburse for the drug. It’ll be approved, but it’ll be dead on arrival.