Aducanamab, FDA Approval, Patient "feelings"

Probably most have seen the news that FDA has approved Biogen’s aducanamab, for the treatment of Alzheimers. I just need to say that I have some direct experience with this drug (well, development and trials) and I’m frustrated that all the advocacy groups are defending this very controversial decision by saying that “The community is suffering and needs this.”

Well, that may be, but being in dire need of a treatment doesn’t mean that any given treatment works, and using that as a justification for approving a $54,000 treatment is insane pandering.

I cannot understand why FDA approved this. At minimum, it needed another P3 at the high doses and early administration to actually know if it works.

For the record, I do NOT work at or with Biogen. But ours is an interconnected industry and I’ve been involved with the trials.

Yeah, I’m very disappointed. It’s not clear the drug helps at all, much less that it helps enough to make it worth the risk of using. And the price tag for this wonder drug is ludicrous.

But that’s the way it goes these days. Cancer treatments where the evidence shows that there’s a 7% chance of extending life by 3 weeks go for $70k a dose.

I could hand out Smarties and get nearly the same results for a LOT less money and if I given them some random letter name that sounds like a Tolkien character it will help people “feel” better - can I get FDA approval?

Lol, I recently wrote my first prescription for Fingolimod. Must be Finwë’s lesser-known 4th son.

I have a D&D character named Sildenafil Morningwood. An elf, of course.

Fun bit of trivia.

Drug companies go out of their way to ensure that these names are difficult and unpleasant. The reason is that once the drug goes off-patent, it will be known by this USAN name. But the trade name will remain protected by trademark. What you don’t want is all the versions- yours and generics- to have the same catchy name.


Son of Cialis Proudstaff?

It would be an interesting creative writing exercise to write a story where all the names are drug names.

As I understand it, its ostensible effectiveness is based on a surrogate measure and not on the outcome of interest. Specifically, the drug lowers levels of brain amyloid but has not been shown to reduce the symptoms/manifestations of dementia. This is a critical point because the medical literature is replete with examples of how surrogate outcomes can be misleading, suggesting benefit when in fact they do harm.

In particular, there remains some debate over whether or not reduction of beta-amyloid deposits is the key to treating Alzheimers. I would say most researchers believe that it is, but this is not a settled fact.

To really evaluate this, the patient should receive a PET scan for beta amyloid, deemed a candidate, treated, and periodically re-scanned. Each of those scans costs about $5,000 (including the imaging agent) .

One thing CMS is worried about is an amyloid scan becoming something that’s done as a matter of course at ~50 years old, like a colonoscopy is. That would be ruinously expensive.

But you are nonetheless correct.

It’s not “some random letter name,” it is Bamanacuda spelled backwards.

Do doo do dodo

I know nothing about this particular drug, and I’ve only read a few short articles about recent research into Alzheimers, so I’m not necessarily talking about this drug in particular.

But my more general position, regarding the FDA, is that there are times when the agency would be a greater benefit to the advancement of medical science if it would allow some drugs and treatments to be used sooner rather than later. I’m a pretty strong supporter, for example, of Right To Try laws, and I have found almost none of the arguments against these laws to be particularly persuasive. As long as everyone in the process–and especially the patient, obviously–is properly informed of the potential benefits, the risks, and the relative weight of those factors, then let people take a chance.

I guess my questions about this particular drug are: What is the actual, medical downside of the FDA’s decision? Are the risks of taking the medication substantial? And if they’re not, what’s wrong with letting people take a chance on using it?

Are your objections mainly economic, regarding the cost and its potential to further inflate healthcare costs without much noticeable benefit? If so, would you support approval of the drug provided it was made available more cheaply by the manufacturer until its efficacy is more conclusively demonstrated (or disproven)?

I’m not claiming to have answers here. But I also think that, as long as everyone involved is making informed decisions, I’m not sure that we always need the FDA to maintain such high barriers designed to protect us from ourselves.

SNL did…

From my perspective, there’s more than I can do justice to in the few minutes I have, so I’ll tl;dr it:

Most drugs have side effects, and these can range from harmless to serious. A drug that imparts little or no benefit means negative side effects for nothing. Patients on aducanamab have to be monitored for brain bleeding. For something that maybe works.

Right to Try is a bit of BS, frankly. First, companies developing drugs can do a lot to enable access. From opening new studies to compassionate use. That’s legal now. But companies are on the hook for whatever happens with their drug during the clinical phase (and after). So when a terminal patient takes something under the “might as well” approach, this can have serious repercussions for the drug development. As a result, companies are loathe to allow this. And right to try doesn’t mean forcing a company to allow access. So in a sense, you already have a right to try, but the company has a right to refuse. And they will exercise that right 99% of the time

Aducanamab costs $54,000 per year. There are 500,000 new Alzheimers cases/year in the US. Do the math. On something that may not work. That’s a cost borne by society one way or another, and it’s one thing if it works. Entirely another if it’s a waste of money.

Finally, under the practice of medicine, any physician can prescribe any drug for any reason. Qadop can decide his alzheimer’s patients would be better served with daily doses of Viagra. So nothing stops “right to try” on the approved side. The insurers may not pay for it, and Qadop may be held to account for his decision, but he can do it (FTR, I am NOT a doctor).

That’s my issue with the “We really need something” argument. You need something that works. Things that don’t aren’t harmless. Economically or physiologically.

OldOlds represents a lot of my thoughts on the topic. I’d just add that the first dictum of medicine is Primum non nocere, or “first do no harm”. When the FDA is approving drugs for general use that have no clear benefit while having clear risks, it violates that dictum.

Leaving the cost aside (but see below), one of the biggest negative effects is that if a genuine candidate drug comes along, it will have to be tested against this drug rather than a placebo (although there is no evidence that this drug is more than a placebo) which would slow down and add enormous expense to the testing. A couple months ago, I started a thread about an article in the May issue of Scientific American in which a new theory of Alzheimer’s was discussed (essentially a breakdown in the blood-brain barrier) and one possible treatment that had had unexpected success with mice. The drug was called IPW (the company that had developed as an anticancer drug is called Innovation PathWays–you’d think an innovation company would have more imagination in naming), but it will now be much harder to test.

Since most of the recipients will be on Medicare, it is the federal government that will bear most of the cost–$56K a year according to the Times.

Incidentally, this is independent of allowing people to try unapproved “hail Mary” drugs if they wish. I’m all in favor of that. It is this formal approval against scientific recommendation that I mind.

This has been linked to before, but it seems the perfect time for a repeat.
Antidepressant or Tolkien

I’ve not managed to ace it yet.

Well, as always it depends. In the case of aducanamab, the endpoint was reduction (actually, I think, no further increase) in B-amyloid, not improvement in cognitive function. So the only way another drug could use aducanamab as a comparator is if that drug also targets B-amyloid depositions. Which, as I mentioned, is the prevailing hypothesis of alzheimers

And again: If I have a developmental drug (and that’s what I do for a living), I am NOT going to let you hail mary-it. When it has an unintended side effect? My problem. If you have a contraindication I don’t know about? My problem. You have anything worse than a neutral experience? My problem. When we run trials we control for all that because we can’t just say “It was a desperate use outside of the intended. Not our problem.”


That’s a Genesis song, right?

Thanks for saving me the trouble of hunting that up!