Answers: Did The FDA Mess Up With Aduhelm?
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The Story of Aduhelm
Last time, I gave a rundown about why the new FDA approval for the Alzheimer’s drug Aduhelm was problematic because it exposed everything wrong with the approval-coverage-reimbursement entanglement. I asked for all of your thoughts.
Since then there have been SO many developments it’s hard to keep track. And this is coming from a person who keeps up with drama between YouTubers.
This piece talks about how Biogen had a weirdly close relationship with someone within the FDA. Three members of the FDA expert committee resigned over the approval. A major patient advocacy group for Alzheimer’s patients came out against the drug price. The FDA revised the label for Aduhelm to only use it in patients with mild cognitive impairment/dementia. Large academic medical systems are refusing to give the drug. Janet Woodcock, who approved the decision…called for an investigation into the decision? And this is without a permanent head of the FDA!
The responses I got about Aduhelm were virtually all against it, but below were a few answers that I thought were generally different in their perspective.
Drugs Can Go Generic, Services Can’t
“No doubt spending $56k on services would improve a variety of outcomes. Same could be said for a lot of diseases. However, services don’t go generic. Drugs can. Replacing services with manufactured goods offers societal value even if near-term higher overall costs (like paying a higher but temporary mortgage for your own home when you’re facing rising eternal rent).
So what’s happening with biosimilars and whether Adu can “go generic” (become inexpensive) is important.
As for whether it’s too much, that depends on where this step leads us. If it incentivizes innovation that results in us shelling out a Humira-sized reward (eg $15b/year for 15 years) for each of 30 drugs but then we’ve vanquished Alzheimer’s dementia, then that total spend is way below even what ICER says is worth paying over the next few decades to achieve that goal. Few more thoughts on that here:
[NK note: Considering that Alzheimer’s drug development is basically a graveyard, it’s probably good to have something that re-incentivizes development. I’d be curious to see if it incentivizes new hypotheses on how to tackle Alzheimer’s or a bunch of ehhh drugs that know they can get to market through an existing belief like amyloids. The unfortunate reality is that drug development is somewhat of a zero sum game because of the finite number of patients + dollars that can be deployed, so attracting drugs to bad hypotheses could potentially be a net negative to the space. But it's also possible that a bunch of incremental drugs that tackle different contributors to the disease could be a gamechanger, so maybe having one amyloid drug in the market that gets tested in new combinations is good? Idkkk]
Plaque? More like waque
“Yes, I do think the FDA made a mistake approving Aduhelm, but I think it was the best decision for this country. First, this drug is going to prove once and for all (hopefully) whether or not the amyloid hypothesis is the true reason for Alzheimer’s disease. What about the tau hypothesis? The data shows that this drug successfully removes plaque, so now we can answer the question: does removing plaque improve cognition and ultimately cure Alzheimer’s? Like many things in life, this drug is one of the first movers, but I do not think it will be the end all be all and be the ultimate champion of this disease. From this drug a lot of things will be learned and a new version of the drug with all the benefits, but none of the downfall will be developed and cure this disease. Remember, by 2050 it is expected that 50% of people over 65 will either have Alzheimer’s or be the caretaker for someone who does.
The other reason I like this approval is it will be the final straw that breaks the camel's back on drug pricing reform. Hopefully Congress can finally get their act together and regulate this side of the industry. As someone who works in a startup biotech I completely understand how this regulation could stifle innovation and scare off investors and entrepreneurs, but also as someone in this industry, I look forward to the challenge and will just be more determined. People will still become overnight billionaires and develop cures for any disease, but society will not go bankrupt in the process and the money saved can just be funneled back into STEM projects/education to further drive groundbreaking innovation.”
You had one job
“This is a watershed moment for the FDA. Like the defund the police movement, we’re watching the defunding of the FDA- by their own volition. No longer can we trust our government to approve only effective, safe medications. Now, we must rely on the free market.
The FDA never really had this bar to keep us safe and approve only effective drugs. It was a Fugazi, it just appeared that way.
- Vioxx, a drug that was approved and later pulled because it turns out that it actually killed people
- Chantix, a drug that was approved and later we figured out that it was totally useless except in select populations
- Etc etc etc
In life, most of us, not just clinicians, would prefer to be on auto pilot, versus thinking about individual decisions. Now, we know we can’t rely on the FDA, and will think more about every treatment decision, marrying data with patient preferences to make evidence based decisions.”
[NK note: If we had 0 bad approvals ever it would mean the FDA is being TOO conservative and great drugs that should have been approved are taking too long to get to market while people are suffering with the disease. This is the everpresent balancing act of speed, efficacy, and safety.]
Is incentivizing development with mehh drugs...good?
“Another recent-ish FDA approval in a related space that caused some head scratching was Radicava for ALS in 2017. The approval was based on a post-hoc analysis of a responder group from a trial in Japan over just 6 months looking at a functional endpoint. The drug has a list price of $146k a year not taking into account costs for the infusions that patients must take. For a very modest benefit the patient has to have an infusion from a medical professional every day for 2 weeks on, then 2 weeks off, then 2 weeks on again, forever. If you run the numbers, the amount of extra time / life they get is pretty much spent getting the infusions. 5 years later, Mitsuibishi Tanabe is sharing real world data analysis (just like you described for Biogen) but there haven't been follow on explanatory trials. As a taxpayer and scientist, this is not good practice. As a disease advocate, this has been a lifeline. In ALS we've had 60 failed trials and investing in the space was seen as a fool's errand. The last approval before Radicava was Riluzole in 1995. Now that Radicava's been approved we see major interest from half a dozen big pharma companies and a couple dozen biotechs all looking to divide and conquer the genetic subtypes of disease, plus innovation in the measurement space and more investment in the search for biomarkers. Academics are increasingly collaborating to perform big platform studies and the advocacy organizations have made great strides in garnering political support in the US (no doubt helped by the Ice Bucket Challenge). So are these approvals good or bad? Yes.”
Nikhil aka. “also fighting hard for approval and payment"
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