How One Alzheimer’s Drug Is Changing the U.S. Drug Approval Conversation
April 14, 2022
After Medicare’s decision to restrict coverage of the controversial new Alzheimer’s drug Aduhelm, we look at how this one drug has forced the nation to reexamine how to balance desperate patients, incomplete evidence and larger economic realities.
Scroll down to listen to the full episode, read the transcript or find more resources.
For more context on this decision, revisit our episode on from when it was first proposed, our earlier interview with FDA advisory committee member Caleb Alexander, and our special conversation series “The Aducanumab Aftermath” from June 2021.
Dan Gorenstein: For the past 10 months, a single drug has captured its share of headlines.
Ax: It’ll also go by the brand name Aduhelm
DG: The FDA shocked the health care world last June approving Aduhelm, also called aducanumab.
The evidence was limited — some people with early onset Alzheimer’s may decline more slowly, and the drug carried side effects like brain bleeding.
Not a single member of FDA’s expert advisory committee voted to approve it.
But the FDA did, and then drugmaker Biogen priced the new drug.
Ax: The treatment costs an average patient about $56,000 every year.
DG: Early this year, Medicare proposed only covering the drug for a tiny fraction of the million plus people who could benefit.
And in the first week of April, after months of lobbying, Medicare finalized its decision.
Today, how one drug has forced the nation to reexamine how to balance to desperate patients, incomplete evidence and larger economic realities.
From the studio at the Leonard Davis Institute at the University of Pennsylvania, I’m Dan Gorenstein, this is Tradeoffs.
Phil Gutis: So yesterday morning, car was there at 9:00, hopped in the car, drove to Toms River, which is about an hour and a half away, and sat there for about an hour and a half while the drug was infused and got back in the car and came home again. So it’s about a four and a half, five hour adventure once a month.
DG: Phil Gutis has spent a few hours every month for much of the last five-plus years sitting in a medical office getting Aduhelm pumped into his arm.
Phil enrolled in Biogen’s randomized clinical trial for the drug almost immediately after he got his diagnosis of early onset Alzheimer’s at age 54.
When he began, Phil was unsure whether he’d get the drug or a placebo, but either way, he kept his hopes in check.
PG: The situation with Alzheimer’s drugs was a junkyard, a junkyard of failed efforts and failed attempts. So I did not believe that aducanumab was going to make a difference. I participated in the trial because I didn’t want my nephew and my nieces to have to deal with this.
DG: A couple years into his diagnosis, Phil walked past a theater with his husband in their little Pennsylvania town an hour north of Philly.
PG: I looked at him and I said, “Did we see a show here recently?” And he said, “Yeah, Guys and Dolls.” And I was like. “Hmm. I don’t remember. I don’t remember Guys and Dolls at all.” And he said, “Well, maybe go listen to some music, see if that helps.”
Clip: Guys and Dolls
PG: Nothing. None of the music. Nothin. And I remember sitting on my bed, I guess it was the next morning and saying, “It’s coming, isn’t it?” And we both felt, yeah, it was coming. The decline had begun, and it was going to get worse from there.
DG: Phil’s 60 now, and he compares living with Alzheimer’s to learning to walk on the ceiling.
He forgets the names of his dogs, of restaurants he’s been to.
He forgot that he and his husband had recently redone their deck.
But that decline he knew was coming that morning the Marlon Brando show tune eluded him, that he’s avoided.
And he thanks Aduhelm.
PG: I’m not perfect. It’s not been a cure. But it’s allowed me to continue to participate. I’m still talking. I’m still doing interviews. I can still write. None of that was guaranteed five years ago.
DG: Phil feels lucky.
He believes Aduhelm has delivered on its promise to slow his cognitive decline.
That’s why the public debate — culminating in Medicare’s final ruling last week — has left Phil feeling invisible.
PG: I believe in science. I really believe in science. I understand science. I understand that I’m just an anecdote. They need the data and stuff like that. But the reactions that we’ve seen to Aduhelm have just been almost borderline vicious, and I know I’m not proof, but it’s working. And just feeling that whole five years of my life just being dismissed because it’s not statistically significant.
DG: The final decision from CMS was mostly the same as the proposal they put out in January.
Medicare remains unconvinced that Aduhelm actually works, so it says it will only pay for the drug for people enrolled in clinical trials to gather more evidence.
The agency did make a few tweaks.
First, it expanded coverage to include clinical trials approved by the FDA or National Institutes of Health, as well as trials run outside of hospitals.
And second, it said future drugs that target Alzheimer’s the same way Aduhelm does could be covered by Medicare if those drugs have stronger evidence and go through FDA’s traditional approval process.
PG: Opening it up to non-hospital settings is important. There are a lot of people who don’t live near major hospitals who maybe now will have access. I think opening the door to these other drugs that are coming in the pipeline is very important. So I think tweaking was the right word. They tweaked. They didn’t listen. They sort of just said, “Sorry, sorry, folks. If you really feel this drug has helped you, sorry. We’re just not persuaded.”
DG: Phil and a few other people living with Alzheimer’s actually asked for and got a meeting with Medicare in January before the final decision was made.
They shared their stories, why they wanted Aduhelm to be covered, and Phil felt hopeful leaving the meeting.
PG: But at the end of the day, you know, it didn’t change anything, obviously. I do think it’s important that as these conversations continue, and I know they will, that those of us living with this disease who are in the early stages who can participate need to be at the table.
DG: And do you feel like you’ve been at the table?
PG: I think we are getting at the table, but still very shallowly.
DG: Phil thinks patient voices need to count for more in these kinds of decisions, that they’re experiences and perspectives have been too easily dismissed.
PG: And again, I believe in science. I really do. But that is the challenge, right? To believe in science but to feel so strongly that that patient perspective just gets lost. And I don’t know what the answer to it is, but that is in some ways the greatest frustration.
DG: Phil has two infusions of Aduhelm left in his current trial.
After that, he’s hopeful he’ll be able to get into one of the new clinical trials.
But if he can’t, he says he’ll probably pay for the drug himself — nearly $30,000 a year.
PG: Haven’t made that final decision, but I think I will end up paying for it. It’ll be a hit into the reserves that we’ve been building for dealing with life and retirement and this disease. But if we have to, we’ll pay for it. Feeling all along that, boy, this is unfair because I am on Medicare. And it’s kind of a yet another punch to think I’m on Medicare, I put in my money, and when I needed it, it wasn’t there.
DG: When we come back, what this decision could mean for the future of drug development in the U.S.
DG: Welcome back.
Holly Fernandez Lynch spends a lot time thinking about people like Phil.
Holly Fernandez Lynch: I really do have so much sympathy for patients who lack good treatment options and who are frustrated by this kind of decision.
DG: Holly is an assistant professor of medical ethics and law at the University of Pennsylvania. She studies the FDA drug approval process, particularly for conditions without existing treatments like Alzheimer’s and ALS.
HFL: These are areas where we’ve had a lot of dead ends in drug development. And so I’ve started thinking a lot about how these patients can access investigational products or products before we really have certainty that they are beneficial.
DG: As important as access is for patients with few, if any, options, Holly feels CMS made the right call by limiting coverage of Aduhelm.
HFL: CMS was left to clean up the mess from that mistake in approving Aduhelm in the first place.
DG: Mess may be a strong word to describe the FDA green-lighting a drug, but the facts do raise questions.
The FDA and Biogen worked closely throughout the process, some argue too closely.
The agency ignored the almost unanimous opinion of its expert advisors who wanted the FDA to block the drug.
And the FDA used a process that requires less evidence — called “accelerated approval” — if that drug meets an unmet clinical need.
HFL: It’s really a great case study of all of these different areas of government regulation and the ways that things can go wrong, as well as the ways that I think on the Medicare side, things can go right.
DG: Have you taught this case study yet?
HFL: I’m about to do it tonight.
DG: Are you really?
HFL: Yes. I teach a law and policy course for non-lawyers. And it just so happened that I was teaching FDA law tonight. So we are going to be spending quite a bit of time on this case.
DG: And what are the takehomes for that class that you’re hoping to give the students?
HFL: So I’m using it both to demonstrate some concerns about FDA’s regulatory standards and whether they are, in fact, getting weaker over time, and how we should expect the regulator to balance speed and certainty. And talking about the different kinds of errors that can happen. You can err in going too slow and withholding a product that could be potentially beneficial. You can err in going too fast. Right? And putting something on the market before we are confident that it works. And in particular this drug, this Aduhelm drug has some significant safety concerns with it.
DG: In Biogen’s clinical trials for Aduhelm, four out of 10 patients experienced either brain swelling or bleeding.
Only a few cases were serious enough to force the patients out of the trial and off the drug.
HFL: And then we’re going to be using it to talk more about drug pricing. And why do we find ourselves in this position of really being held hostage to what the company says the price is going to be. First, they say $56,000, then they say $28,000 because they see the writing on the wall that people are upset that this product got approved in the first place. But why is it that Medicare can’t negotiate prices? And what can payers do to force companies to produce evidence when FDA as a regulator seems to be falling down in that regard?
DG: It’s really interesting. I wish I was auditing that class.
DG: So what does this whole Aduhelm experience mean for the future of Alzheimer’s drugs?
HFL: So there are a couple of other drugs in the nearing submission to FDA. I don’t suspect that companies that are so far along in the process are going to pull their drugs back and say, forget it, we’re just going to ditch this thing that we’ve already put loads and loads of money into, right? But I do think it will have an impact on the landscape, not only in Alzheimer’s, but across drug developers, about what government regulators are going to be willing to put up with, right? So if FDA standards remain low, then payers, whether it’s Medicare or private insurers, are going to say, no, we need more evidence for this. Now, FDA, they would really object to me saying they’re lowering their standards, right? What they say is, no, the statutory standard is the same. It’s safe and effective for its intended use. We just have flexibility in the kind of data that can be used to meet that standard. But flexibility around the data means that they are accepting weaker data for approval.
DG: You bring up how this could impact the broader drug development landscape in the U.S., Holly. Let’s talk more about that.
I know you think there are three specific areas where we may see some real change as a result of this Aduhelm experience.
The first is with the accelerated approval process we mentioned earlier.
HFL: Yeah, accelerated approval was supposed to be this tradeoff — early access, evidence later. If the evidence doesn’t come through, we get the products off the market. And the challenges around that that we’ve seen is that companies are not getting their confirmatory trials done or they’re not getting them done quickly enough or even when they get them done, if the evidence doesn’t support the product being beneficial to patients, FDA has a hard time pulling the products off the market.
DG: The whole idea is that in exchange for getting a drug to market faster, companies gather more evidence and then the FDA pulls the drug if it’s not really working.
You are saying that’s not happening, which seems troubling.
How is Aduhelm changing the conversation around this, do you think?
HFL: This was something that those of us kind of in academia and regulatory wonks have been paying attention to for a while now, concerns that the accelerated approval pathway was going too far. And now I think that the real change is that you have policymakers who are saying we need to do something about this pathway because what it’s allowed is a reduction in the evidentiary basis for drug approval. So I think the conversation has changed by drawing attention to this and pushing policymakers to come up with some concrete reforms that I think are very likely to pass.
DG: Like what?
HFL: Some of the reform proposals are to push companies to have their confirmatory studies designed and approved by FDA before the accelerated approval is issued, to get your confirmatory trials done within a certain period of time, three years, five years, or your accelerated approval is going to automatically expire. And then the last thing I’ll mention is trying to make it easier for FDA to withdraw products if they fail to demonstrate benefit.
DG: Let’s move on to this second piece that you think could really change as a result of Aduhelm — the role of payers like Medicare in determining who gets access to the new drugs. Historically, if the FDA approved a drug, Medicare paid for it. Full stop. Now that that’s different, do you think we’re likely to see more of that going forward?
HFL: Absolutely. We have people talking about drug prices and all the ways that the government should be reigning in drug prices and allowing Medicare to negotiate on price is something that a lot of people have been talking about, right? Value based pricing seems to be a great compromise, meaning that we are only going to pay for your drug if it demonstrates benefit. If you fail to do so, we’re going to pay less until you demonstrate that this is a good thing for patients.
DG: And you really feel like Aduhelm might be the straw that breaks the camel’s back in how we’ve paid for drugs heretofore.
HFL: I think so. I mean, there was just so much controversy around the price that Biogen picked for this drug and this concern that they could just pull a number out of thin air. It was not based on their research and development costs, for example. It was based on what they thought the market would bear. And they were wrong about it. But we can’t always rely on this level of outrage to force a company to reduce its price. I think the government is going to have to step in.
DG: So let’s get to your last big takeaway, Holly — the role of patients and patient advocacy groups.
Aducanumab has really put a spotlight on this.
And we’ve talked with several patients — including one at the top of this episode, Phil — who spoke powerfully and forcefully about why he wants Medicare to pay for the drug.
We know groups like the Alzheimer’s Association have lobbied hard to get Aduhelm covered.
How do you see the patient’s role in all of this?
HFL: Patient perspectives is something that Congress has explicitly told FDA that it must do. And there’s not a lot of clarity about what that means. So what I think is clearest is if you have a question about whether a particular benefit is a meaningful benefit to patients, that is something where it’s very valuable to hear from patients. It’s less valuable, in my opinion, to hear from patients, “You should approve this drug because we have nothing better.” Because what that means is that the regulatory standard would be if there’s no other treatment options, let’s just let it rip on the market and we’ll just provide things that have some glimmer of hope. Because what we really would hate to have is a circumstance where patients today, they can try things without certainty. And patients who get diagnosed with the same disease 10 years from now are stuck in the exact same position because companies have not been forced to produce that evidence that would lead to benefit and improvement over time.
DG: What do you base that assumption on that we will see innovation stagnate?
HFL: FDA stands as a gatekeeper and says to companies, you cannot market your product until we say that you’ve convinced us that it’s safe and effective, forces companies to produce that information, that the market alone, based on history, has demonstrated they will not produce. So if we as patients and our clinicians want evidence about what is actually going to be a good option for us, we need regulators to push companies to produce those data. Otherwise, we are going to potentially be in a world where we have a lot of options, but we don’t know which of those options are good. Because we won’t have the data available to us to help inform those decisions.
DG: Final question, Holly. You’ve been having conversations about drugs and prices and access for probably about 15 years now. As a result of the approval of Aduhelm, are people having different conversations? The people you talk to — these insiders, these wonks, these drugmakers, these policy folks.
HFL: I think we’re seeing a real glimmer that something might actually change politically. This is not necessarily like a win-win circumstance, like there are going to be people who feel like they are losing out in these scenarios. And it’s challenging to think about from a policy perspective that we have to make standards that apply to whole populations and the whole pharmaceutical industry. There are patients who have desperately unmet treatment needs. But I would say that the way to address their challenges is not to reduce the evidentiary requirements, because what we want are drugs that work, not just drugs.
DG: Holly, thank you so much for taking the time to talk to us on Tradeoffs.
HFL: Yeah, my pleasure. Thanks for having me.
DG: There’s one more big question facing CMS about Aduhelm.
Biogen’s $56,000 a year price tag pushed Medicare to hike premiums of Part B, which covers drugs like Aduhelm that are administered in a doctor’s office, by about 15% — way more than normal.
But now that Biogen has cut the price almost in half and CMS has limited its coverage, the agency is considering lowering premiums.
A decision could come any day.
I’m Dan Gorenstein, this is Tradeoffs.
Tradeoffs’ coverage of health care costs is supported, in part, by Arnold Ventures and West Health.
Want more Tradeoffs? Sign up for our weekly newsletter!
Additional Research and Reporting on Aduhelm and Medicare’s Decision:
Will Biogen sue Medicare over its restrictions on the Alzheimer’s drug, Aduhelm? And other big legal questions about the decision (Nicholas Florko, STAT, 4/12/2022)
Medicare Officially Limits Coverage of Aduhelm to Patients in Clinical Trials (Pam Belluck, New York Times, 4/7/2022)
Califf admits controversy over FDA’s Alzheimer’s drug decision impacted experts’ trust in the agency (Nicholas Florko, STAT, 3/31/2022)
Medicare premiums could decrease ‘soon,’ after decision on Alzheimer’s drug Aduhelm (Rachel Cohrs, STAT, 3/17/2022)
Accelerated approval reforms take center stage at House hearing, but a way forward remains unclear (Zachary Brennan, Endpoints News, 3/17/2022)
Alzheimer’s patient groups pressure U.S. to pay for Biogen drug (Deena Beasley, Reuters, 3/13/2022)
Medicare’s Unprecedented Alzheimer’s Drug Decision (Tradeoffs, 1/20/2022)
FDA allows drugs without proven clinical benefit to languish for years on accelerated pathway (Elisabeth Mahase, BMJ, 7/30/2021)
The Aducanumab Aftermath (Tradeoffs, 6/22/2021)
Phil Gutis, Alzheimer’s patient and advocate
Holly Fernandez Lynch, JD, MBe, John Russell Dickson, MD Presidential Assistant Professor of Medical Ethics, University of Pennsylvania
The Tradeoffs theme song was composed by Ty Citerman, with additional music this episode by Blue Dot Sessions and Epidemic Sound.
This episode was produced by Ryan Levi and mixed by Andrew Parrella.
Special thanks to Ameet Sarpatwari.
Additional thanks to Sean Dickson, the Tradeoffs Advisory Board…
…and our stellar staff!