Dan Gorenstein: Last June, Alzheimer’s patients and advocates rejoiced. 

News clips: This morning, a historic development in the fight against Alzheimer’s. // It’s something that will help the quality of life. // We have hope on the horizon. // The FDA approving a new treatment for the condition for the first time in nearly 20 years. 

DG: But would Medicare, which insures almost everyone who has Alzheimer’s, pay for the $56,000 drug Aduhelm?

CMS Meeting: Good afternoon…

DG: For the past six months….

CMS Meeting: And welcome to the National Coverage Determination listening session…

DG: ...the Centers for Medicare and Medicaid Services met with stakeholders…

CMS Meeting: I am the chief science officer for the Alzheimer’s Association // Professor of neurology at Brown Medical School…

DG: …reviewed controversial clinical trial data…

CMS Meeting: And I’m the chief medical officer at Biogen // I’m the chairman and co-founder of US Against Alzheimer’s…

DG: And finally, last week, the agency delivered a surprising preliminary verdict: Only a tiny sliver of the 1 million plus Americans with early Alzheimer’s would get the drug covered.

Today, we talk with a patient, a doctor and a former federal official about the decision’s potential wide-ranging ramifications.

From the studio at the Leonard Davis Institute at the University of Pennsylvania, I’m Dan Gorenstein, and this is Tradeoffs.

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Sean Tunis: I was working at my desk at home and somebody texted and said, “Oh, I’ve heard a rumor that they’re going to put this online a day earlier than the due date.”

DG: Sean Tunis spent six years as the chief medical officer of the Centers for Medicare and Medicaid Services, or CMS, the federal agency that oversees Medicare.

He’s also advised the FDA, Alzheimer’s advocates and the drugmaker Biogen.

ST: And pretty soon after that, I checked on the CMS website and sure enough, the policy had been posted. 

DG: And what did you think?

ST: So, you know, I was certainly expecting that Medicare would be likely to restrict, in some way, the coverage of the drug.

DG: Sean explains that it’s common for Medicare to only cover a drug for people with certain symptoms or diagnoses. In this case, the drug showed some potential benefit only for people with early onset Alzheimer’s — just a subset of the 6 million Americans who have the disease. 

Medicare also sometimes requires companies to collect data about individual patients, too. But that’s not what Medicare did here.

ST: What I wasn’t expecting was the requirement that patients would be participating in randomized clinical trials as a requirement for Medicare to pay for the drug. This just did not follow anything that looked like a precedent that I was familiar with.

DG: Medicare took this to a whole new level, blocking access to an FDA approved drug for virtually all patients except those willing to enroll in a clinical trial, essentially saying we don’t share the FDA’s confidence in this drug’s clinical data. We want another round of clinical trials to better understand the drug’s risks and benefits. 

So Sean, Medicare has never done this before. There was zero precedents. When you were reading this at your desk at home, what was going on in your head?

ST: It made me a little anxious just because in some ways, I, it struck me immediately that this was going to have a lot of ripples for quite a while. Like this, you know, this was a big deal.

DG: This decision is a big deal, in part, because it impacts more than just this one drug. Aduhelm is the first in a pipeline of promising treatments for this devastating disease that impacts millions, and that pipeline, could be worth billions to pharmaceutical companies.

Sean, how do you think we got here?  Like why did CMS seem to go so far off script?

ST: I’m not thinking of quite the right metaphor here, you know … it’s like maybe, like, the perfect storm, you know what I mean? 

DG: You took the words out of my mouth.

ST: Right it’s, you know, the perfect storm, right, was like three storm systems that should never have come together and all of a sudden you’ve got a superstorm and that’s kind of feels like what’s going on here. Everybody’s terrified of this disease. There hasn’t been a new drug in 17 years. And something comes along that, you know, offers some hope and then in the middle of that, you kind of spark anxiety about unreasonable drug prices. All of that is, you know, pieces of the perfect storm.

DG: You mention unreasonable drug prices, and of course, Medicare can’t negotiate drug prices and is also forbidden from considering cost in coverage decisions.

But I gotta wonder, you know, how much Biogen’s $56,000 price tag play in creating this situation.

ST: You know, all of this happened in the context of the debates about whether Medicare should have the authority to negotiate drug prices, right? And here you have a drug that’s enormously expensive with at best debatable evidence — and, even if you believe the evidence, you know, a likely small benefit. And it comes in at $56,000 a year, and everybody looks at that and they go, what is wrong with this picture? That just, like, it just doesn’t make sense that Medicare — if they decided to cover this — would actually have to pay that amount. So I’m not saying that’s entirely because of the economic burden, but it’s the economic burden combined with multiple lines of concern and, kind of, unresolved policy that sort of exploded in this, you know, in the context of this decision.

DG: So, assuming this initial decision sticks, I’d like us to talk about the fallout for a few of the stakeholders.

Let’s start, Sean, with the federal agencies where you used to work — CMS and the FDA — what ripple effects, do you think, might this decision have on those institutions?

ST: Certainly at least at a high level, it really looked like there were these two big agencies who looked at the same clinical trial data and came to different conclusions about, you know, what it meant. One thing that strikes me as fairly straightforward that should have happened in this case is a lot more conversation between FDA and CMS before the approval ever happened. But to my knowledge there was little or none. And that seems a little bit inexcusable. 

DG: Right … basically we’ve built up a system where doctors, patients and drug companies expect that if FDA approves a drug, Medicare covers that drug. This ruling throws that up into the air and now we’ve got a bunch of questions.

Like what does this mean for private insurers like Blue Cross, United and Aetna? 

A few health plans, we know, came out last fall saying they wouldn’t cover this drug, but a bunch were waiting to follow Medicare’s lead. Where does this leave them, Sean? 

ST: I think the payers, in general, have been feeling for some number of years that the FDA approval standards have been, you know, have been kind of moving in a downward direction in terms of how stringent the evidence requirements have been. And, I think the payers are kind of relieved and also a little bit reassured that some sanity exists in the system and that even when the FDA makes a controversial call, that there are still policy mechanisms in place to give that a second look.

DG: Quick aside: Medicaid, the insurance program for low-income Americans, is still required to cover Aduhelm for all eligible patients. And even though Biogen recently slashed the drug’s price to $28,000, states are worried this could hit their budgets hard. 

So finally, Sean, what are the pros and cons of this decision for the pharmaceutical industry?

ST: Obviously for Biogen, this is a nightmare. For other companies that have drugs in the pipeline, this kind of changes the landscape for them in terms of maybe deciding that they need to actually show direct evidence of clinical benefit. And then, it’s also kind of a bit shocking and concerning, again because, Medicare has sent a message here that they are willing to exercise independent authority that does not defer as much as they historically have to FDA decision-making.

DG: Sean added that he guesses this new trial process could take three to five years, involve a few thousand patients and cost Medicare hundreds of millions of dollars.  

After the break, we head to Raleigh, North Carolina to hear from a patient and Stanford, California to talk with a doctor who is not giving up hope. 

MIDROLL

DG: Welcome back.

On today’s show, we’re breaking down an unprecedented move to severely restrict coverage of Aduhelm, sometimes called aducanumab, the first new Alzheimer’s drug in nearly 20 years.

Citing insufficient data on the drug’s safety and efficacy, Medicare is proposing to only pay for patients who enroll in additional clinical trials.

While some patients worry about the side effects, like brain swelling and brain bleeding, others like 60-year-old Jay Reinstein were on the edge of their seats… 

Jay Reinstein: This drug was perfect for me because I’m early stage, I’m doing pretty well and I had so much hope.

DG: Early onset Alzheimer’s forced Jay to retire at 58 after a 20-plus year career in local government. 

He lives in Raleigh, North Carolina, and is keeping busy. He’s a radio host, an advocate and a grandfather.

Jay, how old are your grandkids? 

JR: Okay, so this is a tough one. Grandkids are 12, 9, 6, and 4. I did it. I can’t remember the names all the time … right now I’m trying to think… my grandkids, um, Zoe, Frost, which is a crazy name, uh, and I’m forgetting. I just, I’m forgetting the names really quickly here, but I’ll remember them shortly. 

DG: Jay’s days are full of daily reminders like these that his disease is on this slow, inevitable march.

JR: I know this drug is not going to cure me. It’s all about just a little bit more time. 

DG: Now, as Jay sees it, CMS has potentially slammed the door on that dream of a little more time.

JR: I mean, this was … all we have is hope, you know. We were so close to getting something. Now you’re telling us no, a clinical trial? That’s, you know, it’s, it’s bullshit. I hate to say this, but it’s like the government has given us the middle finger. 

DG: Do you plan to try to enroll in one of these Medicare trials?

JR: I mean, absolutely. I want to enroll in everything possible, but, the thing is I think the downside of the clinical trials is that I don’t know if I’m getting the drug or a, um, a placebo. To ask people now who are already so stressed out about this now you’re going to have us scramble to try to get in these clinical trials, try to find … I don’t know if you’ve ever looked … going onto these trial sites, it’s not easy. It’s very confusing. There’s all these limitations. The FDA approved the damn drug. That’s what we thought was what we needed. Now you’re putting another barrier in. So, no, I mean, I will definitely try to enroll, but I know the process is going to be very frustrating. Very frustrating.

DG: Jay’s wife has a creed: Do what you gotta do. He admits he’s not sure what that is yet. Maybe, he says, he’ll call Biogen, see if they’ll cut a deal with him. 

We’ve now heard from a patient and a policy wonk, so what about the providers — the docs and nurses with little to offer patients suffering from this devastating disease? How do they feel about this decision that starkly contradicts the FDA’s initial approval of Aduhelm? 

We head west to California to hear from not just any doctor, but one who’s spent years  enrolling patients in clinical trials for Aduhelm and other Alzheimer’s drugs.  

Sharon Sha: I was surprised, very surprised.

DG: Sharon Sha is a neurologist and associate vice chair of clinical research at Stanford University.

DG: Sharon, how did you feel on the inside when you saw the news? You said it was striking, but how did you actually feel? 

SS: Initially slightly disappointed not because I think it was the wrong decision, but I’ve been doing a lot of planning in preparing to offer this drug for our patients in a safe way. So all of that work may not have been needed had I known already that CMS was going to decide we’re not going to cover this drug outside of a clinical trial. 

DG: Do you anticipate that as a result of this CMS decision, people — you and others — will say, okay, we’re going to run a specific trial that’s going to meet the specific requirements that CMS laid out?

SS: I don’t know if there are going to be others that are going to say I’m going to write a trial, I’m going to apply for grants and run a study. I think the people who have the most vested interest in proving that this drug works are the people at Biogen, and they already have that phase four trial requirement mandated by the FDA to be performed within nine years of the approval anyway and so they would just need to follow those stipulations that CMS has put forth for it.

DG: Okay, to be clear: you’re saying if this CMS decision stands, you expect Biogen to try to basically kill two birds with one stone, right? Tweak the extra trial they already had to run for the FDA and make sure it meets these new CMS requirements.

In terms of those requirements, Sharon, one big shortcoming of the original Biogen trials was their lack of diversity. Public data show nearly, I think, 80% of participants were white even though the risk of Alzheimer’s disease is much higher for Black and Hispanic patients.

Now CMS says it’ll only consider trials that are representative of the national population diagnosed with the disease. So, how hard is it to meet that diversity bar?

SS: These clinical trials take a lot of time and resources. So usually, people who have to do their jobs, can’t take time off, cannot participate in a clinical trial because they can’t afford it. And those tend to be people in underserved communities. So it can make it very hard to be as diverse. So we have to think about not only Biogen’s responsibility but we as a community, as a scientific community, as a society, how do we support research like this?

DG: So obviously, as you know, this decision is not final. CMS is accepting public comments over the next month, Sharon. If you had CMS’s ear right now, what would you tell them to change, if anything, about this decision?

SS: It’d be great if they thought about covering additional tests, such as an amyloid PET scan, to really confirm whether or not we’re giving the drug to the right patients and whether or not to continue giving the drug and see if it’s working for them.

DG: So that would be the one comment you would make?

SS: That’s the one comment that I would make thus far.

DG: I guess I’m surprised. I would’ve thought that another comment you would make to CMS is that CMS should just cover the drug.

SS: No, I mean, I think, I don’t think that even though I may have said I was initially disappointed because of the work that I’ve put in and the, you know, the heartbreak that patients might be going through, the trial was messy from the outset … the data, the diversity … and so this is CMS’s answer. It’s a chance to redo the trial. It’s forcing Biogen’s hand to redo the trial. 

DG: Sort of the final question here, Sharon. When you’re 66, right, 20 years out from today, what’s the legacy of this whole saga going to have been?

SS: I think a lot of people said when the FDA approved this drug, we’ve done it. The very first disease modifying drug for Alzheimer’s disease is here. It’s now. And even if it’s not perfect, the ones that follow might even be better. It’s a wave of drugs. And in the past, when we said to my Alzheimer’s patients, we don’t have anything for you … you know, we now have something. So that could be part of that disappointment with CMS denying coverage, but it grounds us to say, you know what, we need to be sure. So that we can really say to this patient in front of me, I have something for you and I think it’s gonna work.

DG: And in that way, that’s why you think the CMS decision was a good decision.

SS: Yeah.

DG: Because they’re demanding that.

SS: Yes, exactly. They’re demanding that we have proof. So when I say to my patient, “I have a drug for you. It’s going to help you,” that I can say that with confidence … but I still think you know, I think … we all have hope. And that’s what we’re all working for. I don’t know why I’m getting so emotional. We’re all hopeful.

DG: Why are you getting emotional?

SS: The patients that I see are going through a lot. The families are going through so much. And the time that I say to them, “You have Alzheimer’s disease. We don’t have a cure for you right now, but I’m working on it. We have experiments, we have trials,” and those that enroll, they are hopeful and I never want to take away that hope. So the CMS decision, I think, might take away hope for those patients. And I want everyone listening and reading this decision to know that we’re not giving up. It doesn’t mean that we don’t have a drug for you. It means that we just need to be better about proving the drug works for you and we’re going to get there. So I don’t know what the future brings, but when I’m there, I want to look back and say, yes, this was messy, but we got to something and we demanded that it was proven, safe and helpful for you.

DG: Sharon, it has been an absolute honor and privilege to talk to you. Thanks for taking the time to talk to us on Tradeoffs.

SS: Man, you got me. [Sniffles and laughs]

DG: Since the CMS draft decision came out on January 11th, nearly 200 public comments have come in. The comment period closes in February, with a final decision expected in April. 

Sean Tunis anticipates a full court press — possibly even legal challenges — from patient advocates and drugmakers, who have called the decision “discriminatory” and “dangerous.”

ST: One of the things that I learned when I was working at CMS is, you know, regulated industries don’t respond well to surprises. When you do something for the first time and you haven’t even given people kind of a heads up that it’s something that is on the table, it never goes down very well. 

DG: Sean added it is not uncommon for draft decisions to change dramatically. 

I’m Dan Gorenstein and this is Tradeoffs.