Caleb Alexander: I don’t think this is a tough call…I mean, we are not sitting right on the fence. I can assure you that.

Dan Gorenstein: Johns Hopkins professor Caleb Alexander and nine other members of a Food and Drug Administration’s advisory panel unanimously opposed approving a controversial new Alzheimer’s drug.

CA: The evidence simply isn’t there at this time for this product

DG: But, on June 7th…the federal agency dropped a bomb.

News montage: Major news out of the FDA today on what could be a potential blockbuster // The first new treatment for Alzheimer’s in nearly two decades // What some are calling potentially the biggest drug of all time 

DG: Ignoring the shaky science and their advisers, the FDA approved aducanumab, now known as Aduhelm.

Hours later, drugmaker Biogen slapped a $56,000 a year price tag on it.

Some patient advocacy groups rejoiced. 

Patient montage: The Alzheimer’s Association has been waiting decades for this. // It just gives us so much hope // That’s all I asked for, just a little more time 

DG: Aducanumab’s approval is sending shockwaves through the U.S. health care system.

So this week, we’re bringing you a special series, four conversations with people asking messy, difficult questions and reckoning with this moment.

Today, part 1: the doctor.

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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Winston Chiong: I’m Winston Chiong. I’m a neurologist and an ethicist at the University of California, San Francisco. My main expertise is actually not in clinical trials or an FDA. It’s just in decision-making and in how to communicate complex information to patients and families. 

DG: How long have you been a doc? 

WC: Hold on. I’ll have to check my CV. I’ve been in dementia either in training or since then as faculty, since 2010. 

DG: What would you say, like, sort of generally, Winston, what kind of patients are you seeing and how would you characterize your practice?

WC: So one thing that we do have particular expertise in at UCSF is in non-Alzheimer’s dementia, but I do see a lot of just your everyday garden variety Alzheimer’s disease as well. Certainly a lot of my patients begin with mild memory symptoms, misplacing objects, getting lost, repeating themselves in conversation. As we know, it’s a progressive illness. So as the disease continues, people begin having more difficulties with everyday activities, which could include simple things like feeding themselves, dressing themselves, using the toilet, taking a shower, things like that. And those are things that are very burdensome also for caregivers and families.

DG:  Winston, do you have any patients in your panel right now that you would consider prescribing aducanumab to?

WC: So I have a patient coming in next week. And, this is a patient who would meet the enrollment criteria for the study. So this is somebody with very mild Alzheimer’s disease. This is sort of the perfect patient if there is one for this drug. And, even in this patient, I would not recommend that they take the drug, but I would want to listen to, you know, their values, what risks they’re willing to consider and, think with them together about whether it would make sense for them.

DG: Winston makes it clear that he won’t even consider prescribing aducanumab right now to anyone other than patients with very mild cognitive problems…the people the drug was tested on in the trials…even though the FDA’s approval left the door open for doctors to prescribe the drug to pretty much anyone with any stage of Alzheimer’s.

When you meet with this patient of yours next week, Winston, how will you describe, or how would you explain the risks and the benefits specifically knowing this patient’s case? 

WC: For me, one thing that drives my thinking a lot is that when the FDA was considering this drug, they put together this expert panel as they always do. And this panel was unanimous that the company had not shown that the drug was beneficial. And I think that’s an important place to start. And, more specifically, thinking about this patient’s case…we’d start by talking about what are the potential benefits of the drug. So, we have these old drugs, these cholinesterase inhibitors like donepezil that we’ve been using for 20 years that nobody’s very impressed by. And even in one of the two studies for aducanumab that seemed to show a positive benefit, the benefit was smaller than the benefit that we see with donepezil, and those drugs have much, much fewer risks. And so, yeah, it’s conceivable that a given patient might have a delay of certain negative outcomes by a few months, but it is just as conceivable, that that patient is going to have one of these really significant side effects.

DG: After the break, Winston walks us through those side effects, from brain swelling to big insurance bills…and the longer term impact this approval could have.

[MIDROLL]

DG: Welcome back. 

This is part 1 of our special conversation series with people reckoning with the FDA’s recent approval of a controversial and pricey new Alzheimer’s drug.

Today we’re talking with neurologist Winston Chiong, who’s walking us through how he’ll be discussing the drug’s risks and benefits with interested patients. 

So Winston, before the break, you were telling us you’d caution your patients that it’s very likely the drug’s side effects may outweigh its small benefit. What are those potential side effects?

WC: Sure, about 40% of people in the trials who got the full dose of drug had brain swelling or brain hemorrhage. Most of the time this is something that we just caught on scans, but about 10% of people did have symptomatic headache, nausea, vomiting, confusion, vision changes. These were significant enough in a reasonable proportion that they had to be pulled out of the study. This is also in kind of an ideal clinical trial setting. I think a lot of us have many concerns about whether the risks would be greater in a clinical population that’s not as closely monitored.

DG: Is brain swelling and brain hemorrhaging a significant risk? Are these big problems or are these just like nausea but for your brain, you know what I mean? Like you get nauseous, it doesn’t feel good, but like you get over it.

WC: In most cases in the trial, they paused the drug when they saw this and it went away, but there was about like one in 14 participants in the trial that had to be permanently removed from the trial. These trials are usually pretty conservative about excluding people so, you know, it might be a much smaller group of people that really has to stop the drug. So I wouldn’t be so scared of these risks that I consider them unacceptable if there was the prospect of a big benefit on the other side.

DG: According to a recent Kaiser Family Foundation report, some patients on Medicare could be on the hook for as much as $11,000 out of pocket every year for this drug.

Do you think, Winston, that you’d bring up the costs, the financial cost, the financial toxicity potentially for patients?

WC: Yeah, I think that’s a really tough question to bring into the room. For me, cost is a little bit secondary in that you know, Alzheimer’s disease is a tremendously costly disease. It has such huge impacts, not just on the healthcare system, but also on patients and families. You know, people want to do everything they can, you know, and so, if we had a $60,000 a year drug that really worked, I think that could be worth it. So in that sense, I would prefer to focus, when I’m talking with patients and families on what I think the main problem is, which is just that the drug doesn’t seem to help a whole lot.

DG: Biogen has listed the price for aducanumab at $56,000 a year. That does not include MRIs or additional out-of-pocket costs that might come with it. If you, Winston, were in charge of Medicare and had $56,000 to spend every year on every patient with early onset Alzheimer’s or at high risk of it, what would you spend $56,000 on?

WC: Wow. That would be amazing to think about the things that we could do with those sorts of funds. I think that probably the biggest burden that we see is the caregiving burden. So people have falls, people have undiagnosed infections, other things that lead to worsening of their Alzheimer’s disease because their caregivers don’t have enough support. So, if we could pay caregivers, a living wage, invest in community supports like, you know, day programs or respite programs that give caregivers a break, these are things that, would prevent some of the other bad medical outcomes that that hasten progression.

DG: As a doc, I’m curious how you think about the FDA on a day-to-day basis and whether or not this approval changes your perception of the FDA. 

WC: I think that in this country, we’ve been fortunate in not having to think a lot about the FDA on a day-to-day basis. I definitely couldn’t stand here and say that everything they’ve done to this point has been right, but there’s been a real benefit for clinicians and patients. And, it is a really big burden to be having these individual conversations with patients and families where a lot of the things that we would ordinarily take as cues that the drug is beneficial — I’d include the FDA and the endorsement of the Alzheimer’s Association, honestly — are not for us really reliable cues anymore. I think this is something where it’s really going to force us clinicians, but particularly patients and family members, to dig in and try to evaluate complex data that really, we ought to be able to rely upon these regulatory agencies, these guardians to be looking out for us. 

DG: Since the ruling has come out from the FDA, what are conversations like between doctors who are treating patients with cognitive problems?

WC: I think that overall we’ve been quite disappointed. I think a lot of us are very worried about what this means for both drug approvals down the line in terms of, you know, has this lowered the bar for the next set of treatments? And also what does this mean for research? If we have this drug that’s been approved and people can get, but we don’t know whether it works, then how are we even going to study the next drug in terms of, are we going to be comparing it to this drug? Are we going to be able to enroll patients in clinical trials If they’re taking this drug? So, I think as someone who I believe that the way forward for patients is by doing better science this has been a bad week for good science in my view.

DG: Winston, thanks a lot for taking the time to talk to us on Tradeoffs.

WC: Thank you. It’s been great to have this conversation.

DG: We caught up with Winston a few days after this interview.

He told us the patient who might have been a good candidate for Aduhelm decided not to take the drug after they talked through its risks and benefits.

In several appointments, talk of Aduhelm left little time for Winston and his patients to discuss other priorities like support groups for caregivers and end-of-life planning. 

Finally, Winston’s also joined a work group at the American Academy of Neurology to develop recommendations on prescribing, patient safety and insurance coverage for Aduhelm.

I’m Dan Gorenstein and this is Tradeoffs.