'Some Hope Is Better Than Having No Hope'

[0] From New York Times, I'm Michael Bavarro.

[1] This is a daily.

[2] Today.

[3] The FDA recently shocked the world of medicine when it approved a treatment for Alzheimer's, despite a fierce debate over whether the drug actually works.

[4] I spoke with my colleague, Pam Belloc, about the story behind that approval and where exactly it leaves Alzheimer's patients and their families.

[5] It's Wednesday, July 7th.

[6] I was at a talk one time, and they were explaining to us what Alzheimer's is like.

[7] And they were saying, think of it as like you're going to a clerk at a desk who has some files, and you go to them and you say, I need the file about X. And they go and they open up the drawer and they pull out the file.

[8] they bring it to you.

[9] And that's just the way the brain works, you know, when you're trying to remember something.

[10] And then normal aging is, now the clerk's really old, and so it takes that person a while to walk over.

[11] They, you know, they have to figure out which cabinet it's in.

[12] They finally find the folder, and they bring it over to you.

[13] But, you know, you get it eventually.

[14] And Alzheimer's is you go over to the file cabinet.

[15] You open up the drawer, and there's hardly any files in there.

[16] I mean, they're just not there.

[17] And so there's nothing to grab.

[18] Wait, I see them there.

[19] You are muted.

[20] You can't hear me?

[21] No, I can hear you.

[22] We can't hear Debbie.

[23] Debbie and Susan, we can hear.

[24] Oh, we have to unmute.

[25] Oh, there are.

[26] Hey.

[27] Pam, tell me about this couple that you just interviewed.

[28] So Debbie Rosencrantz and Susan Waski, they are a married couple.

[29] So if you want us to identify ourselves, if it gets confusing.

[30] Yeah, yeah, yeah.

[31] Who is that?

[32] Who's that talking?

[33] Just so we know.

[34] That's Susan.

[35] And this is Debbie.

[36] They live in Cambridge, Massachusetts.

[37] They're in their late 60s, and they have been together since shortly after college.

[38] You know, around that time, we both came out as lesbians.

[39] And it was a small lesbian community.

[40] So everybody knew everybody at the time we were cute.

[41] Now we're a little old for that, but, yeah.

[42] So, like, who asked who out first?

[43] I asked her out, but she didn't actually know it was a date.

[44] I thought it was a date, but she didn't think, she thought we were just going to the movies or something.

[45] I feel from interviewing them, I've got a sense of a very strong, very trusting relationship.

[46] and I just found them to be both very, very thoughtful and very warm.

[47] I think one of the things in the beginning is because it was like early women's movement stuff and people were just angry all the time and I think that was very wearing.

[48] And with Susan is that she just, she wasn't angry all the time.

[49] And we could still get things done and feel like we were being productive.

[50] And that definitely appealed to me. She also took me to really good movies.

[51] And that was the poor.

[52] What was your favorite?

[53] Do you remember?

[54] I do.

[55] It has Meryl Streep in it, I think.

[56] And it's the one where there's the one where we saw at the movie theater in when we could, there was a snowstorm where there was, this is what happens to my brain now.

[57] It just sort of melts.

[58] We couldn't get a seat.

[59] You know what you want to mean?

[60] One of the first times Debbie noticed that something seemed off with her memory was at work.

[61] She would have counseling sessions as a social worker with patients.

[62] And she was very accustomed to just remembering everything that happened and then writing it down later.

[63] And she started to feel like she couldn't remember what was happening.

[64] My memory was the one thing I could really depend on.

[65] was not being dependable.

[66] I just had been taught to memorize things always, and that had worked for me. And then all of a sudden, it stopped working for me. And the place I felt it the most was in my clinical work as a social worker.

[67] Like, I used to be able to remember something.

[68] Well, wasn't it four and a half years ago that you just like some such happen?

[69] I could remember, and I no longer had access to that type of memory.

[70] And I could feel myself not catching what was being said in sessions.

[71] And so I knew something was wrong.

[72] She had to take notes very incrementally because she couldn't actually remember what had happened in the session after it was over, and that was really troubling for her.

[73] And how did her wife, Susan, make sense of this?

[74] I think at first, actually, Susan, kind of chalked it up to normal aging.

[75] A lot of what she, and probably even I did in the beginning, was, oh, you know, it's okay.

[76] you know, you're, you're, that's just getting old, you know, that's the common refrain.

[77] It's just aging.

[78] Everybody can't remember so -and -so's name.

[79] But then, you know, gradually Susan started to notice things.

[80] What was the first thing that you were calling out?

[81] You know, probably one of the first times where I really could see that was we would take the statements from the bank and put them in the a notebook.

[82] And Debbie was trying to take these statements and put them in chronological order and then put them in a notebook.

[83] And she just couldn't do it.

[84] And it was sort of like, wow, it was just really mind -blowing to me that that was just too difficult.

[85] And once she started seeing it, she could see examples everywhere.

[86] Some of them...

[87] I think we did have chicken pop -pie one time without chicken in it.

[88] Or lighter moments, things that would make them laugh, like cooking problems or...

[89] The dog would get fed repetitively.

[90] Challenges feeding the dog.

[91] We were feeding the dog.

[92] How often?

[93] Not we.

[94] I was.

[95] But behind the lighter moments, Debbie had the sense that parts of her memory were just fading away.

[96] I think it's like seeing something and thinking I am going to understand it.

[97] and then I go to grasp it, and it dissipates as I grasp it.

[98] And so then I go, oh, oh, no, I need to go over there and get it.

[99] And I go to go get it over there.

[100] And as I get closer to grasp it, it dissipates as I grasp it, and it's just continuously happening.

[101] It's frustrating.

[102] She went to a number of different doctors, and ultimately, about three years ago, she received a diagnosis.

[103] And how did she take the news?

[104] It was devastating.

[105] I actually think it felt like being punched in the stomach.

[106] You know, she knew a lot about what to expect because her mother had had dementia.

[107] And I had seen, when my mom was an assistive living, I had seen people who passed away from it, and it was not like a, it was a difficult death.

[108] And so she knew that what lay ahead was that she would gradually lose her memory.

[109] She would ultimately stop being able to recognize Susan and her own daughters.

[110] I worry about both the impact of my disease on my family and Susan and our kids.

[111] And I also worry about whether I've handed it.

[112] down, pass it on to my biological daughter.

[113] And I worry about like where there are times that just where people are having trouble with swallowing or some of the more advanced aspects of Alzheimer's that I just don't even, I think that I have used my brain to edit certain situations that are too painful to go into.

[114] Like I say it now, but I don't generally let my brain go there.

[115] And she knew that Alzheimer's is a disease where eventually her brain would be so diminished that basic functions like being able to swallow would be stolen from her.

[116] Right.

[117] But there have to be some kind of treatments, right?

[118] Well, unfortunately, Alzheimer's is one of those illnesses that there really are very few options for at the moment and it affects an awful lot of people, maybe six million Americans at the moment and there just are not any treatments that can do more than maybe slow down memory decline for a matter of months and each of those stops working at some point, and none of them stop the disease, none of them reverse it, nobody gets better, and there is no cure.

[119] My understanding was that there was no option available.

[120] But one day, she bumps into a friend of her mother's at a hospital, and the friend tells her that there's a new drug that's being tested, for people with Alzheimer's, and that there's a clinical trial, and she might be able to sign up and see if she can be treated with that drug and see if it may help her.

[121] How did you feel when you heard about the research, when you heard about the trial, were you nervous about it?

[122] Were you excited?

[123] And to get into the trial was just a lucky moment for me. So she signs up.

[124] And for her, that's very exciting.

[125] It gives her a sense of hope at a time when she was really losing a lot of hope.

[126] In fact, one of the television stations did this little tape of us.

[127] And I think I'm like practically skipping down the street.

[128] I'm so excited about getting into this trial.

[129] And I thought it helped would be like a light switch type help.

[130] you were hoping for a cure.

[131] Yeah, a cure.

[132] We'll be right back.

[133] Pam, tell us the story of this drug that Debbie ends up being enrolled in a clinical trial for.

[134] So a few years before Debbie would even hear of this drug, it starts to take the Alzheimer's community by storm in 2015.

[135] Tonight, people with Alzheimer's and those who care for them are lords.

[136] about an experimental drug that could change the way we look at this disease.

[137] When Biogen, this company in Massachusetts, presented very preliminary results that seemed somewhat promising.

[138] Early tests show its drug could reduce the presence of plaques in the brain believed to be responsible for the onset of Alzheimer's.

[139] You know, we're talking about a field where people have been trying desperately for years.

[140] to find something that works for Alzheimer's.

[141] For more than 5 million Americans living with Alzheimer's, there's nothing, no drugs, no therapies, to stop or even slow down the disease from erasing their memories.

[142] And at that point, there had not been a new drug approved for Alzheimer's for about a dozen years.

[143] So in that context, even somewhat promising results are pretty exciting.

[144] Absolutely.

[145] It's showing some early promise, but the key word there is early.

[146] One of the really exciting things about this drug is that it attacks one part of kind of the underlying biology of the disease.

[147] Alzheimer's, it's a very complex disease, and there are several things that happen in the brains of people who have the disease.

[148] And one of them is that there's a buildup in the brain of this protein called amyloid.

[149] and the brain in people with Alzheimer's, it can't clear out that protein.

[150] It can't get rid of it in a normal way.

[151] And so what happens is it accumulates and it clumps into plaques.

[152] And so this drug called aducanamab, what it does is it goes after those plaques.

[153] It basically breaks them up.

[154] And it does this more effectively than previous drugs that have been tried.

[155] And the hope is that if you use it early enough in the progression of Alzheimer's disease, that it might have a meaningful effect, that it might be able to slow down the cognitive decline that people experience.

[156] And because of how promising this data seems, the FDA decides to fast -track the development of this drug.

[157] It says, okay, you've done your phase one trials.

[158] Now you can just skip ahead, skip phase two, and you're going to do the last phase of clinical trials, which is called phase three.

[159] So the FDA thinks there's a chance based on this fast track designation that this could potentially really work.

[160] I mean, that's the hope.

[161] And there are two trials happening at the same time, and Debbie becomes a participant in one of them.

[162] Do you recall, like, you know, any feeling that the drug was doing anything for you?

[163] Do you know?

[164] I mean, it can be very hard to tell.

[165] Debbie was pretty sure she was on drug and it was working.

[166] And, of course, Debbie doesn't know whether she is actually getting the drug or whether she's getting a placebo because in a randomized clinical trial, the whole point is that you don't know what you're getting.

[167] Yeah.

[168] I mean, I think I was really optimistic that there was a. drug.

[169] And so for me, it was like, yes, it's working.

[170] And I really, like, I just, I think I put my heart into it.

[171] It's working.

[172] And then one day, about eight months after Debbie has started the trial, she gets a call from a friend who tells her that the trial has been stopped.

[173] Somehow she got the news and she's like, there's in the news that they're canceling the biogen trial.

[174] Is that the one you're in?

[175] And that was the first we heard of it.

[176] Because it looks like the drug is not effective and there's no point in continuing to study it.

[177] And eventually later that day, we got a call from Dr. Forrester McLean explaining what was happening and that they were, they had no idea.

[178] Everyone was completely blindsided by it.

[179] Explain that to me. how can Biogen know that the drug isn't working if the clinical trial isn't complete?

[180] Yeah, so Biogen had set up basically what's called a data safety monitoring committee that checks about halfway through the trial to see what are the trial results so far actually showing.

[181] And the committee said, we don't see any indication that this drug is helping do what it's supposed to do, is slow cognitive decline, slow the progression of memory and thinking problems in people.

[182] It doesn't seem to be doing that.

[183] It doesn't seem to be working.

[184] So there's no point in continuing and Biogen says, let's just pull a plug.

[185] So Biogen pulls the plug on both trials, the trial that Debbie's in and the other trial.

[186] That's the same.

[187] And what was Debbie and Susan's reaction to that?

[188] They feel like the rug has just been pulled out from under them.

[189] I have to say that was a really tough way to be told something like that.

[190] I felt like, oh, well, that's over.

[191] It's not going to work.

[192] I mean, I thought that this was the only option.

[193] They just had this hope, and now that hope for this drug is dashed.

[194] And so it kind of felt like being dropped like a hot potato.

[195] And, you know, it's, I know for Debbie, it was, oh, that was my hope, you know, and now I don't have my hope.

[196] What, what now?

[197] So at this point, what are the options for Debbie?

[198] Yeah, she's sort of back to square one.

[199] Mm -hmm.

[200] You know.

[201] Which is to say kind of no options.

[202] Yeah, pretty much no. options.

[203] But then seven months later in October 2019, all of us who are following the Alzheimer's field were just kind of, we are all very surprised when Biogen announces this drug has risen from the dead.

[204] We're resurrecting it because it says that it has looked at the data that has come in, it's done some additional analysis, and that it found that in one of the two trials, there was some suggestion of benefit for people who were taking the highest dose of the drug.

[205] They didn't find any benefit at all in the other trial, which was virtually identical, but Biogen said that they think that the evidence from that one trial is enough.

[206] And so they decide to go ahead and apply for FDA approval of the drug.

[207] Hmm.

[208] What a roller coaster.

[209] Yeah, it's very unusual.

[210] And I think we don't really know what to make of it at this point.

[211] I mean, you have two trials that weren't even completed.

[212] Only one of those two trials shows any suggestion of benefit, and that benefit is very slight.

[213] And the drug does cause some side effects, some of which can be serious.

[214] About 40 % of the participants in the clinical trials developed either brain swelling or brain bleeding.

[215] And while most of those cases were mild or manageable, about 6 % of people dropped out of the trial because those side effects were so serious.

[216] So I think we're just all looking at this muddled picture and wondering what to make of it and whether this drug is going to prove beneficial, whether it works at all.

[217] So what does this mean for Debbie?

[218] Well, Biogen announces that because of this slight benefit that they found at the highest dose for some people, that participants in the clinical trials, like Debbie, will have the option to start taking the drug again, working up to the highest dose.

[219] dose.

[220] How did you find out that you had a chance to receive the infusions again?

[221] They contacted us.

[222] Oh.

[223] Yeah.

[224] And did you have any hesitation about that at that point?

[225] No. And what was the sort of thought process there?

[226] Just, you know, whatever evidence we had, it seemed like she wasn't precipitously declining.

[227] So maybe it was doing something.

[228] And And let's try it again.

[229] Why not?

[230] So the trials are back on.

[231] Debbie has now rejoined the study.

[232] She knows she's getting the treatment.

[233] And the next step in the process is approval.

[234] So what happens after biogen applies to the FDA to get this drug formally approved?

[235] Well, the FDA puts together all the data and it gets presented to, an expert panel of independent scientific experts that happens in November 2020.

[236] And the advisory committee, this panel, looks at all the data.

[237] And what they see, what we have and the evidence, you've got these two nearly identical clinical trials.

[238] One seems to show a slight slowing of decline, but the other one shows nothing at all, no benefit at all.

[239] So what does this advisory panel do?

[240] So this advisory panel votes overwhelmingly that this drug is not ready to be approved.

[241] It's kind of extraordinary.

[242] It's not even close.

[243] You've got 11 people, 10 people say no, and only one person says, I'm not really sure.

[244] But nobody votes yes for this drug.

[245] And that's really unusual.

[246] And, Pam, my sense is that the FDA very rarely goes against the findings of these advisory panels.

[247] So this would seem like the end of the road for this drug.

[248] This would seem like the end of the road.

[249] It is very rare for the FDA to approve a drug when its advisory committee says don't.

[250] Mm -hmm.

[251] But...

[252] We are halted for news pending, as the FDA is set to...

[253] rule on an Alzheimer's drug.

[254] Fast forward to June 7th of this year, and there is an announcement around 11 o 'clock in the morning that, guess what?

[255] For the first time in nearly 20 years, there's an experimental drug approved now for the treatment of Alzheimer's.

[256] This drug has been approved.

[257] Hmm.

[258] The FDA giving hope to millions of Americans suffering from Alzheimer's disease with this approval.

[259] Did they explain why and how?

[260] Well, basically they say they don't know enough to know if it's going to help people, but they think it's promising enough.

[261] Back in November, a committee voted there is not enough evidence to show the drug is effective.

[262] And so how does the advisory panel of all these experts who evaluated that data and said don't approve it?

[263] How do they react to the FDA ignoring their counsel?

[264] Many of the members of the advisory committee were just very upset.

[265] A third member now of the FDA's independent advisory board has quit after the agency...

[266] And three of them actually resigned, which is incredibly unusual.

[267] One advisory member who resigned called it, quote, the worst drug approval decision in recent history.

[268] Basically, the advisory committee's point is you have these contradictory results in the clinical trials.

[269] You have some safety risk, and, you know, that's just not enough to put a drug out there in the world that people are going to use thinking it might help them.

[270] And, you know, lingering in the background of all of this is that this is a very expensive drug.

[271] The drug reportedly costs about $56 ,000 per year.

[272] Biogen has said that it's going to charge $56 ,000 a year for this drug.

[273] which is going to mark it under the name Adjuhelm.

[274] And that's not going to be the only cost.

[275] There's going to be some expense to be diagnosed to see if you actually should be getting this drug.

[276] And you're going to have regular brain scans, MRIs, that will be an additional cost because you need those to make sure that you're not having brain swelling or brain bleeding.

[277] Mm -hmm.

[278] And some on Wall Street say this could be.

[279] the biggest drug of all time, but could also lead to pushback from the U .S. government as Medicare covers so many patients with Alzheimer's.

[280] Because many of the people who are going to be taking this drug are going to be, you know, over 65, a lot of this tab is going to be paid for by Medicare, and that's the taxpayers.

[281] So a lot of people are also upset about that aspect of it.

[282] This drug is expensive, and you may end up putting folks on this really expensive drug that does nothing for them.

[283] Right.

[284] The critique being that there's little evidence that this drug actually slows the cognitive decline of those with Alzheimer's, and yet it may end up costing taxpayers a ton of money.

[285] Exactly.

[286] So it's tempting, Pam, to wonder if something perhaps a bit suspicious is going on here, given.

[287] this astonishingly high cost of the drug and the money presumably to be made from it.

[288] So how does the FDA respond to all this, respond to these panelists quitting and the critique that this approval just doesn't make sense?

[289] Yeah, so the FDA says we get it that the evidence is not strong enough here.

[290] And in fact, we are not giving this our standard approval because it doesn't meet those standards.

[291] But we're going to approve it under a special program, and we're going to say that we think that down the line that is going to show that it helps people's memory and thinking problems.

[292] Hmm, kind of a Hail Mary approval.

[293] I guess so.

[294] You know, the FDA says very clearly that it is taking into account the desperation of people with Alzheimer's disease in their family.

[295] and the fact that there really isn't much else out there.

[296] And so that's one of the things that it's acknowledging here that we're putting something out there for a disease where there isn't much, even though we can't say 100 % that it is going to help.

[297] Right.

[298] And under the hope, essentially, that it will work.

[299] Yeah.

[300] I mean, if you are, a patient with Alzheimer's or you have a family member who has Alzheimer's and you hear that the FDA has just approved something new, there's a very strong chance that you're going to go and ask your doctor for that new thing.

[301] And the doctors I've talked to, many of them, are really concerned that patients will be so hopeful that the facts about how little is actually known about this drug won't really come through to them.

[302] One doctor I talked to said that he sat down with a patient and her husband, and he explained all of the concerns that he had, and they didn't hear a word about the concerns.

[303] All they heard was that there might be some benefit.

[304] So how are Debbie and Susan thinking about all this?

[305] Well, if you consider where Debbie and Susan are in their journey right now, Debbie is continuing to struggle and continuing to decline.

[306] It's been really hard to accept it.

[307] I haven't figured I'd how to manage not having a good memory.

[308] Like sometimes I keep notes, but then I forget that I kept them or it doesn't work.

[309] It's not the same as having a memory.

[310] There isn't, there isn't any substitute.

[311] She can't really contribute to decisions that the two of them need to make.

[312] And Susan kind of sees her partner slipping away.

[313] It's really tough to lose your equal partner.

[314] Basically, I have had to take over a lot of those things that were part of her agency, driving, shopping, cooking, all those things.

[315] I resisted, to some extent, I resisted that for a while because I didn't want it to be true.

[316] You know, I didn't want to have to be thinking about making decisions for Debbie about what she could and couldn't do.

[317] It does feel like death by a thousand cuts, you know.

[318] It's just these little things that go away.

[319] And it's kind of like watching a picture get fade with time.

[320] And the outline just, it's not as clear.

[321] And that's whether it's who Debbie is as a person or what our relationship is.

[322] It just keeps, it's a constant change.

[323] They are feeling very desperate.

[324] it and just kind of watching all of this unfold.

[325] Well, just this morning, she was just saying, I feel so much more confused about everything, you know, and just, you know, feeling her despondency about that.

[326] I don't remember that.

[327] Yeah.

[328] I mean, that's the harder part for me, really.

[329] What was happening this morning that made you feel despondent, Debbie?

[330] Do you remember?

[331] I don't know.

[332] You were just saying I just feel so much more confused.

[333] And because of how desperate they are, even though they understand very well that the scientific evidence for this is very iffy.

[334] And even though in the nine months or so that Debbie has been back on the drug, they have seen no benefit for her at all.

[335] They are still glad to have access to this drug.

[336] And in their view, the choice is either take something on the hope that it might eventually help her or not have a chance to take anything new at all.

[337] Right.

[338] And surrender to this disease.

[339] Yeah.

[340] And so they kind of perfectly embody the tension in the controversy over this drug.

[341] Would you guys advise people or would you have any hesitation if, you know, this thing just came out and they hadn't tried it yet?

[342] Would you say, you know what, go for it?

[343] It's the only thing out there.

[344] Or would you say, you know, given the possibility, safety risks given the kind of limited benefit and we don't even know if there is benefit maybe not like what would you say to people well Debbie I let Debbie answer first would you advise people in your support group if they could access the drug to use it yeah I would and I would even though I'm not convinced and of its healing powers but I I having some hope is better than having no hope in a significant way for me. I'm still enjoying as much of my life as I can right now, and I'm not really ready to hang it up.

[345] Pam, as always, thank you.

[346] Thank you.

[347] We'll be right back.

[348] Here's what else you need to Notre Day.

[349] The death toll at the collapsed tower in Florida rose dramatically on Tuesday after the demolition of the entire complex opened up new ways for rescue workers to search the debris.

[350] Workers have found 12 more bodies bringing the confirmed death toll to 36.

[351] More than 100 people remain missing.

[352] And, in the closely watched race for mayor of New York City, Eric Adams, a former police captain and the Brooklyn Borough president, emerged as the Democratic nominee on Tuesday night and is now all but assured to win the general election this fall.

[353] If so, he would become the city's second black mayor.

[354] Adams' victory, fueled by a rise in gun violence and Adams' pro -police message, signaled a rejection by the city's Democratic voters of calls to defund the police.

[355] Today's episode was produced by Robert Chimison, Annie Brown, and Austin Mitchell.

[356] It was edited by Dave Shaw, contains original music by Dan Powell, and was engineered by Chris Wood.

[357] That's it for the daily.

[358] I'm Michael Babarro.

[359] See you tomorrow.