Ep. 318 - Newco Takes on CV Risk. Plus: Disrupting Vaccines

WEBVTT

00:00:00.000 --> 00:00:01.735
[AI-generated transcript.]

00:00:01.735 --> 00:00:31.530
<v Jeff Cranmer>Two of biotech's biggest names are bringing the disease interception model to cardiovascular risk with a startup that's made its debut today, we'll discuss  Corsera from John Maraganore and Clive Meanwell on the latest BioCentury this week Podcast plus FDA has been quietly positioning itself to disrupt the childhood vaccine schedule.

00:00:31.830 --> 00:00:45.177
<v Jeff Cranmer>We'll hear the latest from our Washington editor, Steve Usdin, on what is happening at FDA as well as changes to the Medicare Drug Negotiation program.

00:00:45.545 --> 00:00:55.320
<v Jeff Cranmer>And we have Simone back and she has been dedicated to her US open viewing and she'll give us an update on the big.

00:00:55.688 --> 00:00:58.924
<v Jeff Cranmer>Coco Naomi Showdown.

00:00:59.259 --> 00:01:02.962
<v Jeff Cranmer>That happened over in, where do they hold that thing?

00:01:02.962 --> 00:01:04.096
<v Jeff Cranmer>Queens, Brooklyn.

00:01:04.263 --> 00:01:04.831
<v Jeff Cranmer>Who knows?

00:01:05.031 --> 00:01:06.533
<v Jeff Cranmer>I got a bone up on my tennis.

00:01:06.965 --> 00:01:14.040
<v Jeff Cranmer>I'm Jeff Cranmer, executive editor here at BioCentury and host of the BioCentury this week podcast.

00:01:14.174 --> 00:01:15.608
<v Jeff Cranmer>And joining me today are

00:01:16.341 --> 00:01:18.111
<v Simone Fishburn>Simone Fishburn, Editor in Chief.

00:01:18.644 --> 00:01:20.346
<v Steve Usdin>Steve Usdin, Washington Editor.

00:01:20.746 --> 00:01:23.415
<v Paul Bonanos>And Paul Bonanos, Director of Biopharma Intelligence.

00:01:24.016 --> 00:01:24.349
<v Jeff Cranmer>All right.

00:01:24.349 --> 00:01:26.152
<v Jeff Cranmer>Thanks for joining me peeps.

00:01:26.218 --> 00:01:36.061
<v Jeff Cranmer>Two veteran biotech leaders, are launching a new company with ambitions in the CV disease space, you talk to them.

00:01:36.061 --> 00:01:37.530
<v Jeff Cranmer>Paul, tell us what you learned.

00:01:38.164 --> 00:01:38.730
<v Paul Bonanos>Sure.

00:01:38.998 --> 00:01:45.838
<v Paul Bonanos>so yeah, the story broke this morning and I had a chance to catch up last week with John Maraganore and Clive Meanwell, you mentioned them both.

00:01:46.706 --> 00:01:48.441
<v Paul Bonanos>obviously both have been around a long time.

00:01:48.441 --> 00:01:56.715
<v Paul Bonanos>I think most people know, uh, John was co-founder and CEO of Alnylam led the company for a very long time before handing off his roles a few years ago.

00:01:57.082 --> 00:02:03.522
<v Paul Bonanos>And Clive was CEO of the Medicines Co. which Novartis acquired for about $10 billion a few years back.

00:02:04.189 --> 00:02:06.692
<v Paul Bonanos>So, um, these two people have worked together before.

00:02:07.359 --> 00:02:12.899
<v Paul Bonanos>the Medicines Co. buyout centered on a drug we now know as Leqvio also known as inclisiran.

00:02:12.931 --> 00:02:16.002
<v Paul Bonanos>That targets PCSK9 to treat high cholesterol.

00:02:16.436 --> 00:02:21.074
<v Paul Bonanos>It originated with Alnylam, Medicines Co. licensed it, and now it's Novartis to sell.

00:02:21.540 --> 00:02:23.209
<v Paul Bonanos>there's also a connection further back.

00:02:23.242 --> 00:02:34.653
<v Paul Bonanos>Uh, going back to 1997, Maraganore was an inventor of, uh, a thrombin inhibitor Angiomax, AKA bivalirudin, which Medicines Co. brought to market via partnership.

00:02:35.187 --> 00:02:40.592
<v Paul Bonanos>So what they're up to now, they've launched a cardiovascular health startup called  Corsera  Health.

00:02:40.627 --> 00:02:42.294
<v Paul Bonanos>And it has two things going on.

00:02:42.294 --> 00:02:53.438
<v Paul Bonanos>One is a dual acting RNAI therapy that, also targets PCSK9, like inclisiran, also targets angiotensinogen to treat high blood pressure.

00:02:53.973 --> 00:03:00.212
<v Paul Bonanos>you may recognize the second target from another Alnylam program, zilebesiran, that's in late stage clinical testing.

00:03:00.712 --> 00:03:03.883
<v Paul Bonanos>Corsera 's, program is headed into the clinic this year.

00:03:04.217 --> 00:03:16.062
<v Paul Bonanos>The other thing they have is a risk evaluation tool that's intended to identify people who are more likely to develop CV disease and find them earlier in life, rather than sort of wait for them to get diagnosed.

00:03:16.062 --> 00:03:17.563
<v Paul Bonanos>It's a software tool.

00:03:17.663 --> 00:03:19.264
<v Paul Bonanos>It uses AI in some component.

00:03:19.264 --> 00:03:28.473
<v Paul Bonanos>We didn't get too far into the details of how the software works, but, John described it as an algorithmic tool that assesses risk of developing CV disease.

00:03:28.974 --> 00:03:43.423
<v Paul Bonanos>it's not a diagnostic, and just to be clear, it's not a companion diagnostic that goes with the therapy, but it's a way to figure out early on how much risk a person has of developing CV disease and then the person and their doctor can come up with a treatment strategy, which.

00:03:43.789 --> 00:03:46.693
<v Paul Bonanos>You know, may, may or may not include  Corsera 's therapy.

00:03:46.925 --> 00:03:50.062
<v Paul Bonanos>and this is, you mentioned in the category of disease interception.

00:03:50.062 --> 00:03:51.965
<v Paul Bonanos>We've written about that before, some too.

00:03:52.899 --> 00:04:03.810
<v Simone Fishburn>Let me ask you about that and maybe ask Steve as well, because I think it's, likely that we are just gonna see more and more of tools like these AI tools maybe launched along with a company.

00:04:04.644 --> 00:04:08.715
<v Simone Fishburn>Now you pointed out that this is not a companion diagnostic.

00:04:09.115 --> 00:04:12.451
<v Simone Fishburn>So Steve, do regulators care about this?

00:04:12.451 --> 00:04:15.722
<v Simone Fishburn>Is this something that just exists only in the commercial space?

00:04:16.055 --> 00:04:16.855
<v Simone Fishburn>how do you look at that?

00:04:17.456 --> 00:04:18.858
<v Steve Usdin>regulators do care about it.

00:04:19.259 --> 00:04:27.899
<v Steve Usdin>Regulators around the world have not just FDA are trying to get their hands, their arms around, those kinds of tools and to think about how to regulate them.

00:04:28.166 --> 00:04:29.968
<v Steve Usdin>you know, the, the potential is enormous.

00:04:30.336 --> 00:04:34.706
<v Steve Usdin>and the, um, the challenges are also substantial because if you think about it.

00:04:35.341 --> 00:04:38.644
<v Steve Usdin>Unlike just about any other product, it's protean, right?

00:04:38.644 --> 00:04:43.483
<v Steve Usdin>It's gonna keep changing the AI changes as it learns more.

00:04:43.783 --> 00:04:49.088
<v Steve Usdin>So how do you, how do you regulate something that isn't gonna be the same two days in a row?

00:04:49.521 --> 00:04:50.456
<v Steve Usdin>that's a challenge.

00:04:50.757 --> 00:05:05.071
<v Steve Usdin>I think a lot of the regulation around it is going to depend o n the kinds of decisions that are made based on it, I think regulators around the world, they're, they're settling on a, a risk-based, uh, different kinds of risk-based frameworks for these AI tools.

00:05:05.504 --> 00:05:14.079
<v Steve Usdin>where the, the amount of regulation and the amount of scrutiny, is going to be highly dependent on the consequences of the decisions that are made based on them.

00:05:14.346 --> 00:05:27.726
<v Steve Usdin>and there's also gonna have to be an ongoing, monitoring of safety issues, both by the companies that, manufacture that, that make the AI tools and by, providers that use them.

00:05:27.994 --> 00:05:36.903
<v Steve Usdin>it's, we're gonna see a lot more of this and we're gonna see a lot more kind of experimentation around the world about regulatory frameworks for those kinds of tools.

00:05:37.470 --> 00:05:44.776
<v Simone Fishburn>Paul, you know, I have a question for you as well, because you know John Maraganore, we've spoken to him obviously over the years, and he's been one of the.

00:05:45.177 --> 00:05:50.817
<v Simone Fishburn>Forward thinkers really in terms of pricing models  innovative pricing models, sorry.

00:05:51.184 --> 00:05:55.187
<v Simone Fishburn>Wondering whether he talked to you about the payer aspect?

00:05:55.187 --> 00:06:04.096
<v Simone Fishburn>I'm assuming that he believes that payers will want this kind of information and is that part of the company's thesis?

00:06:04.297 --> 00:06:12.038
<v Paul Bonanos>Well, it, it's,  I should mention, they, they stress that there is no business model yet around  the tool, the AI tool.

00:06:12.338 --> 00:06:17.276
<v Paul Bonanos>and on the, on the therapeutic side, the path is much more, um, well-defined.

00:06:17.744 --> 00:06:20.980
<v Paul Bonanos>it's not clear yet how it will shake out for reimbursement.

00:06:20.980 --> 00:06:21.581
<v Paul Bonanos>I would say.

00:06:21.646 --> 00:06:32.959
<v Paul Bonanos>Um, it is not unprecedented as well, though we should mention, Provention Bio and Tzield teplizumab, which is the, approved therapy to delay onset of type 1 diabetes.

00:06:33.358 --> 00:06:38.730
<v Paul Bonanos>And I think it's been pretty clear that that that there is a market for something like that.

00:06:38.730 --> 00:06:41.000
<v Paul Bonanos>It may just be a very slow growing one.

00:06:41.767 --> 00:06:54.146
<v Paul Bonanos>that's a, a therapy that Sanofi paid $2.9 billion, to acquire and sales of the product are now, in the first half of this year, were 29 million Euro, about 33, 34 million U.S.

00:06:54.713 --> 00:06:59.185
<v Paul Bonanos>so there is a path to market for a disease interception for people who aren't sick yet.

00:06:59.619 --> 00:07:04.824
<v Paul Bonanos>But, I don't think it's clear, how reimbursement will work for something like  Corsera 's therapy.

00:07:05.223 --> 00:07:08.494
<v Paul Bonanos>I'm drawing the comparison, but it's two very different situations, right?

00:07:08.494 --> 00:07:14.065
<v Paul Bonanos>I mean, type 1 diabetes, delaying onset of type 1 diabetes is a much smaller indication than CV disease.

00:07:14.065 --> 00:07:16.201
<v Paul Bonanos>Pretty much the biggest killer in the world, right?

00:07:16.769 --> 00:07:18.603
<v Paul Bonanos>so how, how far will people go?

00:07:18.603 --> 00:07:25.244
<v Paul Bonanos>How far will regulators or payers go,  to establish this commercial path and for whom?

00:07:25.745 --> 00:07:31.483
<v Paul Bonanos>and it's up to the company to, sort of make the market and create the market for something like this.

00:07:31.483 --> 00:07:33.985
<v Paul Bonanos>It's, it's very different from treating disease that already exists.

00:07:35.221 --> 00:07:39.291
<v Simone Fishburn>So just one last word, Paul, about the therapy itself.

00:07:39.524 --> 00:07:44.629
<v Simone Fishburn>Is this effectively going to now be a competitor to inclisira to Leqvio?

00:07:45.163 --> 00:07:45.730
<v Paul Bonanos>could be.

00:07:45.730 --> 00:07:46.331
<v Paul Bonanos>Yes.

00:07:46.331 --> 00:07:51.903
<v Paul Bonanos>Um, and the idea is to simplify, by, instead of having two administrations to have one.

00:07:52.672 --> 00:07:53.605
<v Paul Bonanos>It could be competitive.

00:07:53.605 --> 00:07:59.745
<v Paul Bonanos>Obviously the timelines are quite different, Leqvio being on the market and, um, this one just now entering the clinic.

00:08:00.146 --> 00:08:10.389
<v Paul Bonanos>and it's also not clear whether this will be chiefly prescribed to people to stave off disease or, to go to people who are already, entering cardiovascular disease later in life.

00:08:11.189 --> 00:08:13.326
<v Jeff Cranmer>All right, thanks for that, Paul.

00:08:13.326 --> 00:08:14.293
<v Jeff Cranmer>Uh, Paul's story.

00:08:15.026 --> 00:08:22.968
<v Jeff Cranmer>The latest in our emerging company profile series is up on BioCentury dot com.

00:08:22.968 --> 00:08:33.712
<v Jeff Cranmer>You can also find it at the link in the show notes and we are gonna take a quick break and then we'll be back to talk about what is going on in Washington.

00:08:34.145 --> 00:08:38.083
<v Alanna Farro>BioCentury This Week is brought to you by BioCentury Grand Rounds Europe.

00:08:39.818 --> 00:08:45.124
<v Alanna Farro>Grand Rounds, BioCentury's R&D conference, will make its European debut in 2025.

00:08:45.825 --> 00:08:51.163
<v Alanna Farro>Join us to debate key translational bottlenecks and unlock scientific breakthroughs with commercial potential.

00:08:51.663 --> 00:09:05.076
<v Alanna Farro>Connect with VCs, academic innovators, and biopharma R&D and BD leaders to explore cutting edge advancements in early stage R&D as we dive into disease biology, therapeutic modalities, and enabling technologies.

00:09:05.677 --> 00:09:09.248
<v Alanna Farro>Join us for the inaugural BioCentury Grand Grounds Europe in Cambridge.

00:09:09.248 --> 00:09:11.417
<v Alanna Farro>U.K. the September 17th to 19th.

00:09:11.716 --> 00:09:15.421
<v Alanna Farro>Register and learn more at BioCenturyGrandRoundsEurope.com.

00:09:17.623 --> 00:09:27.933
<v Jeff Cranmer>Well, it is back to school time at last on the U.S. East Coast and for us at BioCentury for the past 33 years.

00:09:27.933 --> 00:09:34.774
<v Jeff Cranmer>That means publishing our signature issue of the year, and that is called Back to School.

00:09:35.307 --> 00:09:40.379
<v Jeff Cranmer>It's a forward looking package that looks at a broad issue, critical to the biopharma industry.

00:09:40.379 --> 00:09:42.648
<v Jeff Cranmer>And this year, Steve, one man show.

00:09:42.682 --> 00:09:45.985
<v Jeff Cranmer>Well, of course you had some, uh, crack editors.

00:09:46.251 --> 00:09:47.552
<v Jeff Cranmer>Steve, give us a quick teaser.

00:09:48.421 --> 00:10:00.131
<v Steve Usdin>Basically what I did this year is I said, look, imagine that you're starting with a blank sheet of paper and you're creating an optimal medical products regulator for the United States.

00:10:00.332 --> 00:10:01.634
<v Steve Usdin>How would you go about doing it?

00:10:01.900 --> 00:10:09.542
<v Steve Usdin>and I and I talked to a lot of people at FDA, former FDA people, CEOs of biopharma companies, academics.

00:10:09.908 --> 00:10:16.548
<v Steve Usdin>And came up with, a prescription and, and I'll be the first person to say that it, it isn't definitive, it isn't the last word.

00:10:16.548 --> 00:10:23.522
<v Steve Usdin>It's really intended to spark a discussion, a debate about,  how FDA, should be, reorganized.

00:10:23.889 --> 00:10:28.059
<v Steve Usdin>couple of the points that I make, I suggest that, FDA's medical product.

00:10:29.361 --> 00:10:32.530
<v Steve Usdin>Function should be separated, from its other functions.

00:10:32.597 --> 00:10:54.854
<v Steve Usdin>In other words, what's now the Center for Biologics, the Center for Drugs, and the Center for Devices should be separated from tobacco, cosmetics, veterinary products, And I also suggest that the medical products regulation should be oriented and should be organized around, clinical, outcomes around clinical functions.

00:10:55.053 --> 00:11:02.995
<v Steve Usdin>and suggest that the Oncology Center of Excellence should be a model for how,  medical products regulation in the United States should be organized.

00:11:04.029 --> 00:11:05.464
<v Steve Usdin>As you said, it's a big package.

00:11:05.464 --> 00:11:07.533
<v Steve Usdin>There's seven stories, there's a lot more to it.

00:11:07.932 --> 00:11:12.638
<v Steve Usdin>I hope that, um, listeners, take the time to read the package, respond to it, think about it.

00:11:13.105 --> 00:11:19.678
<v Steve Usdin>You'll also have the opportunity to, um, listen and watch, Simone and I talk about it on The BioCentury Show later this week.

00:11:20.413 --> 00:11:27.186
<v Jeff Cranmer>And that is our sister podcast, available in audio and video form on BioCentury's YouTube channel.

00:11:27.552 --> 00:11:30.523
<v Jeff Cranmer>And we did do a. Back to school a little differently this year.

00:11:30.755 --> 00:11:35.193
<v Jeff Cranmer>traditionally, as I said, we really released it around the U.S. Labor Day holiday.

00:11:35.528 --> 00:11:45.004
<v Jeff Cranmer>this year we released it in mid August, and we will hear from Simone in a letter from the editor this week.

00:11:45.303 --> 00:11:48.073
<v Jeff Cranmer>and that will contain links to all seven stories.

00:11:48.073 --> 00:11:50.743
<v Jeff Cranmer>And of course, you'll have the podcast.

00:11:50.975 --> 00:11:52.010
<v Jeff Cranmer>As well.

00:11:52.311 --> 00:12:03.621
<v Jeff Cranmer>Now, this time of year is also a, uh, time of year, very special, to Simone, the U.S. Open,  happening in Flushing Meadows, New York.

00:12:03.621 --> 00:12:15.100
<v Jeff Cranmer>I always get a vision of Homer Simpsons trip to Manhattan and, the greater New York area where he, uh, wanders through Flushing Meadows and it's, uh.

00:12:15.433 --> 00:12:16.902
<v Jeff Cranmer>It's a really iconic scene.

00:12:16.902 --> 00:12:22.140
<v Jeff Cranmer>But, Simone, uh, Skinner, the Joker, Alcaraz, who do you think is gonna take it this year?

00:12:22.807 --> 00:12:24.076
<v Simone Fishburn>Sinner, I

00:12:24.309 --> 00:12:25.144
<v Jeff Cranmer>Si Sinner.

00:12:25.410 --> 00:12:25.945
<v Simone Fishburn>Yeah, yeah.

00:12:25.945 --> 00:12:26.144
<v Simone Fishburn>Yeah.

00:12:26.345 --> 00:12:27.346
<v Simone Fishburn>So, um, you

00:12:27.546 --> 00:12:30.816
<v Jeff Cranmer>that's that's 'cause Principal Skinner on Simpsons it.

00:12:30.816 --> 00:12:31.182
<v Jeff Cranmer>Sorry.

00:12:31.182 --> 00:12:32.250
<v Jeff Cranmer>It was a little slipped there.

00:12:32.283 --> 00:12:32.485
<v Jeff Cranmer>So.

00:12:32.684 --> 00:12:41.226
<v Simone Fishburn>so, you know, I always try to find like a, a theme that's relevant to biotech and I think this year I wanna go with resilience.

00:12:41.293 --> 00:12:41.894
<v Simone Fishburn>Okay.

00:12:42.227 --> 00:12:43.028
<v Simone Fishburn>So.

00:12:43.328 --> 00:12:48.167
<v Simone Fishburn>one of the standout matches was Naomi Osaka against Coco Gauff.

00:12:48.667 --> 00:12:55.875
<v Simone Fishburn>Naomi Osaka you've got a root for her if only because she has, as several others have.

00:12:55.875 --> 00:13:00.678
<v Simone Fishburn>She's had a child and come back since then, which is very difficult to do in tennis.

00:13:00.678 --> 00:13:02.148
<v Simone Fishburn>And Coco is a local favorite.

00:13:02.782 --> 00:13:11.690
<v Simone Fishburn>But you know, go to the resilience thing because to really reach the top, you gotta go through a lot of failures.

00:13:11.724 --> 00:13:21.466
<v Simone Fishburn>There's this very famous commencement speech by Roger Federer from last year where he talks about, even though he won like 80% of his matches, he won only 54% of his points or something.

00:13:21.466 --> 00:13:30.743
<v Simone Fishburn>So there's a lot of loss and failure that goes on, and I guess that's what CEOs need to do and biotech right now, they just need to keep picking themselves up.

00:13:31.043 --> 00:13:32.711
<v Simone Fishburn>and going at it again.

00:13:32.711 --> 00:13:39.585
<v Simone Fishburn>I know that, Steve feels like that a little bit as he watches the FDA undergo massive changes.

00:13:39.784 --> 00:13:42.721
<v Simone Fishburn>that agency's gonna require a little bit of resilience.

00:13:42.721 --> 00:13:55.466
<v Simone Fishburn>So I don't know if you guys wanna pick that up and add the thread there, but you don't get anywhere in our industry without being able to take a few losses and then, uh, still pick yourself up and keep going at it.

00:13:56.701 --> 00:13:58.303
<v Jeff Cranmer>Well, I, we will head there in a second.

00:13:58.303 --> 00:13:59.205
<v Jeff Cranmer>I, I, I need to hear.

00:13:59.504 --> 00:14:01.039
<v Jeff Cranmer>Your men's winner's gonna be?

00:14:01.072 --> 00:14:01.139
<v Simone Fishburn>Alcaraz.

00:14:02.707 --> 00:14:03.442
<v Jeff Cranmer>I love that man.

00:14:03.875 --> 00:14:05.376
<v Jeff Cranmer>He's gotta watch the hair grow back.

00:14:05.543 --> 00:14:07.011
<v Jeff Cranmer>he did the buzz cut thing.

00:14:07.379 --> 00:14:08.214
<v Jeff Cranmer>That's maybe it.

00:14:08.214 --> 00:14:10.014
<v Jeff Cranmer>Maybe Steve, you need the buzz cut.

00:14:11.082 --> 00:14:20.392
<v Jeff Cranmer>Well, a lot of, a lot of the teenagers today, uh, I can say as, uh, the, uh, father of 15-year-old boy mullets have come back and, uh, I really question.

00:14:20.658 --> 00:14:22.961
<v Simone Fishburn>do you think at BioCentury we should just give people a choice?

00:14:22.961 --> 00:14:24.529
<v Simone Fishburn>Mullet or buzzcut That's it.

00:14:24.697 --> 00:14:26.264
<v Steve Usdin>Well, the, idea of the, yeah.

00:14:26.264 --> 00:14:26.432
<v Steve Usdin>yeah.

00:14:26.432 --> 00:14:29.301
<v Steve Usdin>Well, the idea of the mullet is business in the front and party in the back.

00:14:29.301 --> 00:14:34.606
<v Steve Usdin>So when you're on Zoom, people won't even know if you've got a, got a mullet if you do it properly.

00:14:36.442 --> 00:14:36.808
<v Jeff Cranmer>man.

00:14:36.808 --> 00:14:43.716
<v Jeff Cranmer>When, when I was a kid it was like mohawks and you know, you could do the Robert Smith of the Cure hair and all that stuff,

00:14:43.749 --> 00:14:44.984
<v Simone Fishburn>don't, don't even go there.

00:14:44.984 --> 00:14:48.287
<v Simone Fishburn>I'm, I'm like of the big hair, eighties and early nineties kind

00:14:48.419 --> 00:14:48.953
<v Jeff Cranmer>All right.

00:14:48.953 --> 00:14:49.822
<v Jeff Cranmer>I I like it.

00:14:49.822 --> 00:14:50.422
<v Jeff Cranmer>I like it.

00:14:50.755 --> 00:14:56.695
<v Jeff Cranmer>Well, Steve, uh, a lot of talk last week about the turmoil at CDC.

00:14:56.861 --> 00:15:09.707
<v Jeff Cranmer>it was in the media spotlight, but,  you know, as you, you were mentioning to me, uh, sort of a quieter but potentially more consequential drama was also unfolding last week at FDA.

00:15:09.741 --> 00:15:10.576
<v Jeff Cranmer>Do you wanna tell us about that?

00:15:11.176 --> 00:15:19.918
<v Steve Usdin>Yeah, so, so like you say, you know, the turmoil at at CDC firing the director, three top scientists, resigning, it got a lot of attention quite rightly.

00:15:20.251 --> 00:15:27.725
<v Steve Usdin>so did, FDA's narrowing of the approvals of COVID vaccines, but there's something that was really important that flew under the radar.

00:15:28.793 --> 00:15:42.441
<v Steve Usdin>In his decision memo about the Pfizer BTech COVID vaccine, CBER Director, Vinay Prasad precluded co-administration of the COVID vaccine with flu or RSV vaccines.

00:15:43.107 --> 00:15:45.210
<v Steve Usdin>This was a big deal for two reasons.

00:15:45.210 --> 00:15:49.581
<v Steve Usdin>One affecting Pfizer and COVID and the other, I think potentially having even bigger impacts.

00:15:50.249 --> 00:15:51.984
<v Steve Usdin>So before Prasad's decision.

00:15:51.984 --> 00:16:00.024
<v Steve Usdin>CBER staff had given Pfizer the green light to include co-administration of flu and RSV on its label.

00:16:00.426 --> 00:16:17.342
<v Steve Usdin>And the reason we know that, besides the fact that people at FDA told me that is that Pfizer has already printed labels and inserted them in hundreds of thousands of cartons of vaccines saying that, that the vaccine can be co-administered with flu and RSV vaccines.

00:16:17.676 --> 00:16:24.216
<v Steve Usdin>So Prasad's decision could have forced Pfizer to rip open every carton and replace the labels.

00:16:24.582 --> 00:16:31.889
<v Steve Usdin>This would've disrupted distribution just as shipments were starting for the fall season when respiratory infection surge.

00:16:32.323 --> 00:16:40.264
<v Steve Usdin>Pfizer got FDA to agree instead to the company, sending letters to healthcare providers, telling them not to coadminister the vaccines.

00:16:40.666 --> 00:16:44.168
<v Steve Usdin>And that letter's posted on FDA's website.

00:16:44.168 --> 00:16:49.541
<v Steve Usdin>Prasad didn't cite any evidence that Coadminister is not safe or effective.

00:16:49.908 --> 00:17:00.952
<v Steve Usdin>Rather, he said that he isn't persuaded by the evidence supporting it, and he said that that evidence is based on non-inferiority studies with confidence intervals that he thinks are too permissive.

00:17:01.552 --> 00:17:06.557
<v Steve Usdin>the interesting thing is, is that CDC and a number of academic groups have looked into the same issue.

00:17:06.991 --> 00:17:23.776
<v Steve Usdin>They've conducted studies, and the studies that they've conducted according to CDC, American College of Physicians, infectious Disease Society of America, show that it's safe and effective to coadminister the COVID vaccines with the flu and RSV vaccines.

00:17:24.410 --> 00:17:28.012
<v Steve Usdin>So kind of Pfizer dodged a bullet there.

00:17:28.346 --> 00:17:36.422
<v Steve Usdin>It remains be seen what the impact of is gonna be  on the seasons uptake of flu and, RSV vaccines.

00:17:36.622 --> 00:17:41.559
<v Steve Usdin>It's a whole lot more convenient for people to get them all at one time than it is in three different times.

00:17:41.993 --> 00:17:50.134
<v Steve Usdin>I think that uptake of the COVID vaccines gonna be extraordinarily low this year anyway, for a variety of reasons, including the narrowed indication that FDA is approved.

00:17:50.602 --> 00:17:53.838
<v Steve Usdin>Okay, so then you say, well, what's the bigger picture?

00:17:53.838 --> 00:17:54.105
<v Steve Usdin>Right.

00:17:54.673 --> 00:18:02.080
<v Steve Usdin>So the bigger picture is that Prasad made it clear that his concern about co-administration isn't limited to COVID vaccines.

00:18:02.413 --> 00:18:06.317
<v Steve Usdin>FDA Commissioner Marty Makary, HHS Secretary Robert F.

00:18:06.317 --> 00:18:17.096
<v Steve Usdin>Kennedy Jr. Have repeatedly said that they're skeptical of the childhood vaccine schedule, that they don't believe children need as many vaccines as they receive, and that the vaccination should be spaced out.

00:18:17.628 --> 00:18:33.077
<v Steve Usdin>So Prasad's policy of questioning the co-administration of vaccines could be invoked to support changing the vaccine schedule and even forcing companies to reformulate combination vaccines such as the measles, mumps, and rubella vaccine.

00:18:33.644 --> 00:18:37.883
<v Steve Usdin>This has been a goal of anti-vaccine advocates, including Kennedy for a long time.

00:18:38.217 --> 00:18:41.487
<v Steve Usdin>I think if it does happen, it would've catastrophic effects.

00:18:41.686 --> 00:18:48.393
<v Steve Usdin>Instead of going to the doctor three times over 12 to 15 months, parents would have to go a dozen or more times.

00:18:48.660 --> 00:18:53.731
<v Steve Usdin>I think it's likely that a lot of parents wouldn't do it, even if parents did do it.

00:18:53.932 --> 00:18:59.471
<v Steve Usdin>and even if the system could kind of withstand the added burden on, pediatricians to do this.

00:19:00.305 --> 00:19:08.881
<v Steve Usdin>Kids would be vulnerable to the, pathogens that they haven't been vaccinated against for, you know, a year or a year and a half.

00:19:09.248 --> 00:19:24.663
<v Steve Usdin>And there have been studies that have, shown that failing to coadminister, some of the vaccines, for example, with measles exposed children, to, um, to measles and, and actually resulted in outbreaks of measles because they hadn't gotten co-administration.

00:19:25.230 --> 00:19:25.596
<v Simone Fishburn>Okay.

00:19:25.631 --> 00:19:26.230
<v Simone Fishburn>Steve.

00:19:26.397 --> 00:19:28.066
<v Simone Fishburn>let me just dial back a minute.

00:19:28.166 --> 00:19:49.587
<v Simone Fishburn>So what I'm hearing you say is that Prasad doesn't like the evidence that the people under him or currently under him have used to authorize or approve these vaccines in their current f ormulations or co-administration with other vaccines.

00:19:49.587 --> 00:19:54.559
<v Simone Fishburn>So evidence was looked at by people at FDA and they approved it, right?

00:19:54.792 --> 00:19:58.430
<v Simone Fishburn>And now he's coming in and saying, well, I don't like that.

00:19:58.430 --> 00:20:00.097
<v Simone Fishburn>I'm not convinced by the evidence.

00:20:00.531 --> 00:20:07.105
<v Simone Fishburn>how is that different than when he was saying beforehand that he didn't really like Peter Marks overruling the people under him.

00:20:08.173 --> 00:20:12.611
<v Steve Usdin>Well, you know, I, I've said it a bunch of times since January.

00:20:13.211 --> 00:20:23.855
<v Steve Usdin>The hypocrisy ship in Washington sailed a long time ago, and I don't think you're gonna get very far by pointing out inconsistencies and, and hypocrisies in public policy.

00:20:24.088 --> 00:20:35.666
<v Steve Usdin>But I will say that you're right that, um CBER had concluded that it was safe to coadminister safe and effective to coadminister, COVID vaccines and flu and RSV vaccines.

00:20:35.968 --> 00:20:48.279
<v Steve Usdin>you may recall that when COVID vaccines were first received, emergency use authorization, FDA said that out of an abundance of caution that they shouldn't be co-administered with other vaccines.

00:20:48.614 --> 00:20:52.049
<v Steve Usdin>And then they came back later and said, that it's okay to do it.

00:20:52.049 --> 00:20:56.188
<v Steve Usdin>And CDC and other groups actually encouraged this co-administration.

00:20:56.555 --> 00:21:03.461
<v Steve Usdin>So yeah, and Prasad doesn't really, provide any data except his own personal skepticism to support this.

00:21:03.461 --> 00:21:09.268
<v Simone Fishburn>Well, that's what I wanted to drill down on a little bit, because let's go from there to the other things you talked about.

00:21:09.701 --> 00:21:16.508
<v Simone Fishburn>I don't know if Prasad, before he joined FDA, had raised alarms on these kinds of issues.

00:21:17.342 --> 00:21:25.217
<v Simone Fishburn>But you know, there's one thing where, a new leader comes in and says, going forward, this is how we're gonna look at certain data.

00:21:25.450 --> 00:21:28.452
<v Simone Fishburn>This is what we're going to do, this is what we're going to require.

00:21:28.686 --> 00:21:34.660
<v Simone Fishburn>But how common is it for somebody to come in and say, I just wanna reevaluate the way we did everything.

00:21:34.660 --> 00:21:43.969
<v Simone Fishburn>I don't like the way the old FDA was t reating statistical analysis or whatever the basis is, and so I'm gonna undo previous decisions.

00:21:44.935 --> 00:21:46.038
<v Steve Usdin>That's extraordinarily.

00:21:46.171 --> 00:21:46.904
<v Steve Usdin>Uncommon.

00:21:47.271 --> 00:22:07.291
<v Steve Usdin>And when it's done, when FDA changes its policies in the past that's been done through a kind of scientific consensus that's been developed, its best when it's developed in public, when, um, they can get input from the entire scientific community as well as, patients and other kind of stakeholders for doing it.

00:22:07.425 --> 00:22:12.263
<v Steve Usdin>What isn't common what i s extraordinary is to have a center director.

00:22:12.497 --> 00:22:18.569
<v Steve Usdin>second guess the decisions that, FDA staff have made and say, no, we're changing the policy.

00:22:18.936 --> 00:22:32.683
<v Steve Usdin>And, and the FDA staff essentially learn about it from the decision memo that senate director issues, as you know, Peter Marks, did it, uh, there were a few instances of doing him, doing that in the past that was about specific.

00:22:32.851 --> 00:22:34.819
<v Steve Usdin>Product, approval decisions.

00:22:34.986 --> 00:22:43.894
<v Steve Usdin>it wasn't kind of philosophically, turning the, the policy ship around, on something that's gonna affect a whole class of products, like vaccines.

00:22:44.996 --> 00:22:46.565
<v Simone Fishburn>So one more thing and humor me.

00:22:46.565 --> 00:22:47.632
<v Simone Fishburn>You know, I've been away.

00:22:47.632 --> 00:22:54.472
<v Simone Fishburn>I've been at a nephew's wedding in the U.K. and having a very chill time, not getting all upset about these kinds of things.

00:22:54.472 --> 00:22:58.410
<v Simone Fishburn>And I come back and I see that the CDC has kind of imploded.

00:22:58.743 --> 00:23:08.153
<v Simone Fishburn>and at the end of the day what really happened there is a, a few people just sort of put their foot down and said, no meaning no, they'll walk out, is how I understand this.

00:23:08.386 --> 00:23:10.888
<v Simone Fishburn>The agency, I dunno what the future is of that agency.

00:23:11.455 --> 00:23:24.935
<v Simone Fishburn>So do you think there's gonna be a ripple effect, Steve, from CDC into FDA, maybe even into NIH to a degree are the goings on within each of these agencies, which all report obviously into HHS.

00:23:25.369 --> 00:23:27.939
<v Simone Fishburn>To what degree do you think they spell from one end to the other?

00:23:28.440 --> 00:23:52.897
<v Steve Usdin>I would say that it is part of a coordinated effort that's being led by Robert Kennedy Jr. to upend disrupt, the vaccine, policy, of the United States and the things that are happening at CDC, at FDA, and at NIH are all part a coordinated effort, and it's not conspiracy thinking.

00:23:52.998 --> 00:23:56.334
<v Simone Fishburn>Well, I, I think that been open about not a secret.

00:23:56.934 --> 00:24:04.108
<v Simone Fishburn>what I, I guess what I'm asking is, is there a point at which people just are like, I can't support this anymore, I'm outta here.

00:24:04.442 --> 00:24:10.347
<v Simone Fishburn>And publicly, I mean, we've obviously know that a whole bunch of people have gone privately and do you think there's a tipping point, is what I'm

00:24:10.414 --> 00:24:14.318
<v Steve Usdin>Yeah, we've, we've passed the tipping point  and I would disagree with you a little bit.

00:24:14.318 --> 00:24:16.755
<v Steve Usdin>I don't think the CDC imploded.

00:24:16.755 --> 00:24:18.022
<v Steve Usdin>I think it was exploded.

00:24:19.124 --> 00:24:20.959
<v Steve Usdin>So there's a little, a little bit of a difference there.

00:24:21.192 --> 00:24:22.594
<v Steve Usdin>We, we've seen it already.

00:24:22.827 --> 00:24:26.698
<v Steve Usdin>at FDA, of course, ousting, Peter Marks, was part of that.

00:24:26.932 --> 00:24:42.646
<v Steve Usdin>there have been other officials, the official who was in charge of, biostatistics and post market pharmacovigilance at CBER was pushed out of his position by Vinay Prasad and, and forced to take a detail at CDER at the Center for Drugs.

00:24:42.881 --> 00:24:47.018
<v Steve Usdin>And Vinay Prasad has made himself acting, head of that division at CBER.

00:24:47.318 --> 00:24:49.221
<v Steve Usdin>There's a lot of other machinations that are going on.

00:24:49.221 --> 00:24:52.691
<v Steve Usdin>There are other people who have been fired, who have quit and so on.

00:24:52.691 --> 00:24:59.730
<v Steve Usdin>So, at least when it comes to, um, to vaccines, we've certainly gone past that tipping point.

00:24:59.798 --> 00:25:02.534
<v Steve Usdin>And, we're heading, in a direction which.

00:25:02.666 --> 00:25:06.605
<v Steve Usdin>I believe and I think, most public health experts believe, is troublesome and dangerous.

00:25:07.638 --> 00:25:11.076
<v Simone Fishburn>I mean, I, I actually wanna make a, a. A point here for our listeners, which is.

00:25:11.742 --> 00:25:18.383
<v Simone Fishburn>Regardless of people's political opinion, we try very, very hard BioCentury to tell it straight.

00:25:18.616 --> 00:25:24.655
<v Simone Fishburn>We, look for the science-based alternative argument that could support something.

00:25:24.655 --> 00:25:32.297
<v Simone Fishburn>I know that there are some people who will say, great things are happening at FDA and certain interactions with biotechs and things.

00:25:33.030 --> 00:25:45.309
<v Simone Fishburn>But I think that just what we're seeing on the vaccine front alone in terms of scientific, orthodox, or scientific rigor, really, really hard, you know, this is not necessarily a party political thing, really, really hard.

00:25:45.477 --> 00:25:48.313
<v Simone Fishburn>At some point you've just gotta stand up and say, this is wrong.

00:25:48.346 --> 00:25:54.251
<v Simone Fishburn>It's just not possible for us to find a science-based approach that supports this.

00:25:55.586 --> 00:25:56.488
<v Simone Fishburn>Where are we going now, Jeff?

00:25:59.057 --> 00:26:02.594
<v Jeff Cranmer>let's, um, hey, let's, uh, let's talk about Medicare.

00:26:02.861 --> 00:26:05.163
<v Jeff Cranmer>Um, there we go.

00:26:05.497 --> 00:26:19.243
<v Jeff Cranmer>Steve, uh, you've been digging into the, uh, effects of changes to the Medicare drug negotiation program,  that were included in that tax and budget bill Congress passed in July.

00:26:19.243 --> 00:26:19.678
<v Jeff Cranmer>What have you found?

00:26:20.679 --> 00:26:20.878
<v Steve Usdin>So.

00:26:21.413 --> 00:26:31.489
<v Steve Usdin>that bill, which, you know, which people call the Big Beautiful Bill,  it included an expansion of the orphan drug exemption from the Medicare Drug Price Negotiation Program.

00:26:32.057 --> 00:26:47.872
<v Steve Usdin>you recall the original bill, the IRA, that created the price negotiation program, created an exemption for orphan drugs, but was only if a drug had a single orphan designation that it was exempt from the IRA.

00:26:48.272 --> 00:26:52.410
<v Steve Usdin>That had a lot of unanticipated consequences.

00:26:52.544 --> 00:27:04.489
<v Steve Usdin>it led, to companies saying that they were abandoning some, orphan indications because they didn't want to have a second or a third, orphan indication that would, then trigger, Medicare drug price negotiations.

00:27:04.655 --> 00:27:06.724
<v Steve Usdin>Some big pharmas said that they were.

00:27:07.392 --> 00:27:14.798
<v Steve Usdin>Deprioritizing, orphan cancer indications, in favor of, more common indications and so on.

00:27:14.798 --> 00:27:18.536
<v Steve Usdin>So there were a lot of unintended consequences as a result of that.

00:27:18.769 --> 00:27:30.515
<v Steve Usdin>Now, what in the, in the new legislation, what they've done is they've said, okay, if a drug only has orphan indications, regardless of the number, it's exempt, from Medicare drug price negotiation.

00:27:31.915 --> 00:27:45.864
<v Steve Usdin>if its first indication is an orphan indication, if it's subsequently later, you know if it later gets a non-orphan indication, the timing for when it's eligible for Medicare drug price negotiation.

00:27:45.864 --> 00:27:50.969
<v Steve Usdin>That clock starts ticking with the first non-orphan indication.

00:27:51.502 --> 00:28:01.980
<v Steve Usdin>So, limiting the exemption in the original law, kind of instantly and unintentionally destroyed one business model for rare disease, drug development.

00:28:02.146 --> 00:28:09.487
<v Steve Usdin>And this model manufactures pieced together multiple small indications that are each too small to justify investments in R&D.

00:28:10.055 --> 00:28:21.900
<v Steve Usdin>What they do is they pursue multiple small indications, put together a package of them, in the expectation that altogether, there'll be enough return on, on the drug to justify the R&D.

00:28:22.366 --> 00:28:25.569
<v Steve Usdin>This is good for, for those, small companies that do that.

00:28:25.569 --> 00:28:31.976
<v Steve Usdin>It's typically small companies and of course, it's very good for the patients who have those orphan diseases.

00:28:32.343 --> 00:28:39.884
<v Steve Usdin>So in broadening the orphan exemption, Congress has again made that business model viable again.

00:28:40.250 --> 00:28:53.530
<v Steve Usdin>The other thing that it's done though, and by all accounts, this was unanticipated by, most of the, uh, lawmakers who were working on this and also, by the companies that were, pushing for this, um, change in the law.

00:28:53.798 --> 00:28:58.103
<v Steve Usdin>It's gonna delay price negotiations for some blockbuster drugs.

00:28:58.502 --> 00:29:04.409
<v Steve Usdin>The most obvious examples are Keytruda from Merck and Opdivo from, Bristol Myers.

00:29:04.843 --> 00:29:13.451
<v Steve Usdin>Both of those drugs were first approved for an orphan indication, and then a year later they were approved for non-orphan indications.

00:29:13.817 --> 00:29:37.541
<v Steve Usdin>That means that the first date that they're gonna be eligible for Medicare drug price negotiation has been put back, by a year for each of those, I've got a story that's coming out this week describing other examples of drugs, that are gonna have delayed price negotiation and also that may never be subject, to price negotiation because they have multiple, orphan indications.

00:29:37.541 --> 00:29:46.651
<v Steve Usdin>And as long as their manufacturers don't, get approval for, non ORP indication, then they will be exempt from price negotiation, forever.

00:29:46.951 --> 00:29:58.429
<v Steve Usdin>The other thing that I'd say that, that that's interesting that's happened as a result of this change is you're very likely, we're very likely to see, changes in the pipeline prioritization of pharmas.

00:29:58.762 --> 00:30:07.005
<v Steve Usdin>they're gonna shift back, to, the pre, IRA model where they're gonna go first, um, with orphan indications, especially for cancer drugs.

00:30:07.438 --> 00:30:28.660
<v Steve Usdin>there's gonna be a temptation to either only have orphan indications, in which case your drugs would never be subject to the, uh, Medicare drug price negotiation or to, push off the non-orphan indication, until later in the drug's, lifecycle so that you could get, you can extend your, your runway before negotiations.

00:30:28.992 --> 00:30:29.993
<v Steve Usdin>one final thing here.

00:30:29.993 --> 00:30:30.862
<v Steve Usdin>That's interesting.

00:30:31.162 --> 00:30:33.964
<v Steve Usdin>It's another kind of unintended consequence of this.

00:30:34.231 --> 00:30:39.037
<v Steve Usdin>So I think that we're gonna see, to an extent this supports higher launch prices, right?

00:30:39.037 --> 00:30:50.248
<v Steve Usdin>Because if a drug launches first for an orphan indication, typically pricing is higher and the manufacturers justify that higher pricing because, there's gonna be a limited market.

00:30:50.248 --> 00:30:51.316
<v Steve Usdin>It's an orphan market, right?

00:30:51.749 --> 00:30:55.486
<v Steve Usdin>Then when they get a non-orphan indication, here's what doesn't happen.

00:30:55.519 --> 00:31:01.491
<v Steve Usdin>What doesn't happen typically is the manufacturer looking at it and saying, oh, now I've got a non-orphan indication.

00:31:01.726 --> 00:31:04.295
<v Steve Usdin>I've got a much bigger market, so I'm gonna lower the price.

00:31:04.429 --> 00:31:05.596
<v Steve Usdin>that just isn't a thing.

00:31:05.930 --> 00:31:08.232
<v Steve Usdin>so these are all kinds of things to, to think about.

00:31:08.766 --> 00:31:09.433
<v Jeff Cranmer>all right Steve.

00:31:09.433 --> 00:31:10.768
<v Jeff Cranmer>Thanks for that update.

00:31:11.035 --> 00:31:14.905
<v Jeff Cranmer>Out for Steve's story on BioCentury dot com.

00:31:15.272 --> 00:31:20.278
<v Jeff Cranmer>And if you're liking what you're hearing,  subscribe, follow us.

00:31:20.478 --> 00:31:21.712
<v Jeff Cranmer>leave us a review.

00:31:21.712 --> 00:31:23.114
<v Jeff Cranmer>We'd love to hear from you.

00:31:23.381 --> 00:31:25.215
<v Jeff Cranmer>And Simone, you didn't mention that.

00:31:25.215 --> 00:31:36.461
<v Jeff Cranmer>Uh, in addition to the buzz cut, Your man Alcaraz is going for a hot pink sleeveless top with purple shorts and purple shoes.

00:31:36.560 --> 00:31:41.833
<v Jeff Cranmer>And, uh, I gotta say,  Wimbledon, uh, organizers take note.

00:31:42.066 --> 00:31:44.269
<v Jeff Cranmer>A little more colorful, little more colorful.

00:31:44.535 --> 00:31:55.179
<v Jeff Cranmer>All right, well, we'll be back with our sister podcast later this week, Steve and Simone, digging deep into our back to school issue, we'll see you next week.

00:31:55.179 --> 00:31:56.146
<v Jeff Cranmer>Thanks for tuning in.

00:31:56.547 --> 00:32:03.387
<v Jeff Cranmer>And we appreciate Kendall Square Orchestra, which produces the music for all of BioCentury's podcasts.