September 2, 2025 • 32 mins
Two veteran biotech leaders are launching a new company with ambitions in the cardiovascular disease space. On the latest BioCentury This Week podcast, BioCentury’s analysts discuss the debut of Corsera Health, a biotech led by John Maraganore and Clive Meanwell that is developing an AI-guided early risk assessment tool alongside dual-acting therapy that could stave off heart disease.
The team then discusses how FDA has been quietly positioning itself to disrupt the childhood vaccine schedule, as well as the effects of changes to the Medicare drug negotiation program that were included in the tax and budget bill Congress passed in July.
View full story: https://www.biocentury.com/article/656897
#Corsera #DiseaseInterception #CardiovascularHealth #HeartDisease #FDA #VaccinePolicy #Medicare #DrugPricing
00:00 - Introduction
01:26 - Maraganore, Meanwell Newco
09:17 - BioCentury's Back to School
14:51 - Vaccine Disruption at FDA
26:01 - Medicare Drug Negotiations
To submit a question to BioCentury’s editors, email the BioCentury This Week team at podcasts@biocentury.com.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
[AI-generated transcript.]
Jeff Cranmer (00:01):
Two of biotech's biggest names are bringing
the disease interception modelto cardiovascular risk with a
startup that's made its debuttoday, we'll discuss Corsera
from John Maraganore andClive Meanwell on the latest
BioCentury this week Podcastplus FDA has been quietly
(00:26):
positioning itself to disruptthe childhood vaccine schedule.
We'll hear the latest from ourWashington editor, Steve Usdin,
on what is happening at FDA aswell as changes to the Medicare
Drug Negotiation program.
And we have Simone back andshe has been dedicated to her
(00:51):
US open viewing and she'llgive us an update on the big.
Coco Naomi Showdown.
That happened over in, wheredo they hold that thing?
Queens, Brooklyn.
Who knows?
I got a bone up on my tennis.
I'm Jeff Cranmer, executiveeditor here at BioCentury
(01:11):
and host of the BioCenturythis week podcast.
And joining me today are
Simone Fishburn (01:16):
Simone Fishburn, Editor in Chief.
Steve Usdin (01:18):
Steve Usdin, Washington Editor.
Paul Bonanos (01:20):
And Paul Bonanos, Director of
Biopharma Intelligence.
Jeff Cranmer (01:24):
All right.
Thanks for joining me peeps.
Two veteran biotech leaders,are launching a new company
with ambitions in the CVdisease space, you talk to them.
Paul, tell us what you learned.
Paul Bonanos (01:38):
Sure.
so yeah, the story broke thismorning and I had a chance to
catch up last week with JohnMaraganore and Clive Meanwell,
you mentioned them both.
obviously both havebeen around a long time.
I think most people know, uh,John was co-founder and CEO of
Alnylam led the company for avery long time before handing
off his roles a few years ago.
And Clive was CEO of theMedicines Co. which Novartis
(02:00):
acquired for about $10billion a few years back.
So, um, these two peoplehave worked together before.
the Medicines Co. buyoutcentered on a drug we
now know as Leqvio alsoknown as inclisiran.
That targets PCSK9 totreat high cholesterol.
It originated with Alnylam,Medicines Co. licensed it,
and now it's Novartis to sell.
(02:21):
there's also aconnection further back.
Uh, going back to 1997,Maraganore was an inventor
of, uh, a thrombin inhibitorAngiomax, AKA bivalirudin,
which Medicines Co. broughtto market via partnership.
So what they're up tonow, they've launched a
cardiovascular health startupcalled Corsera Health.
And it has two things going on.
(02:42):
One is a dual acting RNAItherapy that, also targets
PCSK9, like inclisiran, alsotargets angiotensinogen to
treat high blood pressure.
you may recognize the secondtarget from another Alnylam
program, zilebesiran, that'sin late stage clinical testing.
Corsera 's, program is headedinto the clinic this year.
(03:04):
The other thing they have isa risk evaluation tool that's
intended to identify people whoare more likely to develop CV
disease and find them earlierin life, rather than sort of
wait for them to get diagnosed.
It's a software tool.
It uses AI in some component.
We didn't get too far intothe details of how the
software works, but, Johndescribed it as an algorithmic
(03:24):
tool that assesses riskof developing CV disease.
it's not a diagnostic, andjust to be clear, it's not a
companion diagnostic that goeswith the therapy, but it's
a way to figure out early onhow much risk a person has
of developing CV disease andthen the person and their
doctor can come up with atreatment strategy, which.
You know, may, may or may notinclude Corsera 's therapy.
(03:46):
and this is, you mentionedin the category of
disease interception.
We've written aboutthat before, some too.
Simone Fishburn (03:52):
Let me ask you about that and maybe ask
Steve as well, because I thinkit's, likely that we are just
gonna see more and more oftools like these AI tools maybe
launched along with a company.
Now you pointed out that thisis not a companion diagnostic.
So Steve, do regulatorscare about this?
Is this something thatjust exists only in
(04:14):
the commercial space?
how do you look at that?
Steve Usdin (04:17):
regulators do care about it.
Regulators around theworld have not just FDA are
trying to get their hands,their arms around, those
kinds of tools and to thinkabout how to regulate them.
you know, the, thepotential is enormous.
and the, um, the challengesare also substantial because
if you think about it.
Unlike just about any otherproduct, it's protean, right?
(04:38):
It's gonna keep changing theAI changes as it learns more.
So how do you, how doyou regulate something
that isn't gonna be thesame two days in a row?
that's a challenge.
I think a lot of the regulationaround it is going to depend
o n the kinds of decisionsthat are made based on it,
I think regulators aroundthe world, they're, they're
(04:59):
settling on a, a risk-based, uh,different kinds of risk-based
frameworks for these AI tools.
where the, the amount ofregulation and the amount
of scrutiny, is going tobe highly dependent on the
consequences of the decisionsthat are made based on them.
and there's also gonna haveto be an ongoing, monitoring
of safety issues, both by thecompanies that, manufacture
(05:22):
that, that make the AI toolsand by, providers that use them.
it's, we're gonna see alot more of this and we're
gonna see a lot more kind ofexperimentation around the world
about regulatory frameworksfor those kinds of tools.
Simone Fishburn (05:37):
Paul, you know, I have a question for you
as well, because you know JohnMaraganore, we've spoken to
him obviously over the years,and he's been one of the.
Forward thinkers really in termsof pricing models innovative
pricing models, sorry.
Wondering whether he talkedto you about the payer aspect?
I'm assuming that he believesthat payers will want this
(05:59):
kind of information and is thatpart of the company's thesis?
Paul Bonanos (06:04):
Well, it, it's, I should mention,
they, they stress that thereis no business model yet
around the tool, the AI tool.
and on the, on the therapeuticside, the path is much
more, um, well-defined.
it's not clear yet how it willshake out for reimbursement.
I would say.
Um, it is not unprecedentedas well, though we should
(06:24):
mention, Provention Bio andTzield teplizumab, which is
the, approved therapy to delayonset of type 1 diabetes.
And I think it's been prettyclear that that that there is a
market for something like that.
It may just be a veryslow growing one.
that's a, a therapy that Sanofipaid $2.9 billion, to acquire
(06:46):
and sales of the product arenow, in the first half of this
year, were 29 million Euro,about 33, 34 million U.S.
so there is a path to marketfor a disease interception for
people who aren't sick yet.
But, I don't think it'sclear, how reimbursement
will work for somethinglike Corsera 's therapy.
I'm drawing the comparison,but it's two very different
(07:07):
situations, right?
I mean, type 1 diabetes,delaying onset of type 1
diabetes is a much smallerindication than CV disease.
Pretty much the biggestkiller in the world, right?
so how, how far will people go?
How far will regulators orpayers go, to establish this
commercial path and for whom?
and it's up to the companyto, sort of make the market
(07:29):
and create the marketfor something like this.
It's, it's very differentfrom treating disease
that already exists.
Simone Fishburn (07:35):
So just one last word, Paul,
about the therapy itself.
Is this effectively goingto now be a competitor
to inclisira to Leqvio?
Paul Bonanos (07:45):
could be.
Yes.
Um, and the idea is to simplify,by, instead of having two
administrations to have one.
It could be competitive.
Obviously the timelines arequite different, Leqvio being
on the market and, um, this onejust now entering the clinic.
and it's also not clear whetherthis will be chiefly prescribed
to people to stave off diseaseor, to go to people who are
(08:07):
already, entering cardiovasculardisease later in life.
Jeff Cranmer (08:11):
All right, thanks for that, Paul.
Uh, Paul's story.
The latest in our emergingcompany profile series is
up on BioCentury dot com.
You can also find it at the linkin the show notes and we are
gonna take a quick break andthen we'll be back to talk about
(08:31):
what is going on in Washington.
Alanna Farro (08:34):
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Jeff Cranmer (09:17):
Well, it is back to school time at
last on the U.S. East Coastand for us at BioCentury
for the past 33 years.
That means publishing oursignature issue of the year, and
that is called Back to School.
It's a forward lookingpackage that looks at a
(09:37):
broad issue, critical tothe biopharma industry.
And this year,Steve, one man show.
Well, of course you hadsome, uh, crack editors.
Steve, give us a quick teaser.
Steve Usdin (09:48):
Basically what I did this year is I said,
look, imagine that you'restarting with a blank sheet
of paper and you're creatingan optimal medical products
regulator for the United States.
How would you go about doing it?
and I and I talked to a lotof people at FDA, former FDA
people, CEOs of biopharmacompanies, academics.
(10:09):
And came up with, aprescription and, and I'll
be the first person to saythat it, it isn't definitive,
it isn't the last word.
It's really intended to spark adiscussion, a debate about, how
FDA, should be, reorganized.
couple of the points thatI make, I suggest that,
FDA's medical product.
Function should be separated,from its other functions.
(10:32):
In other words, what's now theCenter for Biologics, the Center
for Drugs, and the Center forDevices should be separated
from tobacco, cosmetics,veterinary products, And I
also suggest that the medicalproducts regulation should be
oriented and should be organizedaround, clinical, outcomes
(10:53):
around clinical functions.
and suggest that the OncologyCenter of Excellence should be a
model for how, medical productsregulation in the United
States should be organized.
As you said, it's a big package.
There's seven stories,there's a lot more to it.
I hope that, um, listeners, takethe time to read the package,
respond to it, think about it.
You'll also have the opportunityto, um, listen and watch, Simone
(11:16):
and I talk about it on TheBioCentury Show later this week.
Jeff Cranmer (11:20):
And that is our sister podcast, available
in audio and video form onBioCentury's YouTube channel.
And we did do a. Back to schoola little differently this year.
traditionally, as I said,we really released it around
the U.S. Labor Day holiday.
this year we released itin mid August, and we will
(11:41):
hear from Simone in a letterfrom the editor this week.
and that will containlinks to all seven stories.
And of course, you'llhave the podcast.
As well.
Now, this time of year isalso a, uh, time of year,
very special, to Simone,the U.S. Open, happening in
Flushing Meadows, New York.
(12:03):
I always get a vision of HomerSimpsons trip to Manhattan
and, the greater New York areawhere he, uh, wanders through
Flushing Meadows and it's, uh.
It's a really iconic scene.
But, Simone, uh, Skinner, theJoker, Alcaraz, who do you think
is gonna take it this year?
Simone Fishburn (12:22):
Sinner, I
Jeff Cranmer (12:24):
Si Sinner.
Simone Fishburn (12:25):
Yeah, yeah.
Yeah.
So, um, you
Jeff Cranmer (12:27):
that's that's 'cause Principal
Skinner on Simpsons it.
Sorry.
It was a little slipped there.
So.
Simone Fishburn (12:32):
so, you know, I always try to find like a,
a theme that's relevant tobiotech and I think this year
I wanna go with resilience.
Okay.
So.
one of the standout matches wasNaomi Osaka against Coco Gauff.
Naomi Osaka you've got a rootfor her if only because she
(12:53):
has, as several others have.
She's had a child and comeback since then, which is very
difficult to do in tennis.
And Coco is a local favorite.
But you know, go to theresilience thing because to
really reach the top, you gottago through a lot of failures.
There's this very famouscommencement speech by
(13:13):
Roger Federer from last yearwhere he talks about, even
though he won like 80% ofhis matches, he won only 54%
of his points or something.
So there's a lot of lossand failure that goes on,
and I guess that's whatCEOs need to do and biotech
right now, they just need tokeep picking themselves up.
and going at it again.
I know that, Steve feels likethat a little bit as he watches
(13:36):
the FDA undergo massive changes.
that agency's gonna requirea little bit of resilience.
So I don't know if you guyswanna pick that up and add
the thread there, but youdon't get anywhere in our
industry without being ableto take a few losses and
then, uh, still pick yourselfup and keep going at it.
Jeff Cranmer (13:56):
Well, I, we will head there in a second.
I, I, I need to hear.
Your men's winner's gonna be?
Simone Fishburn (14:01):
Alcaraz.
Jeff Cranmer (14:02):
I love that man.
He's gotta watchthe hair grow back.
he did the buzz cut thing.
That's maybe it.
Maybe Steve, youneed the buzz cut.
Well, a lot of, a lot ofthe teenagers today, uh,
I can say as, uh, the,uh, father of 15-year-old
boy mullets have come backand, uh, I really question.
Simone Fishburn (14:20):
do you think at BioCentury we should
just give people a choice?
Mullet or buzzcut That's it.
Steve Usdin (14:24):
Well, the, idea of the, yeah.
yeah.
Well, the idea of the mulletis business in the front
and party in the back.
So when you're on Zoom,people won't even know if
you've got a, got a mulletif you do it properly.
Jeff Cranmer (14:36):
man.
When, when I was a kid it waslike mohawks and you know, you
could do the Robert Smith of theCure hair and all that stuff,
Simone Fishburn (14:43):
don't, don't even go there.
I'm, I'm like of the big hair,eighties and early nineties kind
Jeff Cranmer (14:48):
All right.
I I like it.
I like it.
Well, Steve, uh, a lotof talk last week about
the turmoil at CDC.
it was in the media spotlight,but, you know, as you, you were
mentioning to me, uh, sort ofa quieter but potentially more
consequential drama was alsounfolding last week at FDA.
(15:09):
Do you wanna tell us about that?
Steve Usdin (15:11):
Yeah, so, so like you say, you know, the
turmoil at at CDC firing thedirector, three top scientists,
resigning, it got a lot ofattention quite rightly.
so did, FDA's narrowingof the approvals of COVID
vaccines, but there's somethingthat was really important
that flew under the radar.
In his decision memo about thePfizer BTech COVID vaccine,
(15:33):
CBER Director, Vinay Prasadprecluded co-administration
of the COVID vaccinewith flu or RSV vaccines.
This was a big dealfor two reasons.
One affecting Pfizer andCOVID and the other, I
think potentially havingeven bigger impacts.
So before Prasad's decision.
CBER staff had given Pfizerthe green light to include
(15:56):
co-administration of fluand RSV on its label.
And the reason we know that,besides the fact that people at
FDA told me that is that Pfizerhas already printed labels
and inserted them in hundredsof thousands of cartons of
vaccines saying that, that thevaccine can be co-administered
with flu and RSV vaccines.
(16:17):
So Prasad's decision could haveforced Pfizer to rip open every
carton and replace the labels.
This would've disrupteddistribution just as
shipments were startingfor the fall season when
respiratory infection surge.
Pfizer got FDA to agreeinstead to the company,
sending letters to healthcareproviders, telling them not
(16:38):
to coadminister the vaccines.
And that letter'sposted on FDA's website.
Prasad didn't cite anyevidence that Coadminister
is not safe or effective.
Rather, he said that he isn'tpersuaded by the evidence
supporting it, and he saidthat that evidence is based on
non-inferiority studies withconfidence intervals that he
(16:59):
thinks are too permissive.
the interesting thing is,is that CDC and a number
of academic groups havelooked into the same issue.
They've conducted studies,and the studies that they've
conducted according to CDC,American College of Physicians,
infectious Disease Society ofAmerica, show that it's safe
and effective to coadministerthe COVID vaccines with
(17:21):
the flu and RSV vaccines.
So kind of Pfizerdodged a bullet there.
It remains be seen whatthe impact of is gonna
be on the seasons uptakeof flu and, RSV vaccines.
It's a whole lot moreconvenient for people to get
them all at one time than itis in three different times.
(17:41):
I think that uptake of theCOVID vaccines gonna be
extraordinarily low thisyear anyway, for a variety of
reasons, including the narrowedindication that FDA is approved.
Okay, so then you say, well,what's the bigger picture?
Right.
So the bigger picture is thatPrasad made it clear that his
concern about co-administrationisn't limited to COVID vaccines.
(18:02):
FDA Commissioner Marty Makary,HHS Secretary Robert F.
Kennedy Jr. Have repeatedlysaid that they're skeptical
of the childhood vaccineschedule, that they don't
believe children need as manyvaccines as they receive,
and that the vaccinationshould be spaced out.
So Prasad's policyof questioning the
co-administration of vaccinescould be invoked to support
(18:24):
changing the vaccine scheduleand even forcing companies
to reformulate combinationvaccines such as the measles,
mumps, and rubella vaccine.
This has been agoal of anti-vaccine
advocates, includingKennedy for a long time.
I think if it does happen, itwould've catastrophic effects.
Instead of going to the doctorthree times over 12 to 15
(18:45):
months, parents would haveto go a dozen or more times.
I think it's likely that alot of parents wouldn't do
it, even if parents did do it.
and even if the systemcould kind of withstand
the added burden on,pediatricians to do this.
Kids would be vulnerableto the, pathogens that they
haven't been vaccinatedagainst for, you know, a
(19:07):
year or a year and a half.
And there have been studiesthat have, shown that failing
to coadminister, some of thevaccines, for example, with
measles exposed children,to, um, to measles and, and
actually resulted in outbreaksof measles because they hadn't
gotten co-administration.
Simone Fishburn (19:25):
Okay.
Steve.
let me just dial back a minute.
So what I'm hearing you sayis that Prasad doesn't like
the evidence that the peopleunder him or currently under
him have used to authorizeor approve these vaccines in
their current f ormulationsor co-administration
(19:48):
with other vaccines.
So evidence was lookedat by people at FDA and
they approved it, right?
And now he's coming in andsaying, well, I don't like that.
I'm not convincedby the evidence.
how is that different than whenhe was saying beforehand that he
didn't really like Peter Marksoverruling the people under him.
Steve Usdin (20:08):
Well, you know, I, I've said it a bunch
of times since January.
The hypocrisy ship in Washingtonsailed a long time ago, and
I don't think you're gonnaget very far by pointing
out inconsistencies and, andhypocrisies in public policy.
But I will say that you'reright that, um CBER had
concluded that it was safe tocoadminister safe and effective
(20:31):
to coadminister, COVID vaccinesand flu and RSV vaccines.
you may recall that when COVIDvaccines were first received,
emergency use authorization,FDA said that out of an
abundance of caution that theyshouldn't be co-administered
with other vaccines.
And then they came backlater and said, that
it's okay to do it.
(20:52):
And CDC and other groupsactually encouraged
this co-administration.
So yeah, and Prasad doesn'treally, provide any data
except his own personalskepticism to support this.
Simone Fishburn (21:03):
Well, that's what I wanted to drill down
on a little bit, becauselet's go from there to the
other things you talked about.
I don't know if Prasad, beforehe joined FDA, had raised
alarms on these kinds of issues.
But you know, there's onething where, a new leader
comes in and says, goingforward, this is how we're
(21:23):
gonna look at certain data.
This is what we're goingto do, this is what
we're going to require.
But how common is it forsomebody to come in and
say, I just wanna reevaluatethe way we did everything.
I don't like the way the oldFDA was t reating statistical
analysis or whatever thebasis is, and so I'm gonna
undo previous decisions.
Steve Usdin (21:44):
That's extraordinarily.
Uncommon.
And when it's done, when FDAchanges its policies in the past
that's been done through a kindof scientific consensus that's
been developed, its best whenit's developed in public, when,
um, they can get input from theentire scientific community as
well as, patients and other kindof stakeholders for doing it.
(22:07):
What isn't common whati s extraordinary is to
have a center director.
second guess the decisions that,FDA staff have made and say,
no, we're changing the policy.
And, and the FDA staffessentially learn about it
from the decision memo thatsenate director issues, as you
know, Peter Marks, did it, uh,there were a few instances of
(22:29):
doing him, doing that in thepast that was about specific.
Product, approval decisions.
it wasn't kind ofphilosophically, turning
the, the policy ship around,on something that's gonna
affect a whole class ofproducts, like vaccines.
Simone Fishburn (22:44):
So one more thing and humor me.
You know, I've been away.
I've been at a nephew'swedding in the U.K. and
having a very chill time,not getting all upset about
these kinds of things.
And I come back and I see thatthe CDC has kind of imploded.
and at the end of the daywhat really happened there is
a, a few people just sort ofput their foot down and said,
no meaning no, they'll walkout, is how I understand this.
(23:08):
The agency, I dunno what thefuture is of that agency.
So do you think there's gonnabe a ripple effect, Steve,
from CDC into FDA, maybeeven into NIH to a degree
are the goings on within eachof these agencies, which all
report obviously into HHS.
To what degree do you think theyspell from one end to the other?
Steve Usdin (23:28):
I would say that it is part of a coordinated
effort that's being led byRobert Kennedy Jr. to upend
disrupt, the vaccine, policy,of the United States and the
things that are happening atCDC, at FDA, and at NIH are all
(23:48):
part a coordinated effort, andit's not conspiracy thinking.
Simone Fishburn (23:52):
Well, I, I think that been
open about not a secret.
what I, I guess what I'masking is, is there a point
at which people just arelike, I can't support this
anymore, I'm outta here.
And publicly, I mean,we've obviously know that
a whole bunch of peoplehave gone privately and
do you think there's atipping point, is what I'm
Steve Usdin (24:10):
Yeah, we've, we've passed the tipping
point and I would disagreewith you a little bit.
I don't think the CDC imploded.
I think it was exploded.
So there's a little, a littlebit of a difference there.
We, we've seen it already.
at FDA, of course, ousting,Peter Marks, was part of that.
there have been other officials,the official who was in charge
of, biostatistics and postmarket pharmacovigilance at
(24:34):
CBER was pushed out of hisposition by Vinay Prasad and,
and forced to take a detail atCDER at the Center for Drugs.
And Vinay Prasad has madehimself acting, head of
that division at CBER.
There's a lot of othermachinations that are going on.
There are other peoplewho have been fired,
who have quit and so on.
So, at least when it comes to,um, to vaccines, we've certainly
(24:58):
gone past that tipping point.
And, we're heading,in a direction which.
I believe and I think, mostpublic health experts believe,
is troublesome and dangerous.
Simone Fishburn (25:07):
I mean, I, I actually wanna make
a, a. A point here forour listeners, which is.
Regardless of people's politicalopinion, we try very, very hard
BioCentury to tell it straight.
We, look for the science-basedalternative argument that
could support something.
I know that there are somepeople who will say, great
(25:28):
things are happening at FDAand certain interactions
with biotechs and things.
But I think that just whatwe're seeing on the vaccine
front alone in terms ofscientific, orthodox, or
scientific rigor, really, reallyhard, you know, this is not
necessarily a party politicalthing, really, really hard.
At some point you've just gottastand up and say, this is wrong.
(25:48):
It's just not possible forus to find a science-based
approach that supports this.
Where are we going now, Jeff?
Jeff Cranmer (25:59):
let's, um, hey, let's, uh, let's
talk about Medicare.
Um, there we go.
Steve, uh, you've been digginginto the, uh, effects of
changes to the Medicare drugnegotiation program, that were
included in that tax and budgetbill Congress passed in July.
(26:19):
What have you found?
Steve Usdin (26:20):
So.
that bill, which, you know,which people call the Big
Beautiful Bill, it includedan expansion of the orphan drug
exemption from the MedicareDrug Price Negotiation Program.
you recall the original bill,the IRA, that created the
price negotiation program,created an exemption for
orphan drugs, but was onlyif a drug had a single
(26:43):
orphan designation that itwas exempt from the IRA.
That had a lot ofunanticipated consequences.
it led, to companies sayingthat they were abandoning some,
orphan indications because theydidn't want to have a second or
a third, orphan indication thatwould, then trigger, Medicare
drug price negotiations.
(27:04):
Some big pharmassaid that they were.
Deprioritizing, orphan cancerindications, in favor of, more
common indications and so on.
So there were a lot ofunintended consequences
as a result of that.
Now, what in the, in the newlegislation, what they've
done is they've said, okay,if a drug only has orphan
(27:24):
indications, regardless ofthe number, it's exempt, from
Medicare drug price negotiation.
if its first indication isan orphan indication, if it's
subsequently later, you knowif it later gets a non-orphan
indication, the timing forwhen it's eligible for Medicare
drug price negotiation.
(27:45):
That clock starts ticking withthe first non-orphan indication.
So, limiting the exemptionin the original law, kind of
instantly and unintentionallydestroyed one business model for
rare disease, drug development.
And this model manufacturespieced together multiple
small indications thatare each too small to
(28:07):
justify investments in R&D.
What they do is they pursuemultiple small indications, put
together a package of them, inthe expectation that altogether,
there'll be enough return on,on the drug to justify the R&D.
This is good for, for those,small companies that do that.
It's typically small companiesand of course, it's very
(28:28):
good for the patients whohave those orphan diseases.
So in broadening the orphanexemption, Congress has
again made that businessmodel viable again.
The other thing that it's donethough, and by all accounts,
this was unanticipated by, mostof the, uh, lawmakers who were
(28:48):
working on this and also, bythe companies that were, pushing
for this, um, change in the law.
It's gonna delay pricenegotiations for some
blockbuster drugs.
The most obvious examplesare Keytruda from Merck and
Opdivo from, Bristol Myers.
Both of those drugs werefirst approved for an orphan
(29:08):
indication, and then a yearlater they were approved
for non-orphan indications.
That means that the firstdate that they're gonna be
eligible for Medicare drugprice negotiation has been put
back, by a year for each ofthose, I've got a story that's
coming out this week describingother examples of drugs, that
are gonna have delayed pricenegotiation and also that may
(29:32):
never be subject, to pricenegotiation because they have
multiple, orphan indications.
And as long as theirmanufacturers don't, get
approval for, non ORPindication, then they
will be exempt from pricenegotiation, forever.
The other thing that I'd saythat, that that's interesting
that's happened as a resultof this change is you're very
likely, we're very likely tosee, changes in the pipeline
(29:56):
prioritization of pharmas.
they're gonna shift back,to, the pre, IRA model where
they're gonna go first, um,with orphan indications,
especially for cancer drugs.
there's gonna be a temptationto either only have orphan
indications, in which case yourdrugs would never be subject
to the, uh, Medicare drugprice negotiation or to, push
(30:18):
off the non-orphan indication,until later in the drug's,
lifecycle so that you couldget, you can extend your, your
runway before negotiations.
one final thing here.
That's interesting.
It's another kind ofunintended consequence of this.
So I think that we're gonnasee, to an extent this supports
higher launch prices, right?
(30:39):
Because if a drug launchesfirst for an orphan indication,
typically pricing is higher andthe manufacturers justify that
higher pricing because, there'sgonna be a limited market.
It's an orphan market, right?
Then when they get anon-orphan indication,
here's what doesn't happen.
What doesn't happen typicallyis the manufacturer looking
at it and saying, oh, now I'vegot a non-orphan indication.
(31:01):
I've got a much bigger market,so I'm gonna lower the price.
that just isn't a thing.
so these are all kinds ofthings to, to think about.
Jeff Cranmer (31:08):
all right Steve.
Thanks for that update.
Out for Steve's storyon BioCentury dot com.
And if you're liking what you'rehearing, subscribe, follow us.
leave us a review.
We'd love to hear from you.
And Simone, youdidn't mention that.
Uh, in addition to the buzz cut,Your man Alcaraz is going for
(31:30):
a hot pink sleeveless top withpurple shorts and purple shoes.
And, uh, I gottasay, Wimbledon, uh,
organizers take note.
A little more colorful,little more colorful.
All right, well, we'll beback with our sister podcast
later this week, Steve andSimone, digging deep into
(31:51):
our back to school issue,we'll see you next week.
Thanks for tuning in.
And we appreciate KendallSquare Orchestra, which
produces the music for allof BioCentury's podcasts.
[AI-generated transcript.]
Jeff Cranmer (00:01):
Two of biotech's biggest names are bringing
the disease interception modelto cardiovascular risk with a
startup that's made its debuttoday, we'll discuss Corsera
from John Maraganore andClive Meanwell on the latest
BioCentury this week Podcastplus FDA has been quietly
(00:26):
positioning itself to disruptthe childhood vaccine schedule.
We'll hear the latest from ourWashington editor, Steve Usdin,
on what is happening at FDA aswell as changes to the Medicare
Drug Negotiation program.
And we have Simone back andshe has been dedicated to her
(00:51):
US open viewing and she'llgive us an update on the big.
Coco Naomi Showdown.
That happened over in, wheredo they hold that thing?
Queens, Brooklyn.
Who knows?
I got a bone up on my tennis.
I'm Jeff Cranmer, executiveeditor here at BioCentury
(01:11):
and host of the BioCenturythis week podcast.
And joining me today are
Simone Fishburn (01:16):
Simone Fishburn, Editor in Chief.
Steve Usdin (01:18):
Steve Usdin, Washington Editor.
Paul Bonanos (01:20):
And Paul Bonanos, Director of
Biopharma Intelligence.
Jeff Cranmer (01:24):
All right.
Thanks for joining me peeps.
Two veteran biotech leaders,are launching a new company
with ambitions in the CVdisease space, you talk to them.
Paul, tell us what you learned.
Paul Bonanos (01:38):
Sure.
so yeah, the story broke thismorning and I had a chance to
catch up last week with JohnMaraganore and Clive Meanwell,
you mentioned them both.
obviously both havebeen around a long time.
I think most people know, uh,John was co-founder and CEO of
Alnylam led the company for avery long time before handing
off his roles a few years ago.
And Clive was CEO of theMedicines Co. which Novartis
(02:00):
acquired for about $10billion a few years back.
So, um, these two peoplehave worked together before.
the Medicines Co. buyoutcentered on a drug we
now know as Leqvio alsoknown as inclisiran.
That targets PCSK9 totreat high cholesterol.
It originated with Alnylam,Medicines Co. licensed it,
and now it's Novartis to sell.
(02:21):
there's also aconnection further back.
Uh, going back to 1997,Maraganore was an inventor
of, uh, a thrombin inhibitorAngiomax, AKA bivalirudin,
which Medicines Co. broughtto market via partnership.
So what they're up tonow, they've launched a
cardiovascular health startupcalled Corsera Health.
And it has two things going on.
(02:42):
One is a dual acting RNAItherapy that, also targets
PCSK9, like inclisiran, alsotargets angiotensinogen to
treat high blood pressure.
you may recognize the secondtarget from another Alnylam
program, zilebesiran, that'sin late stage clinical testing.
Corsera 's, program is headedinto the clinic this year.
(03:04):
The other thing they have isa risk evaluation tool that's
intended to identify people whoare more likely to develop CV
disease and find them earlierin life, rather than sort of
wait for them to get diagnosed.
It's a software tool.
It uses AI in some component.
We didn't get too far intothe details of how the
software works, but, Johndescribed it as an algorithmic
(03:24):
tool that assesses riskof developing CV disease.
it's not a diagnostic, andjust to be clear, it's not a
companion diagnostic that goeswith the therapy, but it's
a way to figure out early onhow much risk a person has
of developing CV disease andthen the person and their
doctor can come up with atreatment strategy, which.
You know, may, may or may notinclude Corsera 's therapy.
(03:46):
and this is, you mentionedin the category of
disease interception.
We've written aboutthat before, some too.
Simone Fishburn (03:52):
Let me ask you about that and maybe ask
Steve as well, because I thinkit's, likely that we are just
gonna see more and more oftools like these AI tools maybe
launched along with a company.
Now you pointed out that thisis not a companion diagnostic.
So Steve, do regulatorscare about this?
Is this something thatjust exists only in
(04:14):
the commercial space?
how do you look at that?
Steve Usdin (04:17):
regulators do care about it.
Regulators around theworld have not just FDA are
trying to get their hands,their arms around, those
kinds of tools and to thinkabout how to regulate them.
you know, the, thepotential is enormous.
and the, um, the challengesare also substantial because
if you think about it.
Unlike just about any otherproduct, it's protean, right?
(04:38):
It's gonna keep changing theAI changes as it learns more.
So how do you, how doyou regulate something
that isn't gonna be thesame two days in a row?
that's a challenge.
I think a lot of the regulationaround it is going to depend
o n the kinds of decisionsthat are made based on it,
I think regulators aroundthe world, they're, they're
(04:59):
settling on a, a risk-based, uh,different kinds of risk-based
frameworks for these AI tools.
where the, the amount ofregulation and the amount
of scrutiny, is going tobe highly dependent on the
consequences of the decisionsthat are made based on them.
and there's also gonna haveto be an ongoing, monitoring
of safety issues, both by thecompanies that, manufacture
(05:22):
that, that make the AI toolsand by, providers that use them.
it's, we're gonna see alot more of this and we're
gonna see a lot more kind ofexperimentation around the world
about regulatory frameworksfor those kinds of tools.
Simone Fishburn (05:37):
Paul, you know, I have a question for you
as well, because you know JohnMaraganore, we've spoken to
him obviously over the years,and he's been one of the.
Forward thinkers really in termsof pricing models innovative
pricing models, sorry.
Wondering whether he talkedto you about the payer aspect?
I'm assuming that he believesthat payers will want this
(05:59):
kind of information and is thatpart of the company's thesis?
Paul Bonanos (06:04):
Well, it, it's, I should mention,
they, they stress that thereis no business model yet
around the tool, the AI tool.
and on the, on the therapeuticside, the path is much
more, um, well-defined.
it's not clear yet how it willshake out for reimbursement.
I would say.
Um, it is not unprecedentedas well, though we should
(06:24):
mention, Provention Bio andTzield teplizumab, which is
the, approved therapy to delayonset of type 1 diabetes.
And I think it's been prettyclear that that that there is a
market for something like that.
It may just be a veryslow growing one.
that's a, a therapy that Sanofipaid $2.9 billion, to acquire
(06:46):
and sales of the product arenow, in the first half of this
year, were 29 million Euro,about 33, 34 million U.S.
so there is a path to marketfor a disease interception for
people who aren't sick yet.
But, I don't think it'sclear, how reimbursement
will work for somethinglike Corsera 's therapy.
I'm drawing the comparison,but it's two very different
(07:07):
situations, right?
I mean, type 1 diabetes,delaying onset of type 1
diabetes is a much smallerindication than CV disease.
Pretty much the biggestkiller in the world, right?
so how, how far will people go?
How far will regulators orpayers go, to establish this
commercial path and for whom?
and it's up to the companyto, sort of make the market
(07:29):
and create the marketfor something like this.
It's, it's very differentfrom treating disease
that already exists.
Simone Fishburn (07:35):
So just one last word, Paul,
about the therapy itself.
Is this effectively goingto now be a competitor
to inclisira to Leqvio?
Paul Bonanos (07:45):
could be.
Yes.
Um, and the idea is to simplify,by, instead of having two
administrations to have one.
It could be competitive.
Obviously the timelines arequite different, Leqvio being
on the market and, um, this onejust now entering the clinic.
and it's also not clear whetherthis will be chiefly prescribed
to people to stave off diseaseor, to go to people who are
(08:07):
already, entering cardiovasculardisease later in life.
Jeff Cranmer (08:11):
All right, thanks for that, Paul.
Uh, Paul's story.
The latest in our emergingcompany profile series is
up on BioCentury dot com.
You can also find it at the linkin the show notes and we are
gonna take a quick break andthen we'll be back to talk about
(08:31):
what is going on in Washington.
Alanna Farro (08:34):
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Grand Rounds, BioCentury'sR&D conference, will make
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Jeff Cranmer (09:17):
Well, it is back to school time at
last on the U.S. East Coastand for us at BioCentury
for the past 33 years.
That means publishing oursignature issue of the year, and
that is called Back to School.
It's a forward lookingpackage that looks at a
(09:37):
broad issue, critical tothe biopharma industry.
And this year,Steve, one man show.
Well, of course you hadsome, uh, crack editors.
Steve, give us a quick teaser.
Steve Usdin (09:48):
Basically what I did this year is I said,
look, imagine that you'restarting with a blank sheet
of paper and you're creatingan optimal medical products
regulator for the United States.
How would you go about doing it?
and I and I talked to a lotof people at FDA, former FDA
people, CEOs of biopharmacompanies, academics.
(10:09):
And came up with, aprescription and, and I'll
be the first person to saythat it, it isn't definitive,
it isn't the last word.
It's really intended to spark adiscussion, a debate about, how
FDA, should be, reorganized.
couple of the points thatI make, I suggest that,
FDA's medical product.
Function should be separated,from its other functions.
(10:32):
In other words, what's now theCenter for Biologics, the Center
for Drugs, and the Center forDevices should be separated
from tobacco, cosmetics,veterinary products, And I
also suggest that the medicalproducts regulation should be
oriented and should be organizedaround, clinical, outcomes
(10:53):
around clinical functions.
and suggest that the OncologyCenter of Excellence should be a
model for how, medical productsregulation in the United
States should be organized.
As you said, it's a big package.
There's seven stories,there's a lot more to it.
I hope that, um, listeners, takethe time to read the package,
respond to it, think about it.
You'll also have the opportunityto, um, listen and watch, Simone
(11:16):
and I talk about it on TheBioCentury Show later this week.
Jeff Cranmer (11:20):
And that is our sister podcast, available
in audio and video form onBioCentury's YouTube channel.
And we did do a. Back to schoola little differently this year.
traditionally, as I said,we really released it around
the U.S. Labor Day holiday.
this year we released itin mid August, and we will
(11:41):
hear from Simone in a letterfrom the editor this week.
and that will containlinks to all seven stories.
And of course, you'llhave the podcast.
As well.
Now, this time of year isalso a, uh, time of year,
very special, to Simone,the U.S. Open, happening in
Flushing Meadows, New York.
(12:03):
I always get a vision of HomerSimpsons trip to Manhattan
and, the greater New York areawhere he, uh, wanders through
Flushing Meadows and it's, uh.
It's a really iconic scene.
But, Simone, uh, Skinner, theJoker, Alcaraz, who do you think
is gonna take it this year?
Simone Fishburn (12:22):
Sinner, I
Jeff Cranmer (12:24):
Si Sinner.
Simone Fishburn (12:25):
Yeah, yeah.
Yeah.
So, um, you
Jeff Cranmer (12:27):
that's that's 'cause Principal
Skinner on Simpsons it.
Sorry.
It was a little slipped there.
So.
Simone Fishburn (12:32):
so, you know, I always try to find like a,
a theme that's relevant tobiotech and I think this year
I wanna go with resilience.
Okay.
So.
one of the standout matches wasNaomi Osaka against Coco Gauff.
Naomi Osaka you've got a rootfor her if only because she
(12:53):
has, as several others have.
She's had a child and comeback since then, which is very
difficult to do in tennis.
And Coco is a local favorite.
But you know, go to theresilience thing because to
really reach the top, you gottago through a lot of failures.
There's this very famouscommencement speech by
(13:13):
Roger Federer from last yearwhere he talks about, even
though he won like 80% ofhis matches, he won only 54%
of his points or something.
So there's a lot of lossand failure that goes on,
and I guess that's whatCEOs need to do and biotech
right now, they just need tokeep picking themselves up.
and going at it again.
I know that, Steve feels likethat a little bit as he watches
(13:36):
the FDA undergo massive changes.
that agency's gonna requirea little bit of resilience.
So I don't know if you guyswanna pick that up and add
the thread there, but youdon't get anywhere in our
industry without being ableto take a few losses and
then, uh, still pick yourselfup and keep going at it.
Jeff Cranmer (13:56):
Well, I, we will head there in a second.
I, I, I need to hear.
Your men's winner's gonna be?
Simone Fishburn (14:01):
Alcaraz.
Jeff Cranmer (14:02):
I love that man.
He's gotta watchthe hair grow back.
he did the buzz cut thing.
That's maybe it.
Maybe Steve, youneed the buzz cut.
Well, a lot of, a lot ofthe teenagers today, uh,
I can say as, uh, the,uh, father of 15-year-old
boy mullets have come backand, uh, I really question.
Simone Fishburn (14:20):
do you think at BioCentury we should
just give people a choice?
Mullet or buzzcut That's it.
Steve Usdin (14:24):
Well, the, idea of the, yeah.
yeah.
Well, the idea of the mulletis business in the front
and party in the back.
So when you're on Zoom,people won't even know if
you've got a, got a mulletif you do it properly.
Jeff Cranmer (14:36):
man.
When, when I was a kid it waslike mohawks and you know, you
could do the Robert Smith of theCure hair and all that stuff,
Simone Fishburn (14:43):
don't, don't even go there.
I'm, I'm like of the big hair,eighties and early nineties kind
Jeff Cranmer (14:48):
All right.
I I like it.
I like it.
Well, Steve, uh, a lotof talk last week about
the turmoil at CDC.
it was in the media spotlight,but, you know, as you, you were
mentioning to me, uh, sort ofa quieter but potentially more
consequential drama was alsounfolding last week at FDA.
(15:09):
Do you wanna tell us about that?
Steve Usdin (15:11):
Yeah, so, so like you say, you know, the
turmoil at at CDC firing thedirector, three top scientists,
resigning, it got a lot ofattention quite rightly.
so did, FDA's narrowingof the approvals of COVID
vaccines, but there's somethingthat was really important
that flew under the radar.
In his decision memo about thePfizer BTech COVID vaccine,
(15:33):
CBER Director, Vinay Prasadprecluded co-administration
of the COVID vaccinewith flu or RSV vaccines.
This was a big dealfor two reasons.
One affecting Pfizer andCOVID and the other, I
think potentially havingeven bigger impacts.
So before Prasad's decision.
CBER staff had given Pfizerthe green light to include
(15:56):
co-administration of fluand RSV on its label.
And the reason we know that,besides the fact that people at
FDA told me that is that Pfizerhas already printed labels
and inserted them in hundredsof thousands of cartons of
vaccines saying that, that thevaccine can be co-administered
with flu and RSV vaccines.
(16:17):
So Prasad's decision could haveforced Pfizer to rip open every
carton and replace the labels.
This would've disrupteddistribution just as
shipments were startingfor the fall season when
respiratory infection surge.
Pfizer got FDA to agreeinstead to the company,
sending letters to healthcareproviders, telling them not
(16:38):
to coadminister the vaccines.
And that letter'sposted on FDA's website.
Prasad didn't cite anyevidence that Coadminister
is not safe or effective.
Rather, he said that he isn'tpersuaded by the evidence
supporting it, and he saidthat that evidence is based on
non-inferiority studies withconfidence intervals that he
(16:59):
thinks are too permissive.
the interesting thing is,is that CDC and a number
of academic groups havelooked into the same issue.
They've conducted studies,and the studies that they've
conducted according to CDC,American College of Physicians,
infectious Disease Society ofAmerica, show that it's safe
and effective to coadministerthe COVID vaccines with
(17:21):
the flu and RSV vaccines.
So kind of Pfizerdodged a bullet there.
It remains be seen whatthe impact of is gonna
be on the seasons uptakeof flu and, RSV vaccines.
It's a whole lot moreconvenient for people to get
them all at one time than itis in three different times.
(17:41):
I think that uptake of theCOVID vaccines gonna be
extraordinarily low thisyear anyway, for a variety of
reasons, including the narrowedindication that FDA is approved.
Okay, so then you say, well,what's the bigger picture?
Right.
So the bigger picture is thatPrasad made it clear that his
concern about co-administrationisn't limited to COVID vaccines.
(18:02):
FDA Commissioner Marty Makary,HHS Secretary Robert F.
Kennedy Jr. Have repeatedlysaid that they're skeptical
of the childhood vaccineschedule, that they don't
believe children need as manyvaccines as they receive,
and that the vaccinationshould be spaced out.
So Prasad's policyof questioning the
co-administration of vaccinescould be invoked to support
(18:24):
changing the vaccine scheduleand even forcing companies
to reformulate combinationvaccines such as the measles,
mumps, and rubella vaccine.
This has been agoal of anti-vaccine
advocates, includingKennedy for a long time.
I think if it does happen, itwould've catastrophic effects.
Instead of going to the doctorthree times over 12 to 15
(18:45):
months, parents would haveto go a dozen or more times.
I think it's likely that alot of parents wouldn't do
it, even if parents did do it.
and even if the systemcould kind of withstand
the added burden on,pediatricians to do this.
Kids would be vulnerableto the, pathogens that they
haven't been vaccinatedagainst for, you know, a
(19:07):
year or a year and a half.
And there have been studiesthat have, shown that failing
to coadminister, some of thevaccines, for example, with
measles exposed children,to, um, to measles and, and
actually resulted in outbreaksof measles because they hadn't
gotten co-administration.
Simone Fishburn (19:25):
Okay.
Steve.
let me just dial back a minute.
So what I'm hearing you sayis that Prasad doesn't like
the evidence that the peopleunder him or currently under
him have used to authorizeor approve these vaccines in
their current f ormulationsor co-administration
(19:48):
with other vaccines.
So evidence was lookedat by people at FDA and
they approved it, right?
And now he's coming in andsaying, well, I don't like that.
I'm not convincedby the evidence.
how is that different than whenhe was saying beforehand that he
didn't really like Peter Marksoverruling the people under him.
Steve Usdin (20:08):
Well, you know, I, I've said it a bunch
of times since January.
The hypocrisy ship in Washingtonsailed a long time ago, and
I don't think you're gonnaget very far by pointing
out inconsistencies and, andhypocrisies in public policy.
But I will say that you'reright that, um CBER had
concluded that it was safe tocoadminister safe and effective
(20:31):
to coadminister, COVID vaccinesand flu and RSV vaccines.
you may recall that when COVIDvaccines were first received,
emergency use authorization,FDA said that out of an
abundance of caution that theyshouldn't be co-administered
with other vaccines.
And then they came backlater and said, that
it's okay to do it.
(20:52):
And CDC and other groupsactually encouraged
this co-administration.
So yeah, and Prasad doesn'treally, provide any data
except his own personalskepticism to support this.
Simone Fishburn (21:03):
Well, that's what I wanted to drill down
on a little bit, becauselet's go from there to the
other things you talked about.
I don't know if Prasad, beforehe joined FDA, had raised
alarms on these kinds of issues.
But you know, there's onething where, a new leader
comes in and says, goingforward, this is how we're
(21:23):
gonna look at certain data.
This is what we're goingto do, this is what
we're going to require.
But how common is it forsomebody to come in and
say, I just wanna reevaluatethe way we did everything.
I don't like the way the oldFDA was t reating statistical
analysis or whatever thebasis is, and so I'm gonna
undo previous decisions.
Steve Usdin (21:44):
That's extraordinarily.
Uncommon.
And when it's done, when FDAchanges its policies in the past
that's been done through a kindof scientific consensus that's
been developed, its best whenit's developed in public, when,
um, they can get input from theentire scientific community as
well as, patients and other kindof stakeholders for doing it.
(22:07):
What isn't common whati s extraordinary is to
have a center director.
second guess the decisions that,FDA staff have made and say,
no, we're changing the policy.
And, and the FDA staffessentially learn about it
from the decision memo thatsenate director issues, as you
know, Peter Marks, did it, uh,there were a few instances of
(22:29):
doing him, doing that in thepast that was about specific.
Product, approval decisions.
it wasn't kind ofphilosophically, turning
the, the policy ship around,on something that's gonna
affect a whole class ofproducts, like vaccines.
Simone Fishburn (22:44):
So one more thing and humor me.
You know, I've been away.
I've been at a nephew'swedding in the U.K. and
having a very chill time,not getting all upset about
these kinds of things.
And I come back and I see thatthe CDC has kind of imploded.
and at the end of the daywhat really happened there is
a, a few people just sort ofput their foot down and said,
no meaning no, they'll walkout, is how I understand this.
(23:08):
The agency, I dunno what thefuture is of that agency.
So do you think there's gonnabe a ripple effect, Steve,
from CDC into FDA, maybeeven into NIH to a degree
are the goings on within eachof these agencies, which all
report obviously into HHS.
To what degree do you think theyspell from one end to the other?
Steve Usdin (23:28):
I would say that it is part of a coordinated
effort that's being led byRobert Kennedy Jr. to upend
disrupt, the vaccine, policy,of the United States and the
things that are happening atCDC, at FDA, and at NIH are all
(23:48):
part a coordinated effort, andit's not conspiracy thinking.
Simone Fishburn (23:52):
Well, I, I think that been
open about not a secret.
what I, I guess what I'masking is, is there a point
at which people just arelike, I can't support this
anymore, I'm outta here.
And publicly, I mean,we've obviously know that
a whole bunch of peoplehave gone privately and
do you think there's atipping point, is what I'm
Steve Usdin (24:10):
Yeah, we've, we've passed the tipping
point and I would disagreewith you a little bit.
I don't think the CDC imploded.
I think it was exploded.
So there's a little, a littlebit of a difference there.
We, we've seen it already.
at FDA, of course, ousting,Peter Marks, was part of that.
there have been other officials,the official who was in charge
of, biostatistics and postmarket pharmacovigilance at
(24:34):
CBER was pushed out of hisposition by Vinay Prasad and,
and forced to take a detail atCDER at the Center for Drugs.
And Vinay Prasad has madehimself acting, head of
that division at CBER.
There's a lot of othermachinations that are going on.
There are other peoplewho have been fired,
who have quit and so on.
So, at least when it comes to,um, to vaccines, we've certainly
(24:58):
gone past that tipping point.
And, we're heading,in a direction which.
I believe and I think, mostpublic health experts believe,
is troublesome and dangerous.
Simone Fishburn (25:07):
I mean, I, I actually wanna make
a, a. A point here forour listeners, which is.
Regardless of people's politicalopinion, we try very, very hard
BioCentury to tell it straight.
We, look for the science-basedalternative argument that
could support something.
I know that there are somepeople who will say, great
(25:28):
things are happening at FDAand certain interactions
with biotechs and things.
But I think that just whatwe're seeing on the vaccine
front alone in terms ofscientific, orthodox, or
scientific rigor, really, reallyhard, you know, this is not
necessarily a party politicalthing, really, really hard.
At some point you've just gottastand up and say, this is wrong.
(25:48):
It's just not possible forus to find a science-based
approach that supports this.
Where are we going now, Jeff?
Jeff Cranmer (25:59):
let's, um, hey, let's, uh, let's
talk about Medicare.
Um, there we go.
Steve, uh, you've been digginginto the, uh, effects of
changes to the Medicare drugnegotiation program, that were
included in that tax and budgetbill Congress passed in July.
(26:19):
What have you found?
Steve Usdin (26:20):
So.
that bill, which, you know,which people call the Big
Beautiful Bill, it includedan expansion of the orphan drug
exemption from the MedicareDrug Price Negotiation Program.
you recall the original bill,the IRA, that created the
price negotiation program,created an exemption for
orphan drugs, but was onlyif a drug had a single
(26:43):
orphan designation that itwas exempt from the IRA.
That had a lot ofunanticipated consequences.
it led, to companies sayingthat they were abandoning some,
orphan indications because theydidn't want to have a second or
a third, orphan indication thatwould, then trigger, Medicare
drug price negotiations.
(27:04):
Some big pharmassaid that they were.
Deprioritizing, orphan cancerindications, in favor of, more
common indications and so on.
So there were a lot ofunintended consequences
as a result of that.
Now, what in the, in the newlegislation, what they've
done is they've said, okay,if a drug only has orphan
(27:24):
indications, regardless ofthe number, it's exempt, from
Medicare drug price negotiation.
if its first indication isan orphan indication, if it's
subsequently later, you knowif it later gets a non-orphan
indication, the timing forwhen it's eligible for Medicare
drug price negotiation.
(27:45):
That clock starts ticking withthe first non-orphan indication.
So, limiting the exemptionin the original law, kind of
instantly and unintentionallydestroyed one business model for
rare disease, drug development.
And this model manufacturespieced together multiple
small indications thatare each too small to
(28:07):
justify investments in R&D.
What they do is they pursuemultiple small indications, put
together a package of them, inthe expectation that altogether,
there'll be enough return on,on the drug to justify the R&D.
This is good for, for those,small companies that do that.
It's typically small companiesand of course, it's very
(28:28):
good for the patients whohave those orphan diseases.
So in broadening the orphanexemption, Congress has
again made that businessmodel viable again.
The other thing that it's donethough, and by all accounts,
this was unanticipated by, mostof the, uh, lawmakers who were
(28:48):
working on this and also, bythe companies that were, pushing
for this, um, change in the law.
It's gonna delay pricenegotiations for some
blockbuster drugs.
The most obvious examplesare Keytruda from Merck and
Opdivo from, Bristol Myers.
Both of those drugs werefirst approved for an orphan
(29:08):
indication, and then a yearlater they were approved
for non-orphan indications.
That means that the firstdate that they're gonna be
eligible for Medicare drugprice negotiation has been put
back, by a year for each ofthose, I've got a story that's
coming out this week describingother examples of drugs, that
are gonna have delayed pricenegotiation and also that may
(29:32):
never be subject, to pricenegotiation because they have
multiple, orphan indications.
And as long as theirmanufacturers don't, get
approval for, non ORPindication, then they
will be exempt from pricenegotiation, forever.
The other thing that I'd saythat, that that's interesting
that's happened as a resultof this change is you're very
likely, we're very likely tosee, changes in the pipeline
(29:56):
prioritization of pharmas.
they're gonna shift back,to, the pre, IRA model where
they're gonna go first, um,with orphan indications,
especially for cancer drugs.
there's gonna be a temptationto either only have orphan
indications, in which case yourdrugs would never be subject
to the, uh, Medicare drugprice negotiation or to, push
(30:18):
off the non-orphan indication,until later in the drug's,
lifecycle so that you couldget, you can extend your, your
runway before negotiations.
one final thing here.
That's interesting.
It's another kind ofunintended consequence of this.
So I think that we're gonnasee, to an extent this supports
higher launch prices, right?
(30:39):
Because if a drug launchesfirst for an orphan indication,
typically pricing is higher andthe manufacturers justify that
higher pricing because, there'sgonna be a limited market.
It's an orphan market, right?
Then when they get anon-orphan indication,
here's what doesn't happen.
What doesn't happen typicallyis the manufacturer looking
at it and saying, oh, now I'vegot a non-orphan indication.
(31:01):
I've got a much bigger market,so I'm gonna lower the price.
that just isn't a thing.
so these are all kinds ofthings to, to think about.
Jeff Cranmer (31:08):
all right Steve.
Thanks for that update.
Out for Steve's storyon BioCentury dot com.
And if you're liking what you'rehearing, subscribe, follow us.
leave us a review.
We'd love to hear from you.
And Simone, youdidn't mention that.
Uh, in addition to the buzz cut,Your man Alcaraz is going for
(31:30):
a hot pink sleeveless top withpurple shorts and purple shoes.
And, uh, I gottasay, Wimbledon, uh,
organizers take note.
A little more colorful,little more colorful.
All right, well, we'll beback with our sister podcast
later this week, Steve andSimone, digging deep into
(31:51):
our back to school issue,we'll see you next week.
Thanks for tuning in.
And we appreciate KendallSquare Orchestra, which
produces the music for allof BioCentury's podcasts.
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