FDA Direct Ep. 6: FDA is Not Your Doctor – Discussing FDA's Role and Mandate

OK, we're doing this unscripted,
unfiltered,

sometimes a little clumsy as a result,
but here we are.

Good to see you, Vinay.

Good to see you, Sanjula..

So it's good to be back here.

Yeah.

Good to have you.

A beautiful day.

Beautiful day here.

Enjoyed the farmers market today,
which was awesome.

It's great.

I went twice, got coffee,
and then I got lunch.

It's getting bigger.

Hopefully we're going to do it multiple
days of the week.

The whole campus is out there.

Everyone's happy to go to that farmers
market.

Everyone's happy.

And we are hiring scientific reviewers
and inspectors.

Job positions are getting posted.

So for all the people who love doing
science, come on over to the FDA.

Little shameless plug.

Great.

Well,
I have some questions I was hoping we can

get into.

There's been a lot of buzz and kind of
questions around.

I think you ,
we just approved a new vaccine out there.

Oh yeah.  Moderna's new product mNexspike.

Yes, FDA gave it marketing authorization.

OK yeah.

And so how is that different than
existing COVID vaccines?

Moderna had a previous product called
Spikevax,

and the difference between Spikevax and
mNexspike is instead of going after the

entire spike protein,
they've got 2 smaller pieces of the spike

protein that they've decided to target in
their new vaccine formulation mNexspike.

And the FDA,
consistent with what Marty and I were

saying in the New England Journal of
Medicine,

have given them a marketing authorization
for 65 and older and then people at high

risk of severe COVID-19 outcomes.

And the company is committed to doing the
randomized control trial,

placebo-controlled randomized study that
we want them to do.

Love it.

OK.

So just to make sure I got all that.

So it's a different product.

It's a different product.

OK.

But for the same disease.

For the same disease, COVID-19.

Yeah.

And so what does that mean for existing
versions of the vaccine?

Like,
there's just another option for consumers?

Well,
I guess Moderna is probably best to tell

you what their broader game plan is with
these two things.

But right now,
they have two approved products.

They have Spikevax,
and they have mNexspike.

And I think in the years to come,
we will see the direction the company

chooses to move in.

But what does it mean?

I think it means realistically.

Realistically,
we're in the summertime right now.

I personally don't know too many people
who are going out and getting vaccinated

right now.

There are still a few people,
but I don't know too many of them.

Mostly people are waiting for what's
going to happen in the fall.

Very likely we're going to be in a
situation where there are at least three

companies bringing products to market,
Novavax with the product that we approved

a few weeks ago, which targets JN.
1 and then Moderna and Pfizer that may

target  a JN.1 sub lineage.

We'll learn more about that by the fall.

What is JN.1?

What is JN.1?

Good question.

So as you know,
throughout the COVID-19 pandemic,

this virus has been changing.

In the beginning, it was extremely lethal,
put a lot of people in the hospital.

Over time, it evolved in different ways.

There was a Delta way,
which is really sort of bad a few several

winters ago.

And then finally it rested on this
Omicron subvariance or JN.1,

just a fancy way of talking about the
genomics and,

and sort of the nature of the virus.

And,
and it has really been stuck on this JN.

1 kind of strain for at least two
calendar years now.

I mean,
that's what the WHO and the FDA said two

years ago.

Think about JN.1 and JN.
1 sub lineages like KP2.

And again this year we're saying JN.
1 and sub lineages like LP.8.1.

So what is it?

It's a it's a, it's a type of coronavirus,
a strain that is the dominant strain

that's taken hold of the globe.

OK.

And so you mentioned something about the
RCT.

Can you just unpack a little bit more?

So to approve this drug,
we did not require an RCT upfront,

is that correct?

Well,
the company did do randomized controlled

trials,
but they tested their new product and

mNexspike against their older product
Spikevax.

And we at FDA felt that that was
sufficient to allow this product to be

available to the vulnerable people,
older people and high risk people.

But as we have said all along,
and we're going to stick to and they are

going to fulfill their commitments.

We want to see a randomized control trial
of people between 50 and 64 who are

healthy Americans to show me these
vaccines are doing what we hope they're

doing and what we think they might be
doing.

But we don't know for sure.

And we want to see that in this age group
where there's something what we call

global equipoise,
means that people across all the

countries in the world,
people are genuinely unsure if the

vaccines work in that age group.

Some countries recommend it, some don't.

We want to see proof that it works.

And again,
they're not going to go up against

another Moderna product in this study.

It's Moderna vaccine against a saline
placebo.

We're going to see all the adverse events
in this study.

We're going to see whether or not it
helps people and what it does and whether

or not it's working like we think it
might be in 2025.

You know,
I think a lot of people are going to be

interested in the results of that trial
because I think it's an honest unknown.

It's a scientific unknown.

And so when you get into that group that
you describe the 50 to 65, I mean, France,

you got to be 75 or 80 actually 80 in
France, 75 in the UK or high risk.

I think a lot of clinicians,
a lot of moms,

a lot of people out there in the world
are wondering,

does the risk benefit ratio favor getting
it at this point?

So I think a lot of people are going to
be interested in that results.

I mean, let's be honest,
the numbers suggest there's either a lot

of skepticism, uncertainty, distrust,
but 85% of healthcare workers did not get

the last COVID shot and somewhere between
12 and 13,

12 and 14% of kids got the last COVID
shot.

So that means for 87, 88% of parents,
for eighty, 87, 88% of kids,

their parents said no,
thank you to the last COVID shot.

So I think you're going to answer some
really interesting questions.

It's such a key study.

And I think there's another misconception
I want to clarify,

which is people have said you at FDA are
recommending the shots to high risk

people and, and, and older people.

I want to be very clear,
the FDA is not your doctor.

We are not,
we don't recommend shots to people.

What we do is we make them available for
patients to have a conversation with

their doctor.

But I can understand a 66 year old who
goes to see their doctor and they may

decide to do it or not do it.

That's their medical decision.

FDA is granting a marketing authorization
for that.

But we are not in the business of making
recommendations.

That's other agencies and other bodies.
MNexspike is now available to 65 and up

or people at high risk of COVID-19.

They're going to run a randomized study
in this population where you have genuine

uncertainty and the results of those
study,

that study and other company studies will
be available.

I'm optimistic by the planned dates by
the spring and summer of 2026 and then

the entire medical community is going to
be able to look at those results and our

thinking will evolve.

We will learn something that we have not
learned in four plus years,

which is what are these vaccines doing in
a elegant randomized control trial.

I think it's a,
it's a really good point that the

physician patient relationship is really
sacred.

And when the government tries to become
your doctor,

we don't have a great track record.

We do not have a good track record.

And I think some people look look to the
government and health agencies to

adjudicate on every single aspect of
their life and lifestyle as it relates to

health.

We saw that during COVID when the
quarantine periods changed.

Is it 5 days, seven days, 10 days?

And then when I come out out of a
quarantine,

do I need to wear a mask if I'm
vaccinated?

And at this time of season of high risk,
low risk,

you can't possibly adjudicate on every
aspect of American life.

And so our job at the FDA is pretty
simple.

And that is we get applications and we
have a mandate from Congress to review

the data in those applications and decide
whether or not products are safe and

effective and for what group.

And you know, that's,
that's a really excellent point.

I've also heard some people say,
why don't you just make it available for

everyone six months in age and up.

And the truth is we have a mandate at FDA
and that's a that's a statutory mandate

that we need to have confidence the
benefits outweigh the risks.

And I cannot in good conscience,
and I don't think you can.

I don't think any of the reviewers here
can tell a 20 year old man who's had

COVID 4 times and had three or four or
five shots that they derive a net health

benefit from getting an additional fall
booster.

If we don't have that confidence,
we can't give those marketing

authorization.

That's our statutory duty at FDA.

Now I know this is a kind of a very
simple question and probably seems

obvious,
but I think it's worth unpacking what you

mean by benefit risk ratio.

Great point.

You know,
so I think that all medical products have

risks and some have benefits and some
have benefits that exceed the risks.

So what do I mean by that?

You know,
let's just take something like high blood

pressure.

High blood pressure can shorten your life
and we have a number of anti hypertensive

drugs that can lower blood pressure and
many of them have also been shown to

lower heart attacks and improve longevity.

High blood pressure pills also have side
effects.

Many people have had trouble with a high
blood pressure medication and we don't

give high blood pressure pills to people
with normal blood pressure,

we give it to certain high certain levels
of blood pressure.

I know there's a debate about you know
the specific cut offs used and some

randomized control trials like Sprint
that people are critical of,

but depends maybe 140 or 130, 125,
they're different high blood pressure

values above that.

We think the benefits are bigger than the
risks,

but we're not giving a person with 110
systolic a high blood pressure pill,

for instance.

And similarly,
all medical products are the same way.

We have cancer drugs we give to people
with a certain risk of bad cancer

outcomes,
but we don't give it to people at lower

stage or lower risk.

This is true across all aspects of
medicine.

Statin medications we give to people with
a certain LDL cholesterol or higher and

cardiovascular risk,
but not the people at normal LDL

cholesterol and cardiovascular risk.

COVID-19 vaccines are are thought of.

You know,
Marty talks about the two camps this this

blind booster in perpetuity camp thinks
that everyone should get one in

perpetuity.

That's not what medicine is.

Medicine is always about what's your
absolute risk of something?

What's the absolute benefit you might
drive?

And what are the risks that are known and
unknown?

And what's the balance of this?

And we can't answer that for every person
out there.

That's why there's a doctor for every
patient.

We just provide marketing authorizations
at FDA.

I really like your cancer analogy because
that resonates with me, right?

Like navigating family members through
that, right?

You know,
going in for these severe stages,

there may be some drugs that could work
or could not work,

but your physician explains to you what
those trade-offs are.

And so this is kind of similar where
we're going to be able to get that data.

If somebody has a colon cancer that's
removed,

they may get adjuvant chemotherapy or
several cycles of chemotherapy,

but that recommendation is going to be
different if they have stage 3 versus

stage 2 versus stage 1 colon cancer.

Sometimes we'll give two drugs,
sometimes we'll give it for six months,

sometimes we won't give any drugs at all.

So we always take into account the risk
to the person from the disease,

the potential benefit of the medicine and
the harms of the medicine.

That's just medicine 101.

And I think that's been lost in the COVID
discussion because naturally people have

just been piped the message of be fearful,
be fearful, be fearful.

And it's hard to continue to pipe that
message when we've been living with it

for five years.

Most of us have had it several times.

Some people say, well,
I haven't had it recently.

But the truth is they may not know
they've had it.

You know,
we're not even doing a great job of

documenting all the times you've had it.

They've also,
many people have also received one,

if not 2, if not three,
if not more doses of these products.

We just don't know for so many people
what the right number of boosters is.

I think we,
we lose that connection sometimes even in

tumor board where you'll see a CAT scan
and they'll be a tumor in a certain

location.

And we'll talk about the blood vessel
involvement and the sophisticated

operation that can be done or they,
you know,

preoperative radiation or the adjuvant
therapy.

But then the tumor board is over and you
go over and meet the patient and you

discover a frail old man who is not that
interested in treatment and has different

life goals.

And so, you know, you,
you realize like that disconnect between

a hard and fast recommendation versus
tailoring recommendation to an individual

based on their, their physiologic reserve,
their interest, their desire,

their life goals or ambitions.

Their I mean,
some people want to live forever and

other people feel like, you know,
I've had patients tell me I've had a good

run and I just don't want to go through
all this at this point.

It's so well said.

You know,
people call it personalized medicine and

they talk about genetics and all these
omics and molecular therapies,

but the truth is,
medicine has always been personal.

If you want to prescribe someone a pill,
if you want to do a surgery on them,

you have to look them in their eye.

You have to lay hands on the person.

You have to understand where they're
coming from,

their values and preferences and you
often get information in the doctor

patient encounter that you don't get from
the chart.

And nobody thinks medicine can be
practiced by the FDA,

the government practicing medicine here
in White Oak for every single person out

there.

I think that's part of the mistake here.

I think we in FDA have again struck a
very fair balance.

We're making these products available to
many,

many Americans who are at high risk of
these condition,

to the fraction of Americans who are
really worried.

We're also making the manufacturers
generate, I should say,

encouraging the manufacturers strongly to
generate data so that we can all learn to

whom these vaccines should be applied and
how many doses we should give.

I think, you know,
so from the econ perspective, right,

Thinking about costs,
another thing I've been hearing and

reading about is, well, you know,
based off how we approve things that

determines reimbursement, right?

And certain drugs may or may not be
covered.

But what's interesting is, you know,
when it comes to all,

you guys know this very well,
when it comes to oncology,

rare disease treatments,
a lot of these therapies are very

expensive and are not necessarily covered
by many insurance, you know,

companies and CMS.

So just because of what we do at FDA,
right, there's,

there's a different jurisdiction with
kind of the coverage.

This is a great point.

Well, first of all,
this man wrote a whole book about the

labyrinth processes of healthcare
coverage and who pays exactly what.

But just to be clear,
the FDA also is not allowed to consider

cost and to whom the costs are born in
our decisions.

But we do have a duty to to not approve
products when we are not sure the

benefits outweigh the risks.

That's our duty.

And we just can't rubber stamp a blind
boosters in perpetuity strategy for eight

for the next 10 years.

You know,
Marty says this all the time that an 8

year old girl if she lives till she's 80,
should she get 80 boosters in her natural

life?

We can't rubber stamp that in good
conscience.

That's not part of the duty of the FDA.

And I and I sort of hear in your voice
that we want to give people the benefit

of the doubt when especially when you're
talking about incurable conditions and

disabilities and conditions where there's
no other treatment of any,

any type of suffering is terrible and
obviously rare diseases.

We want to give people the benefit of the
doubt and tailor that regulatory process

for the condition being treated.

At the same time,
we don't want people to have false hope,

financial toxicity,
have their lives ruined financially and

take something that has known harm.

So we you know, it's not you know,
you can't approve 100% of drugs that come

through for these conditions just because
these people are dealing with terrible

suffering.

We have to adjudicate some good judgement
to give them the benefit of the doubt and

err on the side of giving people both the
spirit and the letter of right to try and

at the same time keeping an eye on safety
and factoring in other things.

Yeah, well, I mean,
you segue to rare disease.

So, you know,
we're going to have some discussions

later this week on that.

So I think it'll be good to come back
together and talk about, you know,

how are we thinking about some of those
parameters.

I think it's one of the reasons why we're
in this room today because the cameras,

we got a giant camera here.

People can't see it,
but few friends we have who are watching,

including Bigfoot over there.

Thanks for being here again.

There's a giant camera here and the
reason we're in this room is it was too

big to move to our regular spot because
there's so much going on at the FDA this

week.

We have infant formula.

We've got the Round Table with cell and
gene therapy Thursday that you're leading.

You're having your first CEO listening
tour session.  Our first listening, yeah,

our first CEO forum with executives of
drug developers.

So a lot going on and that's why we're
here in this room today,

which we're not normally in and we don't
have the beautiful background behind us,

but we can see it.

I think you made an interesting point
about regulatory flexibility and rare

diseases, which is that, you know,
we're talking about the COVID-19 vaccine,

we're talking about healthy people,
we're talking about 10s of millions of

people,
and we're talking about randomized

control trials.

And those things kind of make sense to me.

Healthy people taking a novel medical
product or a medical product year after

year, millions of people affected.

You need to do randomized control trials.

But in the rare disease space,
we're talking about sometimes conditions

where there's only 40 people with the
condition where we know that We know that

if they don't do something now,
they have a 50% mortality rate in two

years, something like that,
or they have severe disability.

We know that randomized trials are not
always feasible,

possible or practical in those situations.

And they're, we're, of course,
we're going to be much more forceful.

How can you not have empathy on that
group and want to try,

want to give them some opportunity when
they're willing to try, you know,

to take some risks?

For some hope.

Because their risk benefit ratio is
different.

Yeah, it's different.

And it's also unknown sometimes where if
we can generally guard against

Yeah, dangerous things.

If we can generally guard against that,
how can you not want to support that

endeavor?

And and there to to be clear,
we're still not the doctor.

We still don't tell each patient you have
to take this product.

What we're saying is it's available for
you and your doctor to decide if it's

right for you.

And you can imagine a situation where the
doctor says this is right for you.

And I believe you ought to give it a try.

Also a situation where the patient or
doctor says it's not right for me.

And that's again, not our purview.

So important and I,
I think if I remember correctly,

your Cell and Gene Therapy Roundtable.

Not only have experts and academics and
leaders from different sectors,

but I think some patients, friends,
patients.

And loved ones either who have loved ones
affected by rare disease.

Didn't you just speak it at one of those
meetings?

I was this morning,
I was at the NORD meeting,

which is the rare disease advocacy
organization,

and I gave a keynote address,
which was a great opportunity to kind of

convey our philosophy and our commitment
to expediting products for patients.

I'm sure they appreciated that.

They did.

I sent them your well wishes.

They appreciated that.

It's kind of the fun.

It's kind of one of the fun parts of the
job.

I didn't anticipate is you get a chance
to circulate here so many different

perspectives.

You know,
in this CEO forum sort of national tour,

we're asking for big ideas, you know,
giant ideas,

things that that people have always
thought,

why doesn't the FDA do it this way?

We want to hear those ideas.

And so bring it on.

For what it's worth,
I've been emulating that model internally

too,
as I've been meeting with different teams.

And so even just this morning I was
chatting with some of our economists and

I said, you know,
what are some ideas you have of things

you want to try or do differently?

And this, this individual said,
I hadn't thought about that.

Thank you.

Thank you for asking and let me get back
to you.

And so I think it's really exciting that
we're starting to really think about

these ideas both internally and
externally to see where we can make an

impact.

So this is a point that I think Marty
makes,

and it's sometimes underappreciated,
which is that.

The FDA is a terrific place,
and there are lots of people with

institutional memory who've worked here
10/20/30 or even more years.

And these people are invaluable because
they understand the history of the FDA in

ways that, you know, I don't.

But at the same time,
there's also a value in bringing in new

people who don't have that institutional
memory because they inject new ideas.

And they sometimes are the first people
to say, hey,

you've been doing this this way for a
long time,

but why don't you try it a different way?

And all great organizations need a mix of
the boat.

You need the people who've been there a
long time,

but also some new ideas once in a while.

How can you not want to come work here if
you're a scientist out here hanging out

with Vinay and Sangula,
you get a couple of those fresh bread

sandwiches at the farmers market.

I mean, it is, it is very attractive here.

And, and just so people know, to be clear,
we're not hiring scientific reviewers

because anywhere laid off people took
there's a retirement normal churn.

People leave because people move on to
other careers.

And so there is,
there are always openings.

And so we want to encourage people to
come to the FDA right now.

I'll give another plug for that,
which is that, you know, I've been,

I've been reading papers for 20 years,
you know,

20 years I've been reading every year I'm
learning something new,

a statistical technique I didn't know or
another way in which clinical trials are

run that I didn't quite appreciate.

In the four weeks I've been on this job,
I've learned 4X the number of things

because you get access to sort of the the
deepest level of thinking about how

clinical trials are run and how they're
analyzed.

We have access to a lot of the individual
patient level data in these clinical

studies.

Some of the statistical analysis here are
the most elegant I've ever seen.

I mean,
it's really the pinnacle of what it means

to read and understand.

Medical research is working at the FDA.
And you'll have to read a little less

because we have AI now.

They'll assess that transition.

So there's typically like thousands of
pages of background information in an

application.

And so the AI is identifying redundancies
in the background to say there's multiple

papers that say the same thing and
summarizing that.

And so it is making the job more
efficient.

So far,
I've heard great things from the staff,

I think.

When did it debut?

Today's the first full day.

I believe it launched yesterday, 2.
3000 scientists and people at the FDA

logged on.

Unique people logged on by 9:30 this
morning.

I think I got the update.

So people are using it and we're going to
keep making it better.

You know,
we can always benefit from multiple

iterations.

And it's more than just for viewers,
right?

It's, you know,
for our investigators who identify high

yield targets and a lot of different use
cases, we're going to start unpacking.

Pretty cool.

Yeah.

Exciting times.

Yeah.

Great.

And we have a busy week ahead,
so maybe we should land here and check

back in to work in the back in town from.

Yeah.

I was out in California visiting family,
sipping wine in Napa.

I don't know.

My father-in-law would tell you that
maybe the wine is better in Carmel.

So that's where we were hanging out.

OK.

Good.

Welcome back.

Good to have you.

Although you were kind of working
remotely.

I'm still working.

Marty,
you don't really give us a break around

here.

That's true.

But if you come work here,
you will get your allocated days off.

Yeah, yeah.

Great.

Good to see you guys to see you.

Thanks.