February 26, 2025 • 21 mins
Anesthesiologist Dr. Todd Bertoch speaks with Dr. Michael Koren in this exciting episode about the a new pain medication, Journavx (suzetrigine), which was just approved by the FDA in January, 2025. The doctors discuss this breakthrough pain management medication, its safety profile, side effects, and how it compares to NSAIDs, acetaminophen, and opioids. They also dive into the approval process, how trials were conducted and standardized, and where the medication will go from here.
Koren's Key Takeaways:
- New options like suzetrigine for pain medication that are non-addicting are needed
- This medication is another tool, not a replacement for opioids
- The clinical trials for this medication have been rigorous
Be a part of advancing science by participating in clinical research.
Have a question for Dr. Koren? Email him at askDrKoren@MedEvidence.com
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Announcer (00:00):
Welcome to MedEvidence, where we help you
navigate the truth behindmedical research with unbiased,
evidence-proven facts Hosted bycardiologist and top medical
researcher, Dr Michael Koren.
Dr. Michael Koren (00:11):
Hello, I'm Dr .
Michael Koren, the executiveeditor for MedEvidence, and I'm
really excited about thediscussion we're about to have,
because when I talk with afellow clinical investigator,
there's nothing better than thatand I'm fortunate to have Todd
Bertoch here, who was aprincipal investigator and
actually the lead investigatorfor a new pain medicine that
(00:33):
just got FDA approval, and we'regoing to talk about this and
some of the challenges ofdeveloping pain medications and
also some of the excitementabout this particular approval.
So, todd, welcome toMidEvidence, thank you, thank
you so much for having me.
It's our pleasure.
So, todd, start us off by justtelling us a little bit about
yourself, a little bit aboutyour background and how you got
(00:53):
involved in this program todevelop a new pain medicine.
Dr. Todd Bertoch (00:56):
Yeah, I'm an anesthesiologist by training.
I practiced for more than 20years and the last half of my
career in clinical practice wasfocused on pain management and
addiction medicine.
So I was very interested in theopioid crisis and about eight
years ago I came over to theclinical research side and have
(01:21):
been pretty much doing thatfull-time ever since, with a
little bit of practice inbetween, but really excited been
the principal investigator forwell over 150 clinical trials
now in these past eight yearsand the majority of those have
been in pain, and super excitedabout more recent events, as you
(01:42):
described, with some thingshappening now that are new and
exciting.
Dr. Michael Koren (01:48):
Right.
So just to give the audience abackground, there has been a sea
change regarding how we thinkabout pain and how we use
pharmaceuticals to treat it.
So 20, 30 years ago, we weretalking about pain as the fifth
vital sign and that no oneshould leave an emergency room
in pain, and that became aproblem because, perhaps, of the
(02:10):
overuse of narcotics.
So why don't you walk usthrough that a little bit?
Dr. Todd Bertoch (02:14):
Yeah, when I was trained in anesthesia and
chronic pain, the dogma at thattime was that opioids were great
, right, and that if you youknow as long as you were helping
someone live their normallifestyle and be able to do
their you know tasks of dailyliving, then you could prescribe
(02:38):
as much opioid as you want.
They were just great, and it'shard to even say it now.
I remember when I trained inthe military and when I was
(03:01):
first out my very firstassignment, I had a pain clinic
and I was treating people theway I was trained to treat
people with a Marine colonel.
It's tough to become a Marinecolonel.
You have to be a pretty hardguy to become a Marine colonel,
right, I can imagine.
Came into my office and just hewas.
He had tears in his eyes.
He basically said you made mywife an addict and that changed
(03:21):
everything.
At that point, everythingchanged.
I thought, okay, this is notwhat've been taught is not the
right way to go, and from thatpoint on I've just kind of
really been interested in thisopioid crisis.
Dr. Michael Koren (03:32):
Well, that's intense and for practicing
physicians it's actually beendifficult to even prescribe
opioids.
I'm a cardiologist and I don'thave that much of a reason to
prescribe opioids but I have torefer my patients who might need
short-term courses of painmedicine to somebody else
(03:52):
because of all the restrictionson sort of an average physician
prescribing these drugs.
Dr. Todd Bertoch (03:58):
Yeah, it's tough for the patients and it's
tough for the physicians becausewe just don't have an answer
right.
If you have someone who hassevere pain, the non-opioid
choices that we have, you know,don't cover that pain in many
instances.
(04:18):
But there's social pressures,there's political pressures for
physicians not to be able toprescribe opioids, then that has
kind of dried up for some ofthese patients and so we have
physicians who can't prescribethe opioids, patients who can't
then get the opioids.
You've got this big gap wherepatients who actually need
(04:41):
something stronger than thenon-opioid choices we have and
they're not getting them andwe're kind of stuck in the
middle as physicians, notknowing kind of where to go.
Dr. Michael Koren (04:51):
Right, yeah, it's been a big problem.
So with that, we can transitionto this new product called
Suzetrigine, if I'm pronouncingthat correctly, or Journavx, and
you've been very involved inthe development of that program.
I've been involved in a muchsmaller way I was a
sub-investigator here inNortheast Florida but you're the
guy that published the data.
(05:11):
So why don't you tell us alittle bit about how you got
involved in this and why you'reexcited about this new product?
Dr. Todd Bertoch (05:18):
First of all, while I'm titled the lead
investigator, I was tiny cog inthe big wheel with the you know
pharmaceutical company Vertexthat did all of the work behind
this.
But I was privileged to be ableto be part of it all and it's
been a, you know, six or eightyear journey.
(05:39):
It's very difficult, as youknow, to get a new drug approved
by the FDA and, I think, evenmore difficult in the pain side
for a lot of reasons that wemight discuss down the road.
But it's been really excitingto have something, just a new
(05:59):
alternative, and I think themost exciting part of this is
that all the evidence that we'veseen so far is not only that
it's effective but that it'svery safe.
Dr. Michael Koren (06:09):
Yeah, Now do you want to speak to the
mechanism of action ofSuzetrigine or talk a little bit
about the trial designs?
Dr. Todd Bertoch (06:19):
Yeah, well, let's talk about mechanisms of
action.
This is called a sodium channelinhibitor and, broadly speaking
, there are lots of sodiumchannel inhibitors out there
Local anesthetics, for example,like lidocaine, that's a sodium
channel inhibitor, but that's avery non-selective sodium
channel inhibitor.
They're about, depending on whoyou talk to, somewhere between
(06:41):
eight and 10 sodium channelinhibitors on nerve cells in the
body and basically these arejust little channels that when
the nerve is excited ittransmits or propagates that
kind of nerve impulse to thebrain and says I'm having pain
down here in my arm or I'mhaving pain, and blocking those
(07:04):
channels basically blocks thatimpulse from the point of injury
to the brain so that peopledon't sense that pain.
That's why if I give someone asodium or give someone a local
anesthetic like lidocaine aroundtheir nerve, I completely block
transmission of that nerves,that pain signal, through that
nerve to the brain and they canfeel no pain.
(07:26):
You can be operating, you know,with a scalpel and a saw and
they don't feel anything.
Their brain doesn't feel thatpain.
So, um you one might say, well,why not just give everybody oral
lidocaine and block all theirsodium channel blockers?
And, as you know, ascardiologists, there are a lot
of sodium channels in the heartand in the brain, and that
(07:48):
becomes a lethal proposition.
And so what Vertex has donewith this molecule is they've
isolated one of those sodiumchannels which is felt to be
most associated with paintransmission, and devised a
(08:08):
molecule that will block thatchannel and that channel alone.
And so it's a very specificsodium channel inhibitor, and
it's called a NAB 1.8 inhibitorbecause it blocks the sodium
channel that they have numbered1.8.
Dr. Michael Koren (08:27):
Interesting.
Yeah, yeah, and that'sfascinating.
We'll get to safety profile ina second, but you make a really
important point, which is thatthere are different sodium
channels in our cells, in ourtissues, and it's very important
that you have a drug that isspecific to the sodium channel
(08:47):
that you want to target, because, as you mentioned, there are
sodium channels in the heart and, in fact, we know that
affecting those sodium channelscan cause arrhythmias, and we
have drugs that we use forarrhythmias specifically that
target sodium channels.
So we'll get to that in asecond, but that's a fabulous
explanation, so thank you forthat.
Before I get to safety, one ofthe things that I found really
interesting was that this drugwas approved with a relatively
(09:11):
small number of patients bycurrent standards, and maybe
that's just related to some ofthe cardiology studies that I've
done, but typically we dostudies that involve thousands
of people and ultimately, theapprovals for things like
rosuvastatin, the statin drug,occurred based on 10,000
(09:31):
patients or more, and this wasapproved based on about 900
patients, as I understand.
It's not a trivial number, butsmaller than others.
So walk us through that alittle bit.
Dr. Todd Bertoch (09:41):
Yeah, actually the numbers are a little higher
than that.
I can explain how that works.
Drugs are approved through theFDA in different phases.
So we have phase one those arecalled early phase studies where
we're looking mostly at safetyof the drug and we're giving
this drug to healthy volunteersand just assessing the blood
(10:02):
levels of the drugs and any sideeffects or impacts on other
laboratory values or cardiacindications, things like that.
And so the drug went throughall of those phase one clinical
trials, went through prettyextensive phase two clinical
trials and then these last phasethree trials that actually led
(10:24):
to FDA approval were about athousand patients in each of the
two studies.
So it ended up being 2,000patients and, as you mentioned,
that's relatively small in thegrand scheme of things.
But for pain studies those areactually very large studies.
Those are the largest phasethree pain studies that I'm
(10:46):
aware of that have led toregistration for a drug.
So they were in.
You know, when it comes to painresearch they were actually
quite large studies, and thereason for that is it's
difficult to find people inacute pain.
When they're in acute pain,have them sign up for a clinical
(11:07):
trial and test the drug in away that can be very
standardized and you can getgood data right.
So the way we do clinicaltrials for acute pain is we
treat people after they've hadcertain types of surgery, and
those types of surgery are verylimited.
The FDA only accepts data froma handful of surgery types.
(11:31):
Those include people who've hadwisdom tooth extractions,
bunion surgery, tummy tuckactually abdominoplasty surgery
opening renal hernia surgery andtotal joint replacement.
So really if you're a drugcompany and you're developing a
new pain medicine, you have todo clinical trials in one of
(11:55):
these surgical types, and thereason for that is these can be
really standardized.
So you can organize and createthese clinical trials so that
patients all kind of have thesame pain experience.
If you're studying people whohave just sprained their ankle,
(12:16):
you know some of them have areally bad sprain, some of them
don't, some of them have morepain, some of them less.
So standardizing these clinicaltrials is really important.
You can decide exactly how muchanesthesia they get, what type
of anesthesia they get, so theyall come out and have kind of
the same pain experience and youcan test a drug very
effectively using thesepostoperative pain trials.
(12:58):
And then FDA and most of theindustry kind of accepts that
these results are kind ofindicative of what
So in fact the whole programwas closer to 2,000 patients,
which is much more reassuring.
So in that larger group of2,000 patients did we see any
heart complications or any sideeffects of the drug that we
should take pause as clinicians?
No, honestly this is the first time again.
(13:18):
I've been a principalinvestigator for a lot of pain
trials and this is the firsttime I've ever seen the study
drug have fewer side effects wecall them adverse events in
clinical research, but fewerside effects than the placebo.
So more side effects in theplacebo arm than in the
(13:41):
Suzetrigine arm know arelatively high patient
population.
I thought that was quiteremarkable.
Dr. Michael Koren (13:47):
That's really fabulous.
And certainly no cardiacarrhythmia issues that we talked
about before as a concern.
Dr. Todd Bertoch (13:53):
Yeah, none at all.
Dr. Michael Koren (13:54):
That's beautiful
Dr. Todd Bertoch (13:55):
The drug crosses the blood-brain barrier,
but there are not NAV 1.8receptors in the brain.
So while the blood does kind ofreach the brain, there are no
receptors for.8 receptors in thebrain.
So while the blood does kind ofreach the brain, um, there are
no receptors for it to act inthe brain.
And so there were no neurologiccomplications either.
Dr. Michael Koren (14:11):
That's great.
So it won't affect cognitionlike narcotics, for example.
Dr. Todd Bertoch (14:15):
Yeah, there was no evidence of, yeah, any
mental status changes of anykind.
There's there's no reason tobelieve that there would lead to
addiction in any way.
Again for the same reason thatthere aren't any receptors in
the brain.
Dr. Michael Koren (14:30):
So people shouldn't be fearful of driving
a car when they're taking thismedication.
Dr. Todd Bertoch (14:36):
Based on the evidence that we have absolutely
not.
Dr. Michael Koren (14:38):
Beautiful.
That's actually really exciting.
That's tremendous stuff.
So I have two, really one thingthat we have to consider.
Dr. Todd Bertoch (15:05):
And so people that have mild pain that's on
the, you know, mild to moderatescale that respond to
acetaminophen or an NSAID.
I think most physicians wouldstart with that and either start
with one or both.
If I need to use bothacetaminophen and an NSAID to
(15:28):
treat someone's pain, then I'mhappy to do that, because they
have different mechanisms ofaction and different toxicities.
Where I'm stuck as a prescriberis folks that don't respond to
those two, you know, one or bothof those medications, and right
now my only choice or prior tothis drug approval, my choice
(15:50):
was to move to an opioid totreat that pain.
So now I've got a tool that Ican add to my armamentarium that
can delay my need to move to anopioid, and I think that's
what's most exciting about thisdrug.
Dr. Michael Koren (16:12):
Is this something that'll be used
post-surgery or is it somethingthat will be used after an
injury?
Just give people a little bitof a sense for the triggering
events, as to why you might wantto use this particular product.
Dr. Todd Bertoch (16:25):
Yeah, the approval from the FDA.
The indication that wasapproved was for a general acute
pain indication, so thatincludes acute pain from injury
or surgery or trauma, whateveris causing that acute pain
and talk to us a little bitmore about what the next steps
are for research.
As clinical researchers, we knowthat after approval, there are
(16:48):
either programs that aremandated by the FDA, for example
safety protocols, or there areways of expanding the use of the
product.
So maybe you can give us alittle insight into what to look
for in terms of clinicalresearch moving forward.
Again, I'm not an employee of Vertex so I
can't speak for them, but I'mquite certain that they already
(17:11):
have publicized clinicalresearch that's ongoing for
chronic pain such as neuropathicpain, chronic neuropathic pain
like peripheral neuropathy,radicular low back pain.
So I think, while the drug'snot been approved for this, I
think the goal is to see howwell this drug works, not only
(17:32):
in acute pain but in some ofthese chronic pain indications,
because really that's a muchbigger need, right the chronic
pain side.
And so I think we're allexcited to see what those
clinical trials look like.
Dr. Michael Koren (17:47):
Absolutely.
Is there any studiesanticipated to use Suzetrigine
to replace narcotics?
Dr. Todd Bertoch (17:55):
That's a great question and right now I don't
think, based on the evidencethat I've seen, I don't think
that this is a drug thatbasically gets me away from
having to use morphine orsomething Dilaudid or something
like that.
Certain circumstances I havehad kidney stones in the past.
and you could give me as muchibuprofen and acetaminophen and
(18:22):
suzetrogene as you want, butwhat I had to have dilaudid to
get that pain under controlright.
So I think you know, basically,this is another notch in the
belt.
You know, another tool that wehave to be able to address this
pain and I think, the goal.
You know what, Mike, I think asa researcher and as a physician
(18:44):
.
I kind of came into this withthe wrong approach and the wrong
expectations and I was thinking, okay, we're all smart, right,
we're going to develop a drugthat replaces the opioids, and
for about two decades thatwasn't happening and people were
getting kind of discouraged.
And I think we need to justchange that approach a little
(19:09):
bit and change our expectationsand say, ok, maybe we're not
going to be able to replaceopioids, especially in those
people that have severe pain,But if we just keep adding to
our toolbox things that we canlike Suzetrigine for example,
because now I can, becauseSuzetrigine appears to be so
safe and because the metabolismis and toxicity is so different
(19:31):
than acetaminophen and ibuprofen, now we can add this right, so
we don't have to choose.
It's not like if I'm treatingsomeone with acetaminophen and
ibuprofen and I want to addanother NSAID, I can't do that
because the toxicities overlap.
Well, for this drug thetoxicities don't overlap, so we
can add them right.
Dr. Michael Koren (19:51):
That's a great point
Dr. Todd Bertoch (19:53):
and that's really I think, as we continue
to develop new medications thatwe can add to this armamentarium
and combine with other painmedicines, then we can approach
the efficacy of some of thesestronger opioids.
And the more we do this, themore we put those opioids kind
of off to the side and they'reonly there for certain
(20:14):
circumstances.
Dr. Michael Koren (20:15):
Well, Todd, that was absolutely fabulous
explanation.
Thank you for educating me.
I truly appreciate it andhopefully our audience will
appreciate it as well.
It really looks like it's a newchapter in pain management.
We finally have a new class ofdrugs first time in two decades
and I think we're all excited tosee how it fits in the
marketplace and, ultimately,what further research is done
(20:37):
with this particular product.
Any closing words for ouraudience Suzetrigine or or pain
management in general.
Dr. Todd Bertoch (20:52):
No, I think there's a lot of energy on.
Or a patient who feelsdesperate because of the
difficulties that we have nowwith opioids.
I think you should take heart.
I think there's hope down theline, and that's what we do
every day is try to bring hopeto people who are struggling
with pain, and I think there's alight at the end of the tunnel
(21:12):
here.
Dr. Michael Koren (21:12):
Well, todd, thank you very much for being a
guest on MedEvidence and, ifit's okay with you, we'll post
some information about how toget in contact with you, how to
get involved in your clinicalresearch, and hopefully that
will be helpful to you movingforward in terms of further
research in these areas.
Dr. Todd Bertoch (21:29):
That would be great, thanks, thanks so much
for having me.
Announcer (21:31):
Thanks for joining the MedEvidence podcast.
To learn more, head over toMedEvidence.
com or subscribe to our podcaston your favorite podcast
platform.
Welcome to MedEvidence, where we help you
navigate the truth behindmedical research with unbiased,
evidence-proven facts Hosted bycardiologist and top medical
researcher, Dr Michael Koren.
Dr. Michael Koren (00:11):
Hello, I'm Dr .
Michael Koren, the executiveeditor for MedEvidence, and I'm
really excited about thediscussion we're about to have,
because when I talk with afellow clinical investigator,
there's nothing better than thatand I'm fortunate to have Todd
Bertoch here, who was aprincipal investigator and
actually the lead investigatorfor a new pain medicine that
(00:33):
just got FDA approval, and we'regoing to talk about this and
some of the challenges ofdeveloping pain medications and
also some of the excitementabout this particular approval.
So, todd, welcome toMidEvidence, thank you, thank
you so much for having me.
It's our pleasure.
So, todd, start us off by justtelling us a little bit about
yourself, a little bit aboutyour background and how you got
(00:53):
involved in this program todevelop a new pain medicine.
Dr. Todd Bertoch (00:56):
Yeah, I'm an anesthesiologist by training.
I practiced for more than 20years and the last half of my
career in clinical practice wasfocused on pain management and
addiction medicine.
So I was very interested in theopioid crisis and about eight
years ago I came over to theclinical research side and have
(01:21):
been pretty much doing thatfull-time ever since, with a
little bit of practice inbetween, but really excited been
the principal investigator forwell over 150 clinical trials
now in these past eight yearsand the majority of those have
been in pain, and super excitedabout more recent events, as you
(01:42):
described, with some thingshappening now that are new and
exciting.
Dr. Michael Koren (01:48):
Right.
So just to give the audience abackground, there has been a sea
change regarding how we thinkabout pain and how we use
pharmaceuticals to treat it.
So 20, 30 years ago, we weretalking about pain as the fifth
vital sign and that no oneshould leave an emergency room
in pain, and that became aproblem because, perhaps, of the
(02:10):
overuse of narcotics.
So why don't you walk usthrough that a little bit?
Dr. Todd Bertoch (02:14):
Yeah, when I was trained in anesthesia and
chronic pain, the dogma at thattime was that opioids were great
, right, and that if you youknow as long as you were helping
someone live their normallifestyle and be able to do
their you know tasks of dailyliving, then you could prescribe
(02:38):
as much opioid as you want.
They were just great, and it'shard to even say it now.
I remember when I trained inthe military and when I was
(03:01):
first out my very firstassignment, I had a pain clinic
and I was treating people theway I was trained to treat
people with a Marine colonel.
It's tough to become a Marinecolonel.
You have to be a pretty hardguy to become a Marine colonel,
right, I can imagine.
Came into my office and just hewas.
He had tears in his eyes.
He basically said you made mywife an addict and that changed
(03:21):
everything.
At that point, everythingchanged.
I thought, okay, this is notwhat've been taught is not the
right way to go, and from thatpoint on I've just kind of
really been interested in thisopioid crisis.
Dr. Michael Koren (03:32):
Well, that's intense and for practicing
physicians it's actually beendifficult to even prescribe
opioids.
I'm a cardiologist and I don'thave that much of a reason to
prescribe opioids but I have torefer my patients who might need
short-term courses of painmedicine to somebody else
(03:52):
because of all the restrictionson sort of an average physician
prescribing these drugs.
Dr. Todd Bertoch (03:58):
Yeah, it's tough for the patients and it's
tough for the physicians becausewe just don't have an answer
right.
If you have someone who hassevere pain, the non-opioid
choices that we have, you know,don't cover that pain in many
instances.
(04:18):
But there's social pressures,there's political pressures for
physicians not to be able toprescribe opioids, then that has
kind of dried up for some ofthese patients and so we have
physicians who can't prescribethe opioids, patients who can't
then get the opioids.
You've got this big gap wherepatients who actually need
(04:41):
something stronger than thenon-opioid choices we have and
they're not getting them andwe're kind of stuck in the
middle as physicians, notknowing kind of where to go.
Dr. Michael Koren (04:51):
Right, yeah, it's been a big problem.
So with that, we can transitionto this new product called
Suzetrigine, if I'm pronouncingthat correctly, or Journavx, and
you've been very involved inthe development of that program.
I've been involved in a muchsmaller way I was a
sub-investigator here inNortheast Florida but you're the
guy that published the data.
(05:11):
So why don't you tell us alittle bit about how you got
involved in this and why you'reexcited about this new product?
Dr. Todd Bertoch (05:18):
First of all, while I'm titled the lead
investigator, I was tiny cog inthe big wheel with the you know
pharmaceutical company Vertexthat did all of the work behind
this.
But I was privileged to be ableto be part of it all and it's
been a, you know, six or eightyear journey.
(05:39):
It's very difficult, as youknow, to get a new drug approved
by the FDA and, I think, evenmore difficult in the pain side
for a lot of reasons that wemight discuss down the road.
But it's been really excitingto have something, just a new
(05:59):
alternative, and I think themost exciting part of this is
that all the evidence that we'veseen so far is not only that
it's effective but that it'svery safe.
Dr. Michael Koren (06:09):
Yeah, Now do you want to speak to the
mechanism of action ofSuzetrigine or talk a little bit
about the trial designs?
Dr. Todd Bertoch (06:19):
Yeah, well, let's talk about mechanisms of
action.
This is called a sodium channelinhibitor and, broadly speaking
, there are lots of sodiumchannel inhibitors out there
Local anesthetics, for example,like lidocaine, that's a sodium
channel inhibitor, but that's avery non-selective sodium
channel inhibitor.
They're about, depending on whoyou talk to, somewhere between
(06:41):
eight and 10 sodium channelinhibitors on nerve cells in the
body and basically these arejust little channels that when
the nerve is excited ittransmits or propagates that
kind of nerve impulse to thebrain and says I'm having pain
down here in my arm or I'mhaving pain, and blocking those
(07:04):
channels basically blocks thatimpulse from the point of injury
to the brain so that peopledon't sense that pain.
That's why if I give someone asodium or give someone a local
anesthetic like lidocaine aroundtheir nerve, I completely block
transmission of that nerves,that pain signal, through that
nerve to the brain and they canfeel no pain.
(07:26):
You can be operating, you know,with a scalpel and a saw and
they don't feel anything.
Their brain doesn't feel thatpain.
So, um you one might say, well,why not just give everybody oral
lidocaine and block all theirsodium channel blockers?
And, as you know, ascardiologists, there are a lot
of sodium channels in the heartand in the brain, and that
(07:48):
becomes a lethal proposition.
And so what Vertex has donewith this molecule is they've
isolated one of those sodiumchannels which is felt to be
most associated with paintransmission, and devised a
(08:08):
molecule that will block thatchannel and that channel alone.
And so it's a very specificsodium channel inhibitor, and
it's called a NAB 1.8 inhibitorbecause it blocks the sodium
channel that they have numbered1.8.
Dr. Michael Koren (08:27):
Interesting.
Yeah, yeah, and that'sfascinating.
We'll get to safety profile ina second, but you make a really
important point, which is thatthere are different sodium
channels in our cells, in ourtissues, and it's very important
that you have a drug that isspecific to the sodium channel
(08:47):
that you want to target, because, as you mentioned, there are
sodium channels in the heart and, in fact, we know that
affecting those sodium channelscan cause arrhythmias, and we
have drugs that we use forarrhythmias specifically that
target sodium channels.
So we'll get to that in asecond, but that's a fabulous
explanation, so thank you forthat.
Before I get to safety, one ofthe things that I found really
interesting was that this drugwas approved with a relatively
(09:11):
small number of patients bycurrent standards, and maybe
that's just related to some ofthe cardiology studies that I've
done, but typically we dostudies that involve thousands
of people and ultimately, theapprovals for things like
rosuvastatin, the statin drug,occurred based on 10,000
(09:31):
patients or more, and this wasapproved based on about 900
patients, as I understand.
It's not a trivial number, butsmaller than others.
So walk us through that alittle bit.
Dr. Todd Bertoch (09:41):
Yeah, actually the numbers are a little higher
than that.
I can explain how that works.
Drugs are approved through theFDA in different phases.
So we have phase one those arecalled early phase studies where
we're looking mostly at safetyof the drug and we're giving
this drug to healthy volunteersand just assessing the blood
(10:02):
levels of the drugs and any sideeffects or impacts on other
laboratory values or cardiacindications, things like that.
And so the drug went throughall of those phase one clinical
trials, went through prettyextensive phase two clinical
trials and then these last phasethree trials that actually led
(10:24):
to FDA approval were about athousand patients in each of the
two studies.
So it ended up being 2,000patients and, as you mentioned,
that's relatively small in thegrand scheme of things.
But for pain studies those areactually very large studies.
Those are the largest phasethree pain studies that I'm
(10:46):
aware of that have led toregistration for a drug.
So they were in.
You know, when it comes to painresearch they were actually
quite large studies, and thereason for that is it's
difficult to find people inacute pain.
When they're in acute pain,have them sign up for a clinical
(11:07):
trial and test the drug in away that can be very
standardized and you can getgood data right.
So the way we do clinicaltrials for acute pain is we
treat people after they've hadcertain types of surgery, and
those types of surgery are verylimited.
The FDA only accepts data froma handful of surgery types.
(11:31):
Those include people who've hadwisdom tooth extractions,
bunion surgery, tummy tuckactually abdominoplasty surgery
opening renal hernia surgery andtotal joint replacement.
So really if you're a drugcompany and you're developing a
new pain medicine, you have todo clinical trials in one of
(11:55):
these surgical types, and thereason for that is these can be
really standardized.
So you can organize and createthese clinical trials so that
patients all kind of have thesame pain experience.
If you're studying people whohave just sprained their ankle,
(12:16):
you know some of them have areally bad sprain, some of them
don't, some of them have morepain, some of them less.
So standardizing these clinicaltrials is really important.
You can decide exactly how muchanesthesia they get, what type
of anesthesia they get, so theyall come out and have kind of
the same pain experience and youcan test a drug very
effectively using thesepostoperative pain trials.
(12:58):
And then FDA and most of theindustry kind of accepts that
these results are kind ofindicative of what
So in fact the whole programwas closer to 2,000 patients,
which is much more reassuring.
So in that larger group of2,000 patients did we see any
heart complications or any sideeffects of the drug that we
should take pause as clinicians?
No, honestly this is the first time again.
(13:18):
I've been a principalinvestigator for a lot of pain
trials and this is the firsttime I've ever seen the study
drug have fewer side effects wecall them adverse events in
clinical research, but fewerside effects than the placebo.
So more side effects in theplacebo arm than in the
(13:41):
Suzetrigine arm know arelatively high patient
population.
I thought that was quiteremarkable.
Dr. Michael Koren (13:47):
That's really fabulous.
And certainly no cardiacarrhythmia issues that we talked
about before as a concern.
Dr. Todd Bertoch (13:53):
Yeah, none at all.
Dr. Michael Koren (13:54):
That's beautiful
Dr. Todd Bertoch (13:55):
The drug crosses the blood-brain barrier,
but there are not NAV 1.8receptors in the brain.
So while the blood does kind ofreach the brain, there are no
receptors for.8 receptors in thebrain.
So while the blood does kind ofreach the brain, um, there are
no receptors for it to act inthe brain.
And so there were no neurologiccomplications either.
Dr. Michael Koren (14:11):
That's great.
So it won't affect cognitionlike narcotics, for example.
Dr. Todd Bertoch (14:15):
Yeah, there was no evidence of, yeah, any
mental status changes of anykind.
There's there's no reason tobelieve that there would lead to
addiction in any way.
Again for the same reason thatthere aren't any receptors in
the brain.
Dr. Michael Koren (14:30):
So people shouldn't be fearful of driving
a car when they're taking thismedication.
Dr. Todd Bertoch (14:36):
Based on the evidence that we have absolutely
not.
Dr. Michael Koren (14:38):
Beautiful.
That's actually really exciting.
That's tremendous stuff.
So I have two, really one thingthat we have to consider.
Dr. Todd Bertoch (15:05):
And so people that have mild pain that's on
the, you know, mild to moderatescale that respond to
acetaminophen or an NSAID.
I think most physicians wouldstart with that and either start
with one or both.
If I need to use bothacetaminophen and an NSAID to
(15:28):
treat someone's pain, then I'mhappy to do that, because they
have different mechanisms ofaction and different toxicities.
Where I'm stuck as a prescriberis folks that don't respond to
those two, you know, one or bothof those medications, and right
now my only choice or prior tothis drug approval, my choice
(15:50):
was to move to an opioid totreat that pain.
So now I've got a tool that Ican add to my armamentarium that
can delay my need to move to anopioid, and I think that's
what's most exciting about thisdrug.
Dr. Michael Koren (16:12):
Is this something that'll be used
post-surgery or is it somethingthat will be used after an
injury?
Just give people a little bitof a sense for the triggering
events, as to why you might wantto use this particular product.
Dr. Todd Bertoch (16:25):
Yeah, the approval from the FDA.
The indication that wasapproved was for a general acute
pain indication, so thatincludes acute pain from injury
or surgery or trauma, whateveris causing that acute pain
and talk to us a little bitmore about what the next steps
are for research.
As clinical researchers, we knowthat after approval, there are
(16:48):
either programs that aremandated by the FDA, for example
safety protocols, or there areways of expanding the use of the
product.
So maybe you can give us alittle insight into what to look
for in terms of clinicalresearch moving forward.
Again, I'm not an employee of Vertex so I
can't speak for them, but I'mquite certain that they already
(17:11):
have publicized clinicalresearch that's ongoing for
chronic pain such as neuropathicpain, chronic neuropathic pain
like peripheral neuropathy,radicular low back pain.
So I think, while the drug'snot been approved for this, I
think the goal is to see howwell this drug works, not only
(17:32):
in acute pain but in some ofthese chronic pain indications,
because really that's a muchbigger need, right the chronic
pain side.
And so I think we're allexcited to see what those
clinical trials look like.
Dr. Michael Koren (17:47):
Absolutely.
Is there any studiesanticipated to use Suzetrigine
to replace narcotics?
Dr. Todd Bertoch (17:55):
That's a great question and right now I don't
think, based on the evidencethat I've seen, I don't think
that this is a drug thatbasically gets me away from
having to use morphine orsomething Dilaudid or something
like that.
Certain circumstances I havehad kidney stones in the past.
and you could give me as muchibuprofen and acetaminophen and
(18:22):
suzetrogene as you want, butwhat I had to have dilaudid to
get that pain under controlright.
So I think you know, basically,this is another notch in the
belt.
You know, another tool that wehave to be able to address this
pain and I think, the goal.
You know what, Mike, I think asa researcher and as a physician
(18:44):
.
I kind of came into this withthe wrong approach and the wrong
expectations and I was thinking, okay, we're all smart, right,
we're going to develop a drugthat replaces the opioids, and
for about two decades thatwasn't happening and people were
getting kind of discouraged.
And I think we need to justchange that approach a little
(19:09):
bit and change our expectationsand say, ok, maybe we're not
going to be able to replaceopioids, especially in those
people that have severe pain,But if we just keep adding to
our toolbox things that we canlike Suzetrigine for example,
because now I can, becauseSuzetrigine appears to be so
safe and because the metabolismis and toxicity is so different
(19:31):
than acetaminophen and ibuprofen, now we can add this right, so
we don't have to choose.
It's not like if I'm treatingsomeone with acetaminophen and
ibuprofen and I want to addanother NSAID, I can't do that
because the toxicities overlap.
Well, for this drug thetoxicities don't overlap, so we
can add them right.
Dr. Michael Koren (19:51):
That's a great point
Dr. Todd Bertoch (19:53):
and that's really I think, as we continue
to develop new medications thatwe can add to this armamentarium
and combine with other painmedicines, then we can approach
the efficacy of some of thesestronger opioids.
And the more we do this, themore we put those opioids kind
of off to the side and they'reonly there for certain
(20:14):
circumstances.
Dr. Michael Koren (20:15):
Well, Todd, that was absolutely fabulous
explanation.
Thank you for educating me.
I truly appreciate it andhopefully our audience will
appreciate it as well.
It really looks like it's a newchapter in pain management.
We finally have a new class ofdrugs first time in two decades
and I think we're all excited tosee how it fits in the
marketplace and, ultimately,what further research is done
(20:37):
with this particular product.
Any closing words for ouraudience Suzetrigine or or pain
management in general.
Dr. Todd Bertoch (20:52):
No, I think there's a lot of energy on.
Or a patient who feelsdesperate because of the
difficulties that we have nowwith opioids.
I think you should take heart.
I think there's hope down theline, and that's what we do
every day is try to bring hopeto people who are struggling
with pain, and I think there's alight at the end of the tunnel
(21:12):
here.
Dr. Michael Koren (21:12):
Well, todd, thank you very much for being a
guest on MedEvidence and, ifit's okay with you, we'll post
some information about how toget in contact with you, how to
get involved in your clinicalresearch, and hopefully that
will be helpful to you movingforward in terms of further
research in these areas.
Dr. Todd Bertoch (21:29):
That would be great, thanks, thanks so much
for having me.
Announcer (21:31):
Thanks for joining the MedEvidence podcast.
To learn more, head over toMedEvidence.
com or subscribe to our podcaston your favorite podcast
platform.
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