Announcer:
0:00
Welcome to MedEvidence, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts Hosted by cardiologist and top medical researcher, Dr Michael Koren.
Dr. Michael Koren:
0:11
Hello, I'm Dr. Michael Koren, the executive editor for MedEvidence, and I'm really excited about the discussion we're about to have, because when I talk with a fellow clinical investigator, there's nothing better than that and I'm fortunate to have Todd Bertoch here, who was a principal investigator and actually the lead investigator for a new pain medicine that just got FDA approval, and we're going to talk about this and some of the challenges of developing pain medications and also some of the excitement about this particular approval. So, todd, welcome to MidEvidence, thank you, thank you so much for having me. It's our pleasure. So, todd, start us off by just telling us a little bit about yourself, a little bit about your background and how you got involved in this program to develop a new pain medicine.
Dr. Todd Bertoch:
0:56
Yeah, I'm an anesthesiologist by training. I practiced for more than 20 years and the last half of my career in clinical practice was focused on pain management and addiction medicine. So I was very interested in the opioid crisis and about eight years ago I came over to the clinical research side and have been pretty much doing that full-time ever since, with a little bit of practice in between, but really excited been the principal investigator for well over 150 clinical trials now in these past eight years and the majority of those have been in pain, and super excited about more recent events, as you described, with some things happening now that are new and exciting.
Dr. Michael Koren:
1:48
Right. So just to give the audience a background, there has been a sea change regarding how we think about pain and how we use pharmaceuticals to treat it. So 20, 30 years ago, we were talking about pain as the fifth vital sign and that no one should leave an emergency room in pain, and that became a problem because, perhaps, of the overuse of narcotics. So why don't you walk us through that a little bit?
Dr. Todd Bertoch:
2:14
Yeah, when I was trained in anesthesia and chronic pain, the dogma at that time was that opioids were great, right, and that if you you know as long as you were helping someone live their normal lifestyle and be able to do their you know tasks of daily living, then you could prescribe as much opioid as you want. They were just great, and it's hard to even say it now. I remember when I trained in the military and when I was first out my very first assignment, I had a pain clinic and I was treating people the way I was trained to treat people with a Marine colonel.
Dr. Todd Bertoch:
3:04
It's tough to become a Marine colonel. You have to be a pretty hard guy to become a Marine colonel, right, I can imagine. Came into my office and just he was. He had tears in his eyes. He basically said you made my wife an addict and that changed everything. At that point, everything changed. I thought, okay, this is not what've been taught is not the right way to go, and from that point on I've just kind of really been interested in this opioid crisis.
Dr. Michael Koren:
3:32
Well, that's intense and for practicing physicians it's actually been difficult to even prescribe opioids. I'm a cardiologist and I don't have that much of a reason to prescribe opioids but I have to refer my patients who might need short-term courses of pain medicine to somebody else because of all the restrictions on sort of an average physician prescribing these drugs.
Dr. Todd Bertoch:
3:58
Yeah, it's tough for the patients and it's tough for the physicians because we just don't have an answer right. If you have someone who has severe pain, the non-opioid choices that we have, you know, don't cover that pain in many instances. But there's social pressures, there's political pressures for physicians not to be able to prescribe opioids, then that has kind of dried up for some of these patients and so we have physicians who can't prescribe the opioids, patients who can't then get the opioids. You've got this big gap where patients who actually need something stronger than the non-opioid choices we have and they're not getting them and we're kind of stuck in the middle as physicians, not knowing kind of where to go.
Dr. Michael Koren:
4:51
Right, yeah, it's been a big problem. So with that, we can transition to this new product called Suzetrigine, if I'm pronouncing that correctly, or Journavx, and you've been very involved in the development of that program. I've been involved in a much smaller way I was a sub-investigator here in Northeast Florida but you're the guy that published the data. So why don't you tell us a little bit about how you got involved in this and why you're excited about this new product?
Dr. Todd Bertoch:
5:18
First of all, while I'm titled the lead investigator, I was tiny cog in the big wheel with the you know pharmaceutical company Vertex that did all of the work behind this. But I was privileged to be able to be part of it all and it's been a, you know, six or eight year journey. It's very difficult, as you know, to get a new drug approved by the FDA and, I think, even more difficult in the pain side for a lot of reasons that we might discuss down the road. But it's been really exciting to have something, just a new alternative, and I think the most exciting part of this is that all the evidence that we've seen so far is not only that it's effective but that it's very safe.
Dr. Michael Koren:
6:09
Yeah, Now do you want to speak to the mechanism of action of Suzetrigine or talk a little bit about the trial designs?
Dr. Todd Bertoch:
6:19
Yeah, well, let's talk about mechanisms of action. This is called a sodium channel inhibitor and, broadly speaking, there are lots of sodium channel inhibitors out there Local anesthetics, for example, like lidocaine, that's a sodium channel inhibitor, but that's a very non-selective sodium channel inhibitor. They're about, depending on who you talk to, somewhere between eight and 10 sodium channel inhibitors on nerve cells in the body and basically these are just little channels that when the nerve is excited it transmits or propagates that kind of nerve impulse to the brain and says I'm having pain down here in my arm or I'm having pain, and blocking those channels basically blocks that impulse from the point of injury to the brain so that people don't sense that pain. That's why if I give someone a sodium or give someone a local anesthetic like lidocaine around their nerve, I completely block transmission of that nerves, that pain signal, through that nerve to the brain and they can feel no pain. You can be operating, you know, with a scalpel and a saw and they don't feel anything. Their brain doesn't feel that pain.
Dr. Todd Bertoch:
7:34
So, um you one might say, well, why not just give everybody oral lidocaine and block all their sodium channel blockers? And, as you know, as cardiologists, there are a lot of sodium channels in the heart and in the brain, and that becomes a lethal proposition. And so what Vertex has done with this molecule is they've isolated one of those sodium channels which is felt to be most associated with pain transmission, and devised a molecule that will block that channel and that channel alone. And so it's a very specific sodium channel inhibitor, and it's called a NAB 1.8 inhibitor because it blocks the sodium channel that they have numbered 1.8.
Dr. Michael Koren:
8:27
Interesting. Yeah, yeah, and that's fascinating. We'll get to safety profile in a second, but you make a really important point, which is that there are different sodium channels in our cells, in our tissues, and it's very important that you have a drug that is specific to the sodium channel 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 channels can cause arrhythmias, and we have drugs that we use for arrhythmias specifically that target sodium channels. So we'll get to that in a second, but that's a fabulous explanation, so thank you for that.
Dr. Michael Koren:
9:04
Before I get to safety, one of the things that I found really interesting was that this drug was approved with a relatively small number of patients by current standards, and maybe that's just related to some of the cardiology studies that I've done, but typically we do studies that involve thousands of people and ultimately, the approvals for things like rosuvastatin, the statin drug, occurred based on 10,000 patients or more, and this was approved based on about 900 patients, as I understand. It's not a trivial number, but smaller than others. So walk us through that a little bit.
Dr. Todd Bertoch:
9:41
Yeah, actually the numbers are a little higher than that. I can explain how that works. Drugs are approved through the FDA in different phases. So we have phase one those are called early phase studies where we're looking mostly at safety of the drug and we're giving this drug to healthy volunteers and just assessing the blood levels of the drugs and any side effects or impacts on other laboratory values or cardiac indications, things like that. And so the drug went through all of those phase one clinical trials, went through pretty extensive phase two clinical trials and then these last phase three trials that actually led to FDA approval were about a thousand patients in each of the two studies. So it ended up being 2,000 patients and, as you mentioned, that's relatively small in the grand scheme of things.
Dr. Todd Bertoch:
10:37
But for pain studies those are actually very large studies. Those are the largest phase three pain studies that I'm aware of that have led to registration for a drug. So they were in. You know, when it comes to pain research they were actually quite large studies, and the reason for that is it's difficult to find people in acute pain. When they're in acute pain, have them sign up for a clinical trial and test the drug in a way that can be very standardized and you can get good data right. So the way we do clinical trials for acute pain is we treat people after they've had certain types of surgery, and those types of surgery are very limited. The FDA only accepts data from a handful of surgery types. Those include people who've had wisdom tooth extractions, bunion surgery, tummy tuck actually abdominoplasty surgery opening renal hernia surgery and total joint replacement.
Dr. Todd Bertoch:
11:48
So really if you're a drug company and you're developing a new pain medicine, you have to do clinical trials in one of these surgical types, and the reason for that is these can be really standardized. So you can organize and create these clinical trials so that patients all kind of have the same pain experience. If you're studying people who have just sprained their ankle, you know some of them have a really bad sprain, some of them don't, some of them have more pain, some of them less. So standardizing these clinical trials is really important. You can decide exactly how much anesthesia they get, what type of anesthesia they get, so they all come out and have kind of the same pain experience and you can test a drug very effectively using these postoperative pain trials.
Dr. Todd Bertoch:
12:58
And then FDA and most of the industry kind of accepts that these results are kind of indicative of what
Dr. Michael Koren:
13:02
So in fact the whole program was closer to 2,000 patients, which is much more reassuring. So in that larger group of 2,000 patients did we see any heart complications or any side effects of the drug that we should take pause as clinicians?
Dr. Todd Bertoch:
13:16
No, honestly this is the first time again. I've been a principal investigator for a lot of pain trials and this is the first time I've ever seen the study drug have fewer side effects we call them adverse events in clinical research, but fewer side effects than the placebo. So more side effects in the placebo arm than in the Suzetrigine arm know a relatively high patient population. I thought that was quite remarkable.
Dr. Michael Koren:
13:47
That's really fabulous. And certainly no cardiac arrhythmia 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 1.8 receptors in the brain. So while the blood does kind of reach the brain, there are no receptors for.8 receptors in the brain. So while the blood does kind of reach the brain, um, there are no receptors for it to act in the brain. And so there were no neurologic complications either.
Dr. Michael Koren:
14:11
That's great. So it won't affect cognition like narcotics, for example.
Dr. Todd Bertoch:
14:15
Yeah, there was no evidence of, yeah, any mental status changes of any kind. There's there's no reason to believe that there would lead to addiction in any way. Again for the same reason that there 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 this medication.
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 thing that we have to consider.
Dr. Todd Bertoch:
15:05
And so people that have mild pain that's on the, you know, mild to moderate scale that respond to acetaminophen or an NSAID. I think most physicians would start with that and either start with one or both. If I need to use both acetaminophen and an NSAID to treat someone's pain, then I'm happy to do that, because they have different mechanisms of action and different toxicities. Where I'm stuck as a prescriber is folks that don't respond to those two, you know, one or both of those medications, and right now my only choice or prior to this drug approval, my choice was to move to an opioid to treat that pain. So now I've got a tool that I can add to my armamentarium that can delay my need to move to an opioid, and I think that's what's most exciting about this drug.
Dr. Michael Koren:
16:12
Is this something that'll be used post-surgery or is it something that will be used after an injury? Just give people a little bit of a sense for the triggering events, as to why you might want to use this particular product.
Dr. Todd Bertoch:
16:25
Yeah, the approval from the FDA. The indication that was approved was for a general acute pain indication, so that includes acute pain from injury or surgery or trauma, whatever is causing that acute pain
Dr. Michael Koren:
16:40
and talk to us a little bit more about what the next steps are for research.
Dr. Michael Koren:
16:44
As clinical researchers, we know that after approval, there are either programs that are mandated by the FDA, for example safety protocols, or there are ways of expanding the use of the product. So maybe you can give us a little insight into what to look for in terms of clinical research moving forward.
Dr. Todd Bertoch:
17:02
Again, I'm not an employee of Vertex so I can't speak for them, but I'm quite certain that they already have publicized clinical research that's ongoing for chronic pain such as neuropathic pain, chronic neuropathic pain like peripheral neuropathy, radicular low back pain. So I think, while the drug's not been approved for this, I think the goal is to see how well this drug works, not only in acute pain but in some of these chronic pain indications, because really that's a much bigger need, right the chronic pain side. And so I think we're all excited to see what those clinical trials look like.
Dr. Michael Koren:
17:47
Absolutely. Is there any studies anticipated 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 evidence that I've seen, I don't think that this is a drug that basically gets me away from having to use morphine or something Dilaudid or something like that. Certain circumstances I have had kidney stones in the past. and you could give me as much ibuprofen and acetaminophen and suzetrogene as you want, but what I had to have dilaudid to get that pain under control right. So I think you know, basically, this is another notch in the belt. You know, another tool that we have to be able to address this pain and I think, the goal. You know what, Mike, I think as a researcher and as a physician.
Dr. Todd Bertoch:
18:45
I kind of came into this with the wrong approach and the wrong expectations and I was thinking, okay, we're all smart, right, we're going to develop a drug that replaces the opioids, and for about two decades that wasn't happening and people were getting kind of discouraged. And I think we need to just change that approach a little bit and change our expectations and say, ok, maybe we're not going to be able to replace opioids, especially in those people that have severe pain, But if we just keep adding to our toolbox things that we can like Suzetrigine for example, because now I can, because Suzetrigine appears to be so safe and because the metabolism is and toxicity is so different than acetaminophen and ibuprofen, now we can add this right, so we don't have to choose. It's not like if I'm treating someone with acetaminophen and ibuprofen and I want to add another NSAID, I can't do that because the toxicities overlap. Well, for this drug the toxicities 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 that we can add to this armamentarium and combine with other pain medicines, then we can approach the efficacy of some of these stronger opioids. And the more we do this, the more we put those opioids kind of off to the side and they're only there for certain circumstances.
Dr. Michael Koren:
20:15
Well, Todd, that was absolutely fabulous explanation. Thank you for educating me. I truly appreciate it and hopefully our audience will appreciate it as well. It really looks like it's a new chapter in pain management. We finally have a new class of drugs first time in two decades and I think we're all excited to see how it fits in the marketplace and, ultimately, what further research is done with this particular product. Any closing words for our audience 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 feels desperate because of the difficulties that we have now with opioids. I think you should take heart. I think there's hope down the line, and that's what we do every day is try to bring hope to people who are struggling with pain, and I think there's a light at the end of the tunnel here.
Dr. Michael Koren:
21:12
Well, todd, thank you very much for being a guest on MedEvidence and, if it's okay with you, we'll post some information about how to get in contact with you, how to get involved in your clinical research, and hopefully that will be helpful to you moving forward 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 to MedEvidence. com or subscribe to our podcast on your favorite podcast platform.
