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- [00:01]
A
I'm john strum and this is real talk, mississippi. It's February 3rd and we have a lot to talk about. I'm in San Diego this week for the annual forum hosted by the Americas Committee for Treatment and Research in Multiple Sclerosis, better known as actrims. I'm looking forward to speaking with some of the scientists, clinicians and young investigators who are here to share the latest insights and discoveries about Ms. One of the things I'll be doing this week is hosting the first official Actrooms Forum podcast. It's called the Actrooms Forum Insider and you'll hear new episodes on February 6th, 7th and 8th, recapping the previous day's research presentations and announcements. You'll find the ACT Rooms Forum Insider on Apple Podcasts, Spotify, or wherever you find your favorite podcasts. But today I'm going to take you back a couple of months to this past December when the FDA surprised a lot of people in the Ms. Community by issuing what's called a complete response letter to drug manufacturer Sanofi in response to Sanofi's application seeking approval for tolebrutinib, the first in a new category of investigational disease modifying therapies to go through the FDA's approval process. A complete response letter is an official letter from the FDA to a drug manufacturer stating that the agency can't approve a new medicine in its current form. It's not an outright no that kills a project, it's more like a not yet. However, this complete response letter raised some issues which at first glance don't appear to be easily fixable. For example, the FDA seemed to have issues with the design of a clinical trial that had already taken place over a period of years. Sanofi has pointed out that the issues raised in the complete response letter were markedly different from the guidance they had been given by the FDA over the course of this approval process, and Sanofi has indicated that they would work with the FDA to find a path forward for tolebrutinib. Meanwhile, Dr. William Conti, an Ms. Specialist and principal investigator in the Phase 3 clinical trial for tolebrutinib, has published an article responding to the FDA's complete response letter. Dr. Conti's article resonated with me, so I contacted Dr. Conti and invited him to join me on the podcast to discuss the FDA's action and his response to that action. Dr. Conti immediately agreed to join me and we had a detailed, in depth conversation that you're about to hear. But first, I want to remind you that this episode of Real Talk Ms. Is sponsored by Able now, a Tax Advantage savings program for people with disabilities. If you're living with multiple sclerosis, this is important news. Expanded federal rules mean more adults with disabilities, including many people with ms, can open an Able now accountability. ABLE now lets individuals save and invest money without affecting their eligibility for certain public benefits, such as SSI or Medicaid. For many of you, it can be an essential financial tool. To learn more and understand if you're eligible to open an account, visit ablenow.com and you'll find that link in today's show. Notes my conversation with Dr. Conti is not a brief conversation, but I believe it's an important one, so I'm sharing it in its entirety. And in the interest of full transparency, I want to remind you that the opinions expressed during our conversation are our opinions alone. In a moment, you'll meet my guest, Dr. William Conti. On December 24, the FDA issued a complete response letter, known as a crl, to drug manufacturer Sanofi, declining to approve the application for their investigational disease modifying therapy, tolebrutinib. Given the positive outcome of the Phase 3 clinical trial for tolebrutinib among people with non active secondary progressive ms, this came as a shock not only to Sanofi, but to most everyone in the Ms. Community. Now, Sanofi has announced that they're going to continue working with the FDA to find a path forward for todobrutinib. Meanwhile, joining me today is a guest who is right at the center of this highly controversial decision. Dr. William Conti is an Ms. Specialist and researcher. In fact, Dr. Conti was a principal investigator for the Hercules clinical trial, which was the phase three study of tolebrutinib. Dr. Conti recently wrote a powerful and candid essay titled the FDA's Complete Response was Leaves Secondary Progressive Ms. Patients with Nothing. In his essay, Dr. Conti challenges the FDA's logic and advocates for the people living with secondary progressive Ms. Who are literally running out of time. Welcome back to the podcast, Dr. Conti.
- [05:31]
B
Hi John, thanks for having me.
- [05:33]
A
You begin your essay by saying that being shocked by the FDA's letter was an understatement. As a neuroimmunologist who treats people with progressive Ms. Every day, why did this specific decision hit you so hard?
- [05:49]
B
Yeah, I think it was twofold for me. One was, you know, a year or two ago there was all this excitement over the, you know, the high end results from the Hercules trial being the first drug that was statistically significantly better than placebo for confirmed disability progression or in a population designed around secondary progressive Ms. And as we know, it's the main driver of disability long term in Ms. You know, I've always said publicly, I think we've kind of figured out relapsing Ms. These days the big unmet need is the progressive patients. So there was initially a shock first and foremost of, I sort of felt confusion initially about, because there had been a lot of messaging from the FDA in the prior, in the months in late 2025 about delays with the approval process. And my understanding was just the prior week before this announcement, the FDA had announced they needed more time to review it. But then they come in and say they've issued a complete response letter. So it was kind of like a 180. There was also some messaging about like fast track status, new disease designation earlier in the year for the NRSP Ms. Indication. So it's like, why would you come up with those things and then come back? So initially it was a big confusion. Then in early January, I actually was able to access the actual complete response letter from the FDA website. And then I just, I actually was angry after reading it by some of the statements that were made by the committee compared to other science based, you know, literature that have come up over the years. It was just a little, it was quite, I was quite angry initially was my first emotion.
- [07:52]
A
Well, we're going to talk about some of that science based literature that has come up over the past and, and, and how it compares with what has recently been decided. One of the things you mentioned in, in your essay is you're writing from the perspective of a clinician watching patients worsen while waiting for therapies. For our listeners who may not be as familiar with secondary progressive ms, can you explain the unmet need that tolebrutinib was meant to fill?
- [08:22]
B
Yeah. So for, for those that don't know, progressive Ms. Is a phenomenon in the Ms. World of slow accumulating disability over time. So the science has shown early on in at least relapsing Ms. You know, we see a lot of these inflammatory relapses, which are these new symptoms that happen very dramatically and acutely. But then patients get better over time after they recover from the relapses. Right. And then the disease modifying therapies are effective in preventing those relapses. And so why do patients get worse with Ms. Is, you know, there's a lot of terms that are thrown around, but the consensus is there's two distinct things that are happening, and they're probably happening at the same time, just in different proportions. So there's something called relapse associated worsening, which is raw. That's what I was just talking about with the relapse is. Right. So when you get relapse, you get worse. But unlike progression, which I'm about to talk about, usually there's some improvement. Maybe not 100%, but there is some improvement. And then there's something called pira, or progression independent of relapse activity. It's literally what it sounds. What it is, what it sounds like, where people are getting worse despite not having any relapses. Right. And so that's really the unmet need. Is that right? So both are contributing to disability progression over the long term. I think the relapse reduction has done really well over the last decade with the higher efficacy therapies. I mean, patients aren't relapsing anymore. And the usual story we hear in the clinic is, oh, I'm on a B cell depleter for the last five years. No new relapses. MRIs look stable, no side effects. But why, why am I feeling slower? Why is my walking slower? Why is my fatigue getting worse? And we hear that, I hear that almost on an hourly basis with patients, like, all the time. And it's, It's, It's. That's what progression is. And, you know, I think it's really, only really become very prominent recently because of the advent of the high efficacy therapies, as we pretty much stopped relapses. What remains is disability progression.
- [10:33]
A
Well, I'm glad you mentioned progression independent of relapse activity, because one of the most striking parts of your essay is your response to the FDA labeling progression independent of relapse activity, or pera, as quote, an emerging construct.
- [10:50]
B
That was bizarre to me when I read that in the crl, because, I mean, we've been talking about this for decades. It's been happening since the discovery of Ms. In a way. We just didn't have a term for it. Right. And it was just really bizarre to say it was an emerging concept. So, you know, on the one hand, yeah, I mean, it is kind of a newer concept in relapsing ms, but it's not like we came up with it yesterday. I mean, it's, you know, it's been fleshed out. So, you know, in my article, I talk about how in their letter, they talk about Dr. Fred Lublin's paper back in 2014, which is the traditional definitions of what he graphs it out and it was kind of like an opinion piece in a way from him. And I think it's a good paper. It just was. I mean it's from 2014 at this point. And since then, you know, the B cell depleters have been FDA approved. So you know, a lot of the higher mavenclad got approved since then. So a lot of these higher efficacy therapies have come to market. So we, when I say we like talking about the neuroimmunology community, have sort of, you know, I, I want to say moved on from that paper in a way. But you know, in, in 2024 there was actually an international consensus paper that was published which actually pulled in experts from all over the world to sort of come up with, well, let's call this that, you know, and, and let's get all the terms squared away because already in this interview I've thrown out, you know, progression relapse, you know, some patients talk about exacerbations. What does that mean? You know, and pyra and smoldering Ms. Right. There's all these terms that are thrown around. They, a lot of them mean the same things. But this consensus paper came out after this big meeting and it's, they just ignored that and it was just a little bizarre to say. I mean they literally said in their paper, in their letter that non relapsing secondary progressive Ms. Was not mentioned in Dr. Luplin's paper, which is true, but that was 12 years ago and there's been a lot of research since then.
- [13:00]
A
Exactly. So how does using old definitions, the way the FDA chose to use them, how does that affect the way that new innovative drugs like tolebrutinib are going to be evaluated today?
- [13:16]
B
Yeah, it raises up a lot of questions because, and I have to be careful what I say here in a way of I don't fully know what goes on on the back end is that my understanding of how these huge phase three trials are run is that these regulatory agencies, by that I mean the fda, the ema, whatnot, in all these countries, they have oversight over these studies in some way, shape or form because you can't really run a trial without vibing with what the regulatory agencies will accept, if you will. So there is a little give and take in a way. So if they're saying it's a quote, emerging concept, one, why did they create that term on their side of things earlier last year? And then two, why was the study approved to go forward in the first place? And it brings up even more Questions about other studies that are ongoing right now that use this terminology called non relapsing secondary progressive Ms. This wasn't the only study ever performed looking at this like, there are active phase three studies going on right now using the same inclusion criteria and terminology. So like, what about those studies? You know, it almost seems like a little bit like reinventing the wheel in a way.
- [14:35]
A
It does. Or reinventing it to the way the wheel looked 10. Yeah, I guess 20 years ago.
- [14:42]
B
Yeah.
- [14:44]
A
The FDA questioned the primary endpoint based on a small group of patients with asymptomatic enhancing lesions. In your article, you called this a moot point. Can you explain why that distinction is so important when we're considering the progressive Ms. Phenotype?
- [15:02]
B
Yes. So personally, I generally agree that, quote, enhancing lesions generally would go against progressive ms, and I'll tell you why in a second. But the way the study was designed, in my opinion, accounts for that. So usually progressive ms, we see something called neurodegeneration in the brain and the spine rather than inflammatory activity. So the inflammation is peripherally. It's thought to be peripherally derived. What that means is it's stuff in your blood that goes into your brain or spine causes inflammation. Right. That's what predominates. Relapses. You know, it's all very confusing about what's going on. But the idea is that progressive Ms. Is more of this slow neurogeneration of like brain atrophy, slowly expanding lesions, et cetera. So usually we don't see those changes on a sort of year to year mri. Those are slow processes, enhancing lesions. That's when you're given the contrast at your mri. And generally those show breaks in the blood brain barrier, which would imply it's something coming from the blood. Okay, so generally I agree with that overall concept. The issue here is one, enhancing lesions. What does that even mean? Like, I don't think the paper even talked about what those meant because, you know, we don't know. Right. So there's so much science still to be determined about what is driving progressive Ms. In a way, are these truly look like not all enhancing lesions are created equally is what I'm trying to say. Right. There's a difference between some subtle peripheral enhancement versus like a large brand new lesion. Right. So were these enhancing lesions on preexisting lesions? For these enhancing lesions on new T2 lesions? Like these are questions that I can't answer. All I know is that the data just says enhancing lesions at baseline by that topic, yes, there should be some Questions about it. However, the inclusion criteria for this trial, which is public information, you can't have had a relapse in the prior two years before the trial was screened, meaning the patients were worsening not because of relapses, but because of this disability progression. My point I was trying to make about being moot is to date, the FDA has resisted defining disease activity by biomarkers, aka MRIs. Right. All clinical trials to date, especially for relapsing MS, they define relapse clinically. MRIs are secondary endpoints. Even though. Right. Why are you getting new lesions other than disease activity? That doesn't count. If it's an asymptomatic lesion in a phase three relapsing trial, that doesn't count as a relapse based on the clinical criteria. So by pulling that whole idea in, are we now saying that they're accepting MRIs as a biomarker for, you know, primary endpoints? It's a little confusing in a way. We also don't know anything about those patients. You know, they start asking questions about what their MRIs look prior to the study, which I'm like, well, that wasn't part of the inclusion criteria. So.
- [18:21]
A
Right.
- [18:22]
B
I mean, inclusion criteria was clinical because the primary endpoint was clinical. And then I got really annoyed when this whole thing, because the only other FDA drug approved for progressive MS, which is actually primary progressive MS, ocrelizumab or ocrevus, actually had 30% of patients in their phase three trial that had enhancing lesions. And lo and behold, it's FDA approved right now. Why the change?
- [18:48]
A
That is a very good question that you raise. One person in this clinical trial died, and the FDA's concern really seems to center on this single fatal case of drug induced liver injury. You noted in your essay that other approved Ms. Drugs have had higher rates of liver issues, although perhaps not fatal ones. I'm wondering, is the FDA holding Tollebrutinib to a different standard?
- [19:15]
B
It seems like, in a way, you know, when, when the CRL was announced, I immediately thought it was a safety issue that they found. And if you look at my article, I actually start with the whole thing about definitions of progressive Ms. And the MRIs, because that's what really was the bizarre part to me, I think, you know, most of the investigators I could speak for were concerned about this, this, this death due to drug induced liver injury. That's what dilly means. So first and foremost, I mean, we should never see this. This is a never event in a way, for a clinical Trial, you never want to see a serious side effect like this. And to say that it was drug induced liver injury, that means the investigator wasn't me, but the investigator at that site determined that the injury was related to the study drug, not some other reason. That being said, and I said this in my article, I do think there needs to be some more transparency around that patient who unfortunately passed. Just other risk factors and whatnot. You know, the company was going to put in something called a REMS program which they enacted the more judicious liver monitoring when this, when this case happened. Right. So in the trial there's actually a partial hole almost for a year for them to rethink things around safety monitoring. In the trial, the point the FDA was also making was that there were not five other cases of diffuse a drug adduced liver injury in the trial that did not pass. And then therefore they're saying that's higher than to be expected for a trial drug. And they're talking about, they talk about this high's law, which is basically showing that the liver enzymes went up and also something called bilirubin, which is what makes people yellow when they have a liver injury. They're using that threshold, which is standard of practice. However, they then start talking about how even after the more frequent monitoring occurred, there were cases meaning heis law. However, my point was none of those patients progressed. They were, they were reversed. Right. So that means that shows the power of the more frequent monitoring is that it is reversible. Totally brute. And that makes sense based on how the drug works. The drugs actually has a very short half life. Half life means how long it takes for half of the drug to get out of the body. And the fact that weekly lab monitoring and whatnot detected these liver cases and then they recovered when stopping the drug goes to show the reversibility of this when caught early. I do think there needs to be some more information about the one case that passed, unfortunately. But stuff happened. This isn't the first time patients have died in Ms. Clinical trials. Let's just say that it's just, you know, the fact of the huge unmet need is sort of my thing of like, you know, we learned part of doing research is to learn about the drug more. Right. You know, you can't put patients in a test tube. Right. You can't be 100% clean and ignore all other factors in an individual's life. In these trials they try their best to control for everything, but you can't. And so the fact that they learn from this is really important. They then go on and talk about something called Temple's Corollary, which I also thought was really bizarre, where they were saying, I think it was like 3.6% had three times the upper limit in normal of the liver enzymes. What that basically means is when you look at your chart and you look at a lab test, there's a range, let's say 10 to 50 is there is the normal quote range for a test. 3x upper limit of normal means that you look at that top number, that's My example is 50 and you multiply by 3, 1, 50, right? That's three times the upper limit of normal. So let's say a blood test goes above that, then you meet three times the upper limit normal for. For their. For tip of corollary. It's based on the liver enzymes, but they're saying that it was high. But there's other currently approved drugs for Ms. That were much higher than the number that totally breathed in the pap. So I was like, why, why the shift? So concerned about safety. And it's just, you know, and I then bring up a point about, you know, what is the risk of doing nothing with these patients? And I talk about this with patients all the time all across the Ms. World. You know, a patient comes in, let's say newly diagnosed, you know, they look at the side effect profile that's on the Internet or on the label for these drugs and it's very scary, right? I mean there's some scary ass that these drugs can do, right? I mean life is scary and you know, these one in a million chances stuff, right? So I always tell patients, look, the lawyers get involved, right, with these labeling, right? Because you got to mention everything that happens, right? When you get the lawyers involved, you know, you're going to get really scared, right? You know, you listen to the commercials like, oh, this drug may cause you to die. Like, oh, well that sounds alarming. You know, especially in a field like ms, you know, chronic neurologic disease, you know, you, I always tell patients what is the side effect of under treating your ms? Because we're concerned about a very rare serious side effect. And I'm not trying to minimize side effects of drugs, but the newer, at least the newer high efficacy drugs, the. I always talk about the risk benefit ratio, right? You want, you want low risk, high benefit, right? There's never such a situation as 100% benefit and 0% risk, right? That doesn't exist. So. But what is the side effects of undertreating your ms? Right. If you're fearful for some sort of side effect with the drugs and you undertreat your Ms. 20 years down the road, now you're like disabled. Should we be thinking about that as a side effect? In a way. Right. And so by not approving this drug, now patients are left still without nothing. And so like I was really upset, you know, there was a lot of delays with the FDA last year with this and we had patients like asking about left and right, you know, like, look, in December we'll have more updates, January we'll have updates. We're kind of like, you know, kept delaying things and now like feel bad for patients, like my, for telling them, almost like leading them on in a way of saying like, oh, we have this new option coming out. And I was like, oh, never mind, I guess we'll keep playing this game.
- [26:00]
A
Well, everything as you were talking about what someone with Ms. Is willing to risk based on what the potential benefit can be. And, and you have pointed out a few times how there are other drugs that have some significant risk. If you read the fine print. I can, I can. What you reminded me of is the situation I lived with at home. My wife had a very aggressive case of Ms. And she was actually given a treatment that she absolutely agreed to that they tell you up front this has cardiac toxicity attached to it. In other words, your heart could stop. And so since nobody wants that to happen, you can only have 11 doses of this therapy in your lifetime. Now that sounds like quite a risk, especially when you're getting up to dose 10 and 11. Right. And I'll tell you, there was no hesitancy on her part because she lived with the consequence of not having a treatment available to her. So everything you say, just obviously you see patients every day. You know how true this rings. Let me circle back to the frequent monitoring program that Sanofi did put into place after the incident with liver damage. As someone who does see Ms. Patients in the clinic, do you see a weekly monitoring schedule as something a patient is going to be able to adhere to?
- [27:49]
B
Yeah, I mean, so that, I mean, that's a lot of blood testing. Obviously it's not the first time though. We've had frequent lab testing with an FDA approved drugs. What comes to mind is Lemtrada, which also is made by cnfe. So it's not their first rodeo with frequent blood monitoring. But that drug, if you go on Lemtrada, you have to get monthly lab monitoring for five years after treatment, after exposure. Really. And I mean, that's a lot of blood monitoring. And I remember once, I mean, when the drug was supported more, the company just had sent out people to the homes to draw the labs, like they would just pay for it to do it. And like, so, like, that was a great resource. I mean, as the drug got, you know, most profitable, I think that kind of stopped and you know, we had to do it ourselves. But it's not without precedent. Gilenia, you guys all remember that. And really Also the other S1Pmodulators, they have some requirements before starting and the companies generally, I think still will send people out to the house to do some of the baseline monitoring for those, you know, so it's a lot. I. It's a lot. It wasn't going to be one weekly testing forever. It was really at the first start because they did find in the trial all the cases were early on after exposure. But it's not our first time. I mean, that's sort of like our responsibility as the treaters in a way to figure this out for patients in a way. I can't just be like, oh, you can't get the monitoring. Oh, well, we have to figure it out. It might not be for everybody. Right. I'm not saying this is a slam dunk situation. And that's sort of the struggle as Ms. Specialist is figuring out, well, what is good patient selection for a certain drug and are they able to get, you know, because if the patient can't take the drug for whatever reason, they're not going to benefit from it. So sort of that same line.
- [29:58]
A
I want to talk about a slightly different aspect of, of the FDA's letter. They, they express concern that 25% of the study population had never been treated before. You link this specifically to underserved groups. Why does the FDA skepticism on this point risk further marginalizing those people who already face barriers to care?
- [30:24]
B
Yeah, I was a little like, not sure what their point was with that. They try to say that, well, the typical, quote, secondary progressive Ms. Patient has been on numerous treatments before, which I'm like, I mean, I guess, but that's definitely not true. I mean, I see. I mean, I'm in an area where there is a lot of barriers to access. You know, it's, there's a lot, we hear this all the time when I, when I'm seeing a patient of like, I mean, I literally ask, when I see a new patient, I ask like, oh, when were you diagnosed? What year were you diagnosed? And they say like a year. I'm like, okay, well when did your symptoms start Right. There's. There's always like a decade between when the symptoms start and, you know, where the formal diagnosis was made. We see that all the time. You know, just a few weeks ago, I had a patient come in with new quote, nuance ms, and then she's like, oh, yeah, they said I had a lesion like five years ago. I'm like, oh, what'd they do about that? Nothing. Like, what do you mean? They said it was like a migraine or something, or else stress. I was like, oh, that's interesting. Didn't know stress could cause lesions. But anyway, so, yeah, I mean, we see this a lot. I mean, where. Oh, yeah, you know, I was like, stumbling for a few weeks. I just chalked it up to like, low back pain or a knee issues. And they got better. Right? You hear that all the time. Where, you know, one. At the most benign level, a patient minimizes their symptoms because why would they think they have a, you know, potentially debilitating neurologic disease for whatever symptom, but other patients, there's this whole concept of, well, is the first disease activity even symptomatic? Right. You know, sometimes we pick up Ms. For patients that have no symptoms of Ms. Right. And those I actually say are the unlucky ones. In a way. I think it's, it's the best situation when your first lesion forms, you get a dramatic symptom because then you're able to like, be like, oh, something's wrong, let's go to the hospital. Right. It's, it's, it's more often we see these insidious onset of symptoms. That's the most benign story, the worst case scenario, and I see this a lot with my underserved patients, is that, you know, worse, they're gaslighted into saying, no, it's something else. Not a mess too. They'll know they don't have the medical literacy to think that, oh, it's a neurologic problem to sort of, you know, describe their symptoms in a way to whoever they're talking to. That makes sense. Right. So there's this whole sometimes disconnect between a healthcare professional and a patient about literacy. See, sometimes patients, like, they just can't explain their symptoms well, especially with Ms. Right. And sometimes I'm like, look, stop saying pain to me. Describe it. Use some more adjectives. Just don't say numbness, just tell me about it. Like, and sometimes, like, then when you really get into it, like, oh, yeah, that this is what it is. Right. You know, and, you know they have headaches. Don't say headaches, just describe it, what it feels like. And, and sometimes it just takes some teasing out sometimes. And that's where we see stuff, this delay in diagnosis all the time. And so While I agree 25% is, I mean, yeah, I mean it's a little bit unusual. Also, we have to remember this is a global trial where not all patients in certain countries have the best access to care across the board. Right. This is not just a US study. Even if it was a US study, it would have been a national study with different areas. I don't think it's impossible to claim that 25% baseline were naive treatment are not secondary progressive Ms. Again, the strict criteria for being in the trial is that you had to have disability, documented disability progression and no relapses based clinically. Right. So that was the criteria.
- [34:21]
A
You concluded your essay with a hope that the FDA committee can be educated on modern Ms. What's the most critical lesson they need to learn?
- [34:32]
B
I think, yeah, that's a good question. Obviously there needs to be some more ideas around this progressive phenotype. I actually tried with patients not to use the term secondary progressive Ms. In a way I don't think over the last few years to even decades. There's different schools of thought about does relapsing Ms. Transition to secondary progressive ms? Is it that progression's always there from the get go is just that lower numbers early on.
- [35:04]
A
Right.
- [35:05]
B
So there's a lot of thoughts around that and opinions. You know, I'm of the opinion that a Friday afternoon you're not relapsing Ms. And a Saturday morning you're secondary progressive Ms. Right. Like, you know, there's going to be shifts in how things work and you know, I, you know, if they wanted to choose the word emerging, I mean, I guess we're not 100% sure which it is, I guess, but it's still happening. Right. And that's what this study design accounted for. It doesn't matter. When the secondary progressive Ms. Quote started, it said it was happening to be in the trial. Now I actually like, I like I was about to say, I don't usually try to use the term secondary progressive with patients. I think it's negative label. People are like, oh, that's really bad. I'm like, I mean it isn't, it isn't. I mean it's bad in that there's not an FDA approved drug for it. But you know, just like relapsing ms, there's many different types of secondary Progressive Ms. In the way of like, oh, it could be very slow or it could be really fast. We just don't know. And it's very individual because it's happening. What you see with one person with Ms. Doesn't mean it's happening with you. I like to use the term progressive Ms. You know, there's relapsing Ms. And progressive Ms. I put people in these buckets and, you know, maybe that's not helpful for the FDA to hear. You know, they're probably very like, you know, the lawyers get involved, right. So they have to be very strict with the inclusion criteria. But that's what I say. I mean, if they're, if they're having this issue with this phenotype definition, just go back to this trial design, look at the inclusion criteria. Maybe we just need, if you want to stick with clinical, just say, make the indication for patients with Ms. That have not had a relapse in the prior two years and are progressing. Like, don't even use the term SPMS then, if that's the hold up here. Right. Like, you know, it's just, I think a lot of these discussions are kind of academic in a way. Right. Like, you know, it's sitting around the table talking about terminology, which is important, but it forgets what's going on in the clinics, you know, and that's what I say. And I just think the context around safety, I mean, I get, I think reading between the lines, there's some concern about is it that efficacious for this population versus the safety concerns. And I would just recommend, like, go back to what I said about what is the risk of doing nothing? You know, I think all in all, most patients would take a small risk of drug induced liver injury, given the stakes, what's at stake?
- [37:49]
A
Dr. Kadi, thank you for not only what you do to support the Ms. Patients you see in your practice, but for supporting everyone living with Ms. Through your advocacy. Thanks so much for talking with me today.
- [38:01]
B
Great, thank you.
- [38:03]
A
That's going to wrap up this episode of Real Talk. Ms. Real Talk Ms. Is powered by the National Ms. Society and you can share this episode of the podcast by letting your friends or family members know that all they have to do is point their web browser@realtalkms.com 440. You'll find that link in today's show Notes, so you can easily copy and paste it right into an email or a text. I hope you join me for next week's episode of Real Talk miss When you'll meet some of the experts who are here in San Diego presenting their research at the 2026 Actrooms Forum. I'm John Strum. Thanks for listening. Stay safe and make healthy choice. It.