FcRns Inhibitors for the Treatment of Myasthenia Gravis


James F. Howard Jr., MD and Nicholas J. Silvestri MD, FAAN, discuss the efficacy and safety of FcRn inhibitors, as well as consider their role in the rapidly evolving treatment landscape.

Dr. James F. Howard: What about the FcRns? What experience have you had in that?

Dr. Nicholas J. Silvestri: I would say so far so good; is a short answer. I've had several patients on Vyvgart over the past several months since it was approved. I think with any new drug there can be access issues early on, but I would say that wasn't a huge issue. I would say that so far, the payers have been pretty generous with approval and certainly in selected patients. These aren't de novo patients, at least not yet. And I would say my clinical experience really mirrors the findings of the adapt trial. I've had pretty robust responses from patients and occurring pretty quickly too as was the case actually with eculizumab. But I would say with Vyvgart patients, I would say we are noticing changes after one or two infusions. And still working on optimizing dosing. To be fair, I've only had patients on this drug for four months. But I think we will learn a little bit more, but I do to an extent like the customized dosing for patients so that we're not over or under-treating patients. But I do think it is nuanced and, for the appropriately selected patient, a nice way to go.

Dr. James F. Howard: Yeah. The interesting aspect, one of the interesting aspects of the trial was that rather than treating continuously, patients were paused. And the re-treatment criteria required an exacerbation of their disease almost back to where they were prior to getting that course of treatment. It's administered four weekly infusions. And what it showed when we looked at the durability of the response is the marked variability. Half the patients had improvement by their definition, which was an ADL responder. Two-point change sustained for four weeks with improvement occurring within one week of their fourth infusion. 50% had more than eight weeks of betterment. A third of them had more than 12 weeks of improvement, 11%, four to six weeks. The others were in between. But clearly shows you that this is not the same in everybody. And the message that when the trial was in design from patients and advocacy groups, et cetera, is that we wanted independence. We wanted freedom. We don't want to be dosed on an ongoing continuous basis. Will that be used in the future? I think in parts is going to depend upon how payers allow us to use the drug. We're clearly not going to let patients relapse all the way back and then retreat them. We don't want peaks and valleys. We want gentle rolling hills. And so, is that best obtained with constant dosing versus this pulsed cycle dosing? I think only real-world evidence is going to show us that. Would you see FcRn inhibitors replacing plasma exchange and IVIG?

Dr. Nicholas J. Silvestri: I think it's possible. I think that as we spoke about earlier, at least my main use of plasma exchanges is a treatment for a crisis. I rarely, if at all, will use it as a chronic therapy. And there's a lot of reasons for that, but predominantly it has to do with availability in our area. But I would say for crisis, I don't know that FcRns, at least in my mind right now would replace plasmapheresis. Certainly, that's open to discussion probably even open to a trial. IVIG is a different story. I do think that there is a big chance or a high likelihood rather that FcRns could supplement the use of IVIG in the treatment of myasthenia. I would say that my experience with IVIG and myasthenia is somewhat variable. It works really well in some patients and other patients it doesn't work as well as it might in a disease like CIDP. And there's a lot of tolerability issues with IVIG as you well know. Many of my patients will have headaches or flu-like symptoms that can be really debilitating. And patients put up with it because it makes their myasthenia better, but if there was an agent that worked just as well, or maybe even better in some patients and didn't have those tolerability issues, that would be a fantastic welcome. I think to answer your question, to summarize, probably not replacing plasma exchange at least at this moment, but almost certainly replacing IVIG in vast majority of my patients.

Dr. James F. Howard: Yeah. I would agree with much of what you said in terms of crisis. And that's probably still reserved at the moment for plasma exchange until we have a trial. IVIG clearly for the reasons you stated. I have a stable of patients, particularly those that for whatever reason, we've not been able to transition to a complement inhibitor, for instance, who receive plasma exchange on a chronic basis, some as long as 10 years. It's the only way I can keep them out of a hospital. And I see something like this for convenience and logistics for the adverse event profiles. These patients end up with ports that we have to access. Rarely when you go that long do your veins hold up for just peripheral sticks and all. I see a rule there. In terms of adverse events, what's been your experience with both of these classes in terms of AE profiles?

Dr. Nicholas J. Silvestri: With the complement inhibitor is really not much of anything. I think that every patient that I've dosed with it has said maybe the first or second infusion they didn't feel great, but after that, they were fine. And knock on wood, I've not had any problems with them otherwise. And I think it's really too early to tell with Vyvgart. Very similarly, some patients, at least with the first infusion or two didn't feel all that great. But again, otherwise, they've been pretty lucky. In neither case have I seen infections in patients, which was the most common side effect in the trial, at least the FcRn trials but so far so good. I think that there's a lot of reason to be hopeful as we look forward to the future. We talked about therapies that are highly efficacious, but also, fairly well-tolerated and probably safer than some of the traditional agents that we've used.

Dr. James F. Howard: I would agree. Much safer than the traditional agents we use. And I think that's going to be a critical reason why we move to these kinds of targeted therapies. But real-world evidence is going to have to give us the true answers.

Transcript Edited for Clarity

Related Videos
Related Content
© 2024 MJH Life Sciences

All rights reserved.