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Dr. Howard: 

This is CME on ReachMD, and I’m Dr. Chip Howard. Here with me today is Dr. Nicholas Silvestri.

Nick, what can you tell us both about the FDA-approved and investigational FcRn antagonists that have shown both efficacy and safety in the management of myasthenia gravis?

Dr. Silvestri: 

Thanks, Chip. Yeah. I mean, this has been an exciting time the last several years for our patients in terms of other treatment options. Back in late 2021, efgartigimod was the was the first FcRn antagonist to be approved for the treatment of generalized myasthenia gravis in the United States. Efgartigimod, again, is an Fc fragment that binds with a higher affinity than native Ig to the FcRn receptor, and what it does is reduces IgG levels, including pathogenic IgG levels, in this case of the acetylcholine receptor and other antibodies causing myasthenia gravis.

And the ADAPT trial is, well, you well know, was the phase 3 randomized controlled trial of efgartigimod in the treatment of patients with generalized myasthenia gravis. And that showed statistically significant and clinically meaningful improvements of efgartigimod in the treatment of gMG based on the primary outcome measure, the MG-ADL [Myasthenia Gravis Activities of Daily Living scale], as well as several key secondary outcome measures, including the QMG [Quantitative Myasthenia Gravis score], in terms of response to treatment with efgartigimod.

Thankfully, also, the medication was fairly well tolerated, with the most common side effects being upper respiratory tract infection, urinary tract infection, and headache. So efgartigimod has been available now for several years, both in intravenous form, which was the source of the ADAPT trial, but also subsequently in a subcutaneous form, the efficacy of which was confirmed in the ADAPT-SC trial.

There’s also another FcRn antagonist that’s been approved; that’s rozanolixizumab. That was approved in 2023 on the basis of the MycarinG trial. Like the ADAPT trial, the MycarinG trial was a randomized, double-blind, placebo-controlled trial, which also showed benefit of treatment with rozanolixizumab based on metrics. Again, similar metrics to MG-ADL and the QMG compared with standard of care and placebo in patients with generalized myasthenia gravis.

Rozanolixizumab is delivered as a subcutaneous infusion, and whereas the cycles of treatment with efgartigimod, either intravenously or subcutaneously, are 4 weekly infusions or injections, that with rozanolixizumab is 6 weekly infusions per cycle. And the dosing of both of these agents was very novel in the trials; they were dosed cyclically, which is typically how we dose them in practice, though I still think, several years later, we’re still trying to get a handle on the appropriate dosing for these agents. But what’s exciting is they offer individualized dosing for patients, which is, frankly, what patients asked for when they were asked for their input, again, as you well know, into the construction of these trials and the design of these trials.

There are a few other FcRn antagonists in development. In fact, nipocalimab demonstrated efficacity in their topline results in the Vivacity-MG trial, the results of which were released earlier this year. And there’s another agent in development, batoclimab, which is currently in a phase 3 trial, and we are awaiting results, I believe, which will be out next year.

Chip, I’ll pass it back over to you.

Dr. Howard: 

Yes. The FcRn class clearly has had an impact on our treatment capabilities as being relatively safe, of varying durability, and in one of my patients, 42 weeks before we had to re-treat her. And so patients’ specific therapy may well be what we can do with this. The true dosing cycle though, I think, still has to be worked out.

Dr. Silvestri:

It’s important to know that though these agents are all of the same class, that being FcRn antagonists, that there are some different nuances, right? So I mentioned earlier that efgartigimod is an antibody fragment, whereas the remainder of the agents that we’ve discussed, rozanolixizumab, nipocalimab, and even batoclimab are full-on monoclonal antibodies. So there may be some differences here when it comes to pharmacokinetics, pharmacodynamics, as well as potential off-target side effects that can be seen with use of these different agents.

Dr. Howard

Well, with that, our time is up. Thank you for a great discussion, Nick. And thanks to our audience for tuning in.