James F. Howard Jr, MD, discusses both intravenous and subcutaneous efgartigimod for the treatment of gMG.
James F. Howard Jr, MD: Efgartigimod was the first neonatal Fc receptor inhibitor approved for use in generalized myasthenia gravis. It’s an Fc fragment, very small, not a full-size antibody. Administered intravenously weekly for 4 weeks. And then patients were observed in a clinical trial. The outcome measures myasthenia gravis, activities of daily living score [ADL], and the quantified MG score [QMG],…were substantially improved over the placebo arm. But it was our first insight into personalized medicine. Patients said, “We want to be treated when we need to be treated, not continuously.” And that’s why this cyclical dosing cycle was developed. And what it showed us is that not everybody responded the same way. More than half the patients had improvements in excess of 8 to 12 weeks. A third went well beyond 12 weeks. Eleven percent had 6- to 8-week improvements compared with the dosing that we used, for instance, with intravenous immunoglobulin, which is every 3 weeks. And so we found that some patients could go very long durations. My longest was 46 weeks, 42 weeks before they required retreatment. And that’s a huge benefit to an individual who doesn’t want to be taking a medication chronically and still have substantial improvement in one’s examination. And then it was determined that we’d like to develop a subcutaneous form of this. Preliminary studies were done to determine what effective dose subcutaneously would produce the same results in terms of immunoglobulin [IgG] reduction in clearance as the intravenous form, and that dose was chosen. And then a clinical trial and a noninferiority trial were designed to [randomly assign] patients either to IV [intravenous] or to subcutaneous administration using this weekly treatment for 4 weeks and then looking at outcome measures. And we found that the IgG reduction was virtually identical. AChR [acetylcholine receptor] antibody reduction was virtually identical. In addition, the clinical outcome measures of ADL [and] QMG were virtually identical as well. The [adverse] effects of intravenous efgartigimod, the FcRn [neonatal Fc receptor] inhibitor, were predominantly headaches, nasal pharyngitis, some diarrhea, and these 2 were seen in the subcutaneous form at very equal numbers. There were a group of patients who did have injection site reactions, typically a wheel flare, small rash. Interestingly, the more frequently they were injected, the less these became apparent. And in no case was the drug discontinued because of these ISRs [injection site reactions]. And so, it was a very well-tolerated drug, giving very similar efficacy to the intravenous form, and most recently was approved by regulatory agencies for the treatment of generalized myasthenia gravis. Now, the labeling says AChR-positive myasthenia, but the data show that those who are AChR antibody negative or negative MuSK [muscle-specific kinase], etc, had as good a response as those who had the antibody itself. The placebo arm of the AChR-negative population was much greater in terms of its response than the placebo arm in the AChR antibody–positive group, and therefore it negated any significant statistics. But many of us believe that it is as efficacious, and studies will be done to try to confirm that and prove this will be a potential capability for that population as well.
So patients ask me which is better? IV or subcu[taneous] for these preparations? And there is no right or wrong answer. It’s an individual choice. And in fact, we query our patients every few months [and ask], “If this medication were available intravenously or subcutaneously, which would you take?” And it runs 60% [and] 40% in one set. It’s one way, and several months later, it flips and goes in the other direction. It’s interesting that some of our older patients prefer IV infusions. I think they see it as a social event as they sit in the chair and talk to their neighbor in the next chair while they get their infusion. I think the individual who’s active, on the go, either for job or for play, prefers subcu[taneous], particularly if they can administer it themselves. So you pack it in your bag, and you go. And so I think these are going to be the traditional terminating factors. I have one patient, an ICU [intensive care unit] nurse, who refuses to inject herself subcutaneously, and she is giving injections to patients all the time. But she will not, nor will she allow her husband, to inject a very small, aqueous solution for her disease. Go figure. I mean, it’s this kind of personal choice. So I don’t think one form or the other is going to predominate, if you will, the market. I think it will probably split pretty close down the middle or a few percent, one way or the other, based on the needs at the time and the choice at the time of the individual.
Transcript is AI-generated and edited for clarity and readability.