An expert neurologist discusses zilucoplan and other pipeline agents in the treatment of myasthenia gravis.
Ericka Wong, MD: Zilucoplan is a complement inhibitor, like ravulizumab and eculizumab. One of its benefits is that it offers subcutaneous administration, and a phase III trial of it is underway at this time. This is unlike efgartigimod, which is a neonatal Fc receptor inhibitor. The difference in terms of patient population is that because of the mechanism of complement inhibitors, they’re really targeted to acetylcholine receptor antibody-positive patients. Whereas for efgartigimod, because it decreases the IgG [immunoglobulin G] levels in the serum, it can be a little more broad. In the ADAPT trial, there were about 20% of patients who were either antibody negative or MuSK [muscle-specific tyrosine kinase]-antibody positive. In this trial, there was a suggestion that there is possibly clinical benefit with efgartigimod in these patients, but it will need to be further studied.
I think as providers, we won’t complain that there are more options available, and certainly with these newer, more targeted medications, the efficacy and safety profiles have changed the landscape of treatment for patients with myasthenia gravis. We don’t quite yet know what medication might fit what patient best. Like with many diseases, particularly myasthenia, a lot of our treatment is tailored toward the individual, their symptoms, their comorbidities, and things like that. I think we will still take that approach with seeing what medications work best with what type of patients. Even in these trials, you can see that there is quite a range in response of myasthenic patients. Time will tell in terms of what medications, for example, either the complement inhibitors or the neonatal Fc receptor inhibitors, which might work better for what type of patient. But I think at this time, we’re not sure yet, except that we know that the complement inhibitors are targeted for acetylcholine receptor antibody-positive patients.
There are several other neonatal Fc receptor inhibitors. Rozanolixizumab recently completed a positive phase III trial, and also nipocalimab is undergoing a phase III trial.
There are also the B-cell inhibitors. Notably, there’s an anti-CD19 and anti-CD38 drugs that are undergoing phase II trials. There are also the CAR [chimeric antigen receptor] T-cell therapies, which really transformed the field of hematology-oncology, that are being explored in patients with myasthenia gravis. These are undergoing phase I trials.
Transcript Edited for Clarity