Intravenous efgartigimod (Vyvgart) continued to show efficacy and safety in patients with generalized myasthenia gravis who did not have detectable anti-acetylcholine receptor (AChR) antibodies, according to open-label data from the ADAPT SERON trial, which was presented at the American Association of Neuromuscular & Electrodiagnostic Medicine annual meeting.
In this exclusive MedPage Today video, James F. Howard Jr., MD, of the University of North Carolina at Chapel Hill, discusses the implications for treating these patients, including evidence that some may require additional treatment cycles before experiencing meaningful improvement.
Following is a transcript of his remarks:
So those individuals who don’t have antibody to the acetylcholine receptor, particularly those who have no antibody that’s been identifiable either to the MuSK [muscle-specific tyrosine kinase] protein or LRP4 [lipoprotein receptor-related protein 4], are a population of patients that have been robbed, if you will, of the ability to be treated effectively with our current new targeted therapeutics that have come online over the last 10 years.
And so this is very important that we now have a therapeutic tool that we don’t have to hassle with, if I can say that term, with our payers. And while they represent a small minority of our total population, about 10%, they really deserve the best-quality treatment that we can provide. And this is the first avenue to do that. Because of it, we now have other companies who are looking at the seronegative population, or at least the AChR-negative population, in our designing trials. So, I think the future is bright for this group of patients.
The majority of patients who were in the original ADAPT trial responded very quickly. Within the first cycle, we’re seeing meaningful improvement. And it’s interesting that — and we don’t have the answer and the understanding at this point, it’s being looked at — individuals who do not have AChR antibody have a slower onset of effect that takes two or even three cycles of treatment before we start to see meaningful improvement. Where before or after two cycles, we’d say, if it’s not helpful, abandon, find something else. I think we have to be cognizant that we may have to wait a bit longer, maybe three, even four cycles, 6 months, if you will, before we say this is not working.
It’s important that we recognize those who will not respond because we don’t want to waste time. We don’t want to subject them to potential adverse events of a therapeutic that’s not going to be of benefit, but we can’t be quick to jump, if you will, in this seronegative population.
I think it’s our believing that because we’re seeing similar responses in those who have no antibody to anything, to MuSK, to LRP4, that antibody is indeed a driver in this autoimmune disease. Those who have AChR, we also have to deal with the fact that there’s complement activation that is destroying the neuromuscular junction architecturally.
That’s not true with MuSK. We don’t know for sure at this point whether it’s true in those who have no antibody, what we call triple seronegative, though there is basic science data that suggest complement is seen at those neuromuscular junctions. And we know that antibody activates the terminal complement cascade and turns it on, if you will.
So yes, the antibody is the driving force behind all of this. I think what we’ve also demonstrated is that safety is very similar. There are absolutely no new signals that we’ve seen in these subgroups of populations.
And we know that safety is very similar across indications, regardless whether it’s dermatologic, neurologic, etc, that we’re seeing very similar safety profiles, which is very encouraging.
