Capturing Patients’ Experience in Their Daily Lives

One of the challenges with rare diseases is how different their effects can be from one person to another. In order to get a deeper understanding of the impact and variation of the rare autoimmune condition myasthenia gravis on people, Argenx launched MyRealWorld MG, an app-based study that’s collecting real-world, longitudinal data from 2,000 patients over two years. We spoke to Deb Gelinas, neuromuscular executive director at Argenx, about myasthenia gravis, the company’s MyRealWorld MG study, and how she hopes the data will provide new insights into the rare, autoimmune condition.

Daniel Levine: Deb, thanks for joining us.

Deb Gelinas: Thank you for having me.

Daniel Levine: We’re going to talk about myasthenia gravis, Argenx, and its international real world study of the condition and its impact on the lives of patients. Let’s start with myasthenia gravis itself, though. For listeners not familiar with the condition, what is it?

Deb Gelinas: Myasthenia gravis is an autoimmune neuromuscular disease driven by IgG autoantibodies that attack the neuromuscular junction. And when this occurs, it gives rise to weakness and functional disability. The weakness can affect many different areas. It may affect eye movements, it may affect speech or swallowing. It may affect your breathing, your arm function, or your leg function.

Daniel Levine: And how does the condition manifest itself and progress?

Deb Gelinas: Well, in the majority of patients, it starts as an ocular, or starts with your eye movements, and it may start with a drooping of the eyelid or occasional double vision. However, in 85 percent of patients, the condition will go on to generalize within two years. So, although ocular is a common onset, it doesn’t typically stay ocular.

Daniel Levine: I know there’s a reliable diagnostic test for the condition, but given its symptoms can align with many other conditions, how difficult is it to get a correct diagnosis?

Deb Gelinas: Well, if you are seeing a neurologist, it certainly is not impossible. Neurologists are very familiar with this condition because the hallmark is fatiguing muscle weakness so that the more you try to do something, the weaker you become. Typically, for instance, your voice may start off strong, but the more you try to speak, the weaker your voice becomes. Similar things may happen with regard to your limb function and your strength. So, in the setting of that fatigable muscle weakness, neurologists know to test for a blood test, which is an autoantibody myasthenia gravis panel, which is very quick to get a feedback result, and can be very definitive. Now, if you do not have an autoimmune antibody that can be identified, and in some patients early on the antibody level may be below the limit of testing so that it’s not detected. In that case, the neurologist may need to do electrophysiologic testing to see if your muscle is stimulated, when the nerve is stimulated, to see if your muscle responds less and less with repeat stimulation. That’s called a detrimental response.

Daniel Levine: I have confidence in a neurologist being able to diagnose this condition, but I’m wondering what it takes a patient to know to get to a neurologist. Do physicians typically refer them immediately? Is there a lag in, you know, looking at these systems? It’s something that indicates the need to see a neurologist.

Deb Gelinas: I think that it very much depends upon your access to medical care in general. I think that some patients with some payer systems probably have easy access to a neurologist. I think other patients maybe find it much more challenging and those patients may end up presenting to an emergency room because they may have extensive weakness by the time it is appreciated that they need to see a neurologist.

Daniel Levine: In December 2021, the U.S. Food and Drug Administration approved Argenx’ Vyvgart to treat generalized myasthenia gravis. This was the first in a new class of therapies. What is it and how does it work?

Deb Gelinas: So, Vyvgart has a very unusual mechanism of action in that we’ve known for decades that myasthenia gravis is driven by IgG autoantibodies. However, it’s been more recent that we have learned what controls the concentration of those IgG autoantibodies and we now appreciate that the concentration of the IgG autoantibodies or any IgG antibody in our blood system is actually managed by a receptor that is on our cells called the FcCRn receptor. Now if an IgG antibody is bound to that receptor, then the antibody will get recycled back out into circulation. If the IgG antibody is not bound to that receptor, the antibody will get destroyed so that our bodies have a natural homeostatic mechanism for managing the concentration of IgG antibodies. Vyvgart is using that natural homeostatic mechanism to actually increase the destruction of IgG antibodies so that instead of getting recycled back out into the circulation, fewer get back out into the circulation. And so, we actually with Vyvgart get about a 60 percent reduction in IgG antibodies. That is enough of a reduction to actually get control over myasthenic symptoms, but at the same time, not so much of a reduction that you’re going to end up with problems from not having enough IgG antibody. So, it’s a drug that has a very favorable risk benefit ratio with regard to how much it can give you control over your myasthenic symptoms and yet not give you terrible adverse events.

Daniel Levine: Does that compare to other therapeutic approaches?

Deb Gelinas: It’s very novel. It certainly was the first in its class. I think that it is going to revolutionize the care of myasthenia gravis. Typically for many decades when I first started practicing neurology and treating myasthenic patients, the only real way that we could control myasthenic symptoms was to use sort of a shotgun approach, which was just shut down the immune system on the whole. So, we would use very high doses of steroids. And in those days, although steroids are effective and they do help improve myasthenic symptoms, there is quite a cost, and the cost of steroids has to do with how much you use and how long you’re on steroids. So, over the years, I can honestly say I have been responsible for patients developing problems with glucose. I’ve been responsible for patients developing fractures because I was treating them with a medication that controlled their myasthenia, but at a high cost, not a high financial cost, but a high burden cost.

Daniel Levine: What’s been shown from the studies to date on Vyvgart?

Deb Gelinas: What’s been shown to date going by our trial, a randomized controlled trial, we were able to demonstrate that patients who had previously been managed with either symptomatic therapy, which is basically just trying to—I could say the name of the therapy, but it’s mestinon—that’s  symptomatic, only works for just a few hours, or patients who were on more definitive immunosuppressive therapy with steroids or with non-steroidal immunosuppressive drugs that are typically used, for instance, in cancer and other conditions. We were able to show that when Vyvgart was added to patients who were on either one of those medications or two or all three, that we were able to have a significant increase in control over the disease, both in improvement in strength, and in improvement in function.

Daniel Levine: Argenx is working on a study to gather real world data to better understand the experience of people living with myasthenia gravis. This is being done in collaboration with several patient advocacy organizations in several countries. Why are you conducting this study? What are you trying to learn?

Deb Gelinas: So, this study is actually something that we have been doing now for several years at this point. We have baseline information from 841 patients who self-identify as having myasthenia gravis. These patients have an app on their phone called the MyRealWorld MG app, and they’re able to self-identify and put in information with regard to how severe their symptoms are with regard to what medications they’re on trying to control their disease, as well as certain questionnaires that we ask, such as whether they rate their disease as mild, moderate, or severe, or even just purely eye, ocular MG. How they rate their function with their MG-ADL scale, their medications that they’re on, how they rate their quality of life. And we were able in many different countries to get some very interesting information based on these patients. We have information from Europe, U.S., Canada, U.K., and Japan. And we were really able to characterize just what the burden of myasthenia gravis is for patients.

Daniel Levine: This is a longitudinal study. How many patients are you ultimately seeking to enroll, and is there an time you would expect to conclude this study?

Deb Gelinas: So the MyRealWorld MG study—we have already published our baseline characteristics results from 841 patients, but this is actually a 2-year longitudinal study where we hope to have 2000 patients, and we hope to be able to obtain serial data in terms of how the disease is affecting patients with regard to their function, with regard to their wellbeing, their quality of life, and for them to be able to share information about how they’re managing it in terms of what therapies they’re taking.

Daniel Levine: How do you expect the data to ultimately be used and will Argenx be the only one with access to it, or will others also have access to this data?

Deb Gelinas: No, it’s research that’s open access so that we’ve already openly shared what we have in terms of the baseline data. We have been not keeping it to ourselves, but actually trying to share it with the MG community in order to be able to appreciate the magnitude of suffering that patients with MG go through. they suffer not only in terms of their physical strength, but they suffer in terms of the anxiety of having unpredictable symptoms, of being able to feel fully in control of their bodies one day and the next day to actually be so short of breath that they have to get to an emergency room and be put on a ventilator, for instance. This kind of lack of control over your function gives rise to tremendous anxiety and depression and an inability to actually fulfill one’s role in society, whether it’s your role at work, whether it’s your role as a homemaker, as a caregiver, so that what we’re hoping to do is to better characterize what the true burden is to a patient.

Daniel Levine: Have there been any surprising findings yet from the study?

Deb Gelinas: Surprising to me maybe, not because I’ve taken care of patients with this condition for many decades, but what we’ve found was that patients who self-identify as having more severe MG have more problems with diminished quality of life. They have more problems with their breathing, more problems fulfilling functional roles, simple household tasks, activities of daily living, holding down jobs, things like that.

Daniel Levine: What does making use of this technology and having close collaboration of patient advocacy groups on the project suggest about the changing ways biomedical research is being conducted today?

Deb Gelinas: I think more and more we want to hear the voice of the patient. I think that the days of going to the expert physician and saying, tell me about this disease, tell me what you think is the most oppressive symptom of the disease—I think those days are actually increasingly over. And I think now what we’re appreciating is something that honestly I knew—that my patients were short of breath. I knew that my patients were weak. I didn’t appreciate that my patients were anxious and depressed. I think that with this kind of outreach to patient advocacy groups and to patients themselves, we’re really hearing about the magnitude of how a chronic autoimmune disease like myasthenia gravis, how it affects function and happiness, and basically humanity and role in society.

Daniel Levine: Argenx has a broad pipeline across rare immune conditions. Do you expect this study to be a model for work you do in other areas?

Deb Gelinas: Very much so. We are seeking with every disease that we’re studying to really characterize, first of all, the burden of that disease on patients as they are being treated today in order to be able to see how our potential therapeutics can reduce that burden and relieve suffering.

Daniel Levine: Deb Gelinas, Neuromuscular executive director at Argenx. Deb, thanks so much for your time today.

Deb Gelinas: Thank you.

This transcript has been edited for clarity and readability.