Progress in MS Therapeutic Development and Shifts in the Landscape

Robert K. Shin, MD: Actually, it's more than a quarter-century as I think about it, right? We're approaching 30 years—3 decades—of having approved therapies for multiple sclerosis. And some of the medications that were approved in the early 1990s are still being used today, which is kind of amazing. However, I think that with some of the data that that's been presented now, we're doing more and more head-to-head studies with active comparators. I think we can say that certainly for patients with active MS, we can see that there's a difference. That some MS therapies are more effective than other therapies, I think we should just be honest about that. They're not all created equal. And it doesn't really matter whether we focus on relapse rate or MRI parameters, disability progression, or combining them together into a metric like No Evidence of Disease Activity, whether it's NEDA-3 or, if you incorporate other components, NEDA-4. For the first time, we can say, Oh, if I use drug X over drug Y, I'm going to have a greater chance of seeing no evidence of disease activity.

I think that MS might be not totally unique, but unlike in some other fields of medicine, we have not agreed upon a firstline therapy. We don't have a consensus that when somebody is diagnosed with MS, we should start with drug X, and then if that's not tolerated. That kind of thing, which is common in other disease spaces. We just haven't come to a consensus in this space. But I think that if we look at studies that we're seeing reported out today, and what I think you can really see is that we should be honest and say that there are therapies that are more effective than others, there are strategies that will be more likely to result in shutting down of the disease process than others. Again, in our field, we're still debating sort of the timing of that optimization of our strategy.

But I do think that maybe there's an increasing shift, a recognition, that with the advent of therapies with greater efficacy, at least that option exists. I think more and more people are looking at using them earlier in the disease course rather than waiting until disability is apparent. And so to me, this is a positive shift. One thing I think that's kind of changed even how we think about MS, in terms of its clinical course, is the different disease processes. Because I do think in the past, we really thought in a very binary way. We thought that people would present with a relapsing form of the disease, and you know, heaven forbid that you transition into phase 2, like a progressive form of the disease. As if there's sort of this wide gulf between the two. Hopefully, you would never cross over in that regard. As we've seen at AAN and other meetings, data using different biomarkers, whether it's optical coherence tomography, serum neurofilament light, other biological markers, volumetric MRI, other more investigational MRI markers—what's the common theme? We're seeing that neurodegeneration occurs from the beginning of the disease process, if not probably before the patient's even aware or the providers are even aware of the diagnosis. I would say, rather than two different stages, we now see them almost as overlapping. We see that there is a progressive neurodegenerative component that is occurring, as best we can tell, probably from the beginning of the disease process that is punctuated by relapses.

My opinion of why we were, I guess, misled is because of the existence of reserve, right? The ability of a young healthy person to compensate for the early stage means that it created the illusion that everything was fine until reserve runs out, and then the progression is more obvious. So to me, this has been the biggest shift in our understanding of the disease process because what this means is that we are developing a heightened sensitivity to any signs of progression. In other words, rather than waiting until somebody suddenly needs to use a cane or walker, what's the focus? Everyone's interested in things like cognition and biomarkers and different things to recognize this component as early as possible, really setting the stage for theoretically, hopefully, another class of therapies that will be to be particularly helpful for that. So there's been this shift, I would say, in sort of our thinking about MS, which I find very exciting because I think this maybe bodes well for the future. But as we discussed earlier, there are still some important steps that are necessary before we'll know how to best address that.

Transcript edited for clarity.