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BTK Inhibitors and Novel Approaches to Multiple Sclerosis

News Network | <b>American Academy of Neurology 2022: Multiple Sclerosis Highlights</b>

Robert K. Shin, MD, offered his perspective on the novel therapies being developed for multiple sclerosis, highlighting the potential of Bruton tyrosine kinase inhibitors for progressive disease.

Robert K. Shin, MD: I think one thing that's been happening in the MS space is that we continue to make progress in terms of our treatment options for multiple sclerosis. So it's been now, about a quarter century of therapeutics, but new classes keep being developed. And if we're honest, we keep getting increasingly effective at treating, at least, the relapsing form of disease. It does seem like there is an increased interest in also figuring out how we can prevent accumulation of disease progression over time.

I could say, as a general statement, that there has been a lot of interest in a new class of potential treatments for MS, the Bruton's tyrosine kinase inhibitors—the BTK inhibitors. We're hearing a lot about them. We're seeing posters and more research, preliminarily, as well as the recruitment for the next phase 3 studies to look at the efficacy of this class of medication. That's really what I've been most interested in, is seeing where we're going to go in the future. With BTK inhibitors, I think what's interesting—and maybe takes us to a place we haven't been before the MS space—is multiple companies are developing multiple versions of BTK inhibitors, more or less at the same time. Some products are a little bit farther in development than others, but it's kind of remarkable to see 4 or more BTK inhibitors being actively looked at and evaluated at the same time.

Now, I would have to say that although there's a lot of promise in this class, we don't know if it's going to pan out. For example, we are seeing in the earlier studies an effect on, let's say, MRI parameters, right? Those are markers of active inflammation, or if you will, markers that certainly typically correlate with the relapsing component of the disease. But the promise of BTK inhibitors, the possibility that they can act centrally on things like microglia, or do things that might reduce progression over time, perhaps treat the focus on compartmentalized inflammation or smoldering—whatever term you'd like to use for that. That promise has yet to be realized. We will have to find out.

Another challenge in evaluating the class of BTK inhibitors will be things like the tolerability of these medications. A lot of the studies seem to be showing a dose-dependent relationship, meaning the higher dose, the more effective the medication seems to be. But, also with higher doses, there is a potential for tolerability or safety issues. We've seen that in other spaces where BTK inhibitors have been evaluated other than MS. So, I would say it's exciting as a possibility, but we're really going to have to wait for the data to find out if they are all effective, if some are better than others, if some are effective in one way and others in another. This is yet to be established.

Transcript edited for clarity.