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Cognitive Health and Sphinogine-1-Phospate Receptor Modulators in Multiple Sclerosis - Episode 14

Emerging Therapies and Future Directions in MS

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Heidi Crayton, MD; Jacqueline Nicholas, MD; and Flavia Nelson, MD, share their excitement for the future of multiple sclerosis treatment and comment on emerging therapies.

Stephen Krieger, MD: Treating MS [multiple sclerosis] is not a solved problem. And as excited as we are to have so many medicines that work and for which we have good data, there are entire new classes of medicines under review and that are emerging. I’d like to hear from each of you what you’re sort of excited about for the next step in MS research and potential treatment. I guess I’ll start, to say that you can’t go to an MS meeting nowadays without hearing about research on BTK [Bruton tyrosine kinase] inhibitors, which is, I expect, going to be the next entirely new class of treatments, at least new in our field. There are quite a few of them that are in clinical trials at the moment. These include medicines such as evobrutinib, tolebrutinib, fenebrutinib, and remibrutinib. I think I’ve probably forgotten a couple of “brutinibs.” But we are doing some of the trials at Mount Sinai Hospital, New York, New York, in nonactive progressive disease. They’re ones that tolebrutinib are involved in. The “evobrutinibs” are looking at relapsing MS and may be furthest along. I’m interested to see where this goes. I kind of want to do a quick poll of all of you and see what you think and what has struck you about these molecules to date. Dr Crayton, maybe you first. Anything in the BTK world that you’re interested in?

Heidi Crayton, MD: I’m cautiously optimistically that we have a tool in our arsenal to attack smoldering MS. That’s going to be the new buzzword, I think. And that would be incredibly exciting because that’s certainly been an unmet need. And I think that people who have had MS for quite some time or who have that kind of steady decline without changes on an MRI scan have certainly missed out on treatment opportunities that make a difference. I think that that’s incredibly exciting and I’m, again, cautiously optimistic that they’re going to be game changers. I’m really hoping so.

Stephen Krieger, MD: Alright, I’ll take your cautious optimism. How about you, Dr Nicholas, what do you think?

Jacqueline Nicholas, MD: I’ve regularly been accused of being overly optimistic at times, but I think we need that in the world of MS. But I’m incredibly excited about this class, for a number of reasons. As Dr Crayton mentioned, we’ve got good CNS [central nervous system] penetration, and I think the most exciting thing really will be if this can make an impact on neurodegeneration and get into those chronic, smoldering legions that we really haven’t been able to penetrate well, and impact folks early on. Thus, I wonder, and again, maybe overly optimistic here, will that, if started early enough, make a major impact on that long-term progression that we see even if we’re controlling inflammatory disease. I think that it’s always exciting when we have more options being studying in progressive MS because of course that’s a great unmet need. And then, I think from a safety perspective, I’m also optimistic because I hope that being a bit less, you know, not depleting B cells, but rather suppressing them will result in less infectious risks. And I think over time with some of our anti-CD20s, that’s one of the challenges that we’ve faced. Hence, time will tell.

Stephen Krieger, MD: Agreed. Alright. We’ve had cautious optimism, the accusation of being overly optimistic, Dr Nelson, what do you think, particularly with the angle towards smoldering MS, crossing the blood-brain barrier to do work within the central nervous system, what do you think?

Flavia Nelson, MD: I’m not as optimistic as my colleagues. I have to say, I’m excited for the possibility that we may be able to change what we call smoldering MS or progression. That we actually may have an effect on slowing progression more than what we’ve seen with previous drugs. But as you know, that’s a very complicated process. And I think it’s very patient dependent. And just like cognitive impairment, it has a lot to do with reserves and plasticity and ability to repair. Thus, unfortunately, when we have a clinical trial and we have results, that’s not necessarily the real patients that we have that are more complicated. And thus, I am excited about the possibility, but not as optimistic. I always say, it’s not about which one is the best drug that we have, it’s about which one works for each particular patient.

Stephen Krieger, MD: That’s right.

Flavia Nelson, MD: We’ll see what happens in the real world after the clinical trials.

Stephen Krieger, MD: Well, we’ve got a couple of years. We’re not going to have those data quite yet.

Transcript Edited for Clarity