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Bruton Kinase Inhibitors (BTKi) Use in MS Treatment


BTK inhibitor implementation for MS treatment is explored.

Ryan Haumschild, PharmD, MS, MBA: Now if we could, let’s discuss the emerging role of Bruton tyrosine kinase inhibitors [BTKis] in multiple sclerosis [MS] management. Because we have a lot of experience with BTKis, especially in mantle cell lymphoma and CLL [chronic lymphocytic leukemia]. We started with primary agents, and we have next-generation BTKis, and now we’re having reversible [inhibitors], and I think there’s so much innovation happening within the hematologic malignancy space. But we also know there’s a ton of innovation now that’s translating to multiple sclerosis. I think that’s exciting for our patients. The more innovative mechanisms of action and treatments we can provide, the better. I do want to turn to you, Dr Williams, as someone who’s staying on top of these new treatment options. What are some of the potential advantages of BTKis? What may they have over other treatments, such as monoclonal antibodies, in the landscape of multiple sclerosis? And if you could, talk about some of the advantages of some of these agents with CNS [central nervous system] penetration when we’re treating patients with MS.

Mitzi Joi Williams, MD FAAN: There is a lot of excitement around BTKis and their use in MS. Certainly some of the advantages are, it always is helpful when you have a compound there is some experience with, even if it’s in another field of medicine. You have some basics about the compound, adverse effects, etc, and how it performs in people. That gives often many of us as neurologists a bit more confidence because we’re often risk-averse ourselves when counseling our patients. I think the other thing that’s extremely important is that it’s targeted B-cell depletion. That’s exciting because ideally, we want targeted therapies that are effective but have better adverse effect profiles. Certainly the concern for malignancy is something we’ve seen with some of our other monoclonals, as well as opportunistic infections, so the thought of not having to deal with those specific adverse effects is very exciting. Then of course CNS penetration is one of the big pain points for many of our therapies. Often they do not cross the blood-brain barrier and work peripherally, which often leads to many of the systemic adverse effects we see with some of those therapies. So the thought that these therapies, many of them are CNS penetrant, is very exciting to see how we can impact the inflammation in the CNS. And can we do an even better job at preventing progression or slowing inflammation because there is CNS penetration?

Ryan Haumschild, PharmD, MS, MBA: Dr Hickman, if I can ask you, since you’re involved in a lot of these treatments, even from a pharmacy perspective and adverse effects and real-world evidence, what can we leverage from what we know about BTK inhibitors from the hematology space into MS? What are some of those things, as you start to treat these patients from a pharmacist perspective, you’re going to look to create better predictability of response or better management of the disease?

Amanda Hickman, PharmD, MPH, MSCS: Absolutely. I have that conversation a lot with patients because they’ll go online, they’re like, “I got this treatment.” Then they see all of the oncology reports and get terrified because of everything that comes up with those. Oftentimes the good thing is the doses we use are much lower. They’re not meant to do the whole full-blown oncology mechanism side of it. I reassure them with that, these are much lower doses. The trials we’ve had have had different adverse effect profiles. You look those up, it has the oncology adverse effects and then it has the MS adverse effects. It also means we have more time to look and see how patients with exposure to those medications do. Because I remember in other disease states, when we have novel mechanisms come out, I’m constantly telling patients, this is what we saw in the trials, but we don’t know about in the real world yet. Being able to take these therapies that have been used a lot in other disease states helps give us that foundation.

Ryan Haumschild, PharmD, MS, MBA: Excellent. Thank you for that. From a payer perspective, I’m always curious, because there are so many agents. Dana, when we think about it, in the last 30 years, there have been numerous disease-modifying therapies that have become accessible for treating MS. But there are newer agents on the horizon, and specifically, BTKis. My question to you is, what are some of those BTK inhibitors in the pipeline that are being studied in patients with MS?

Dana McCormick, RPh: Dr Hickman, the concept of having medications that are already out in use, and being able to take that experience and extrapolate it, will make this very important for BTKi research that’s being done in MS, and the ability for that to be taken up quicker probably than if it was just a totally novel mechanism of action, so that’s super positive.

There are 5 BTKis that are being studied in various clinical trial phases specifically for the treatment of relapsing-remitting MS. They’re all double placebo-controlled trials. Some of them also are using teriflunomide as a comparator, and there’s one that is using ocrelizumab as a comparator as well. These are some studies that are going to be bringing safety and efficacy but also some comparative effectiveness as well, which we always like to have as we think about improvements in the treatment landscape and how we’re going to position new products when they come to the market. Remibrutinib, fenebrutinib, and orelabrutinib are 3 of the agents being studied. They’re all in phase 2 and phase 3 trials, and probably expected to come to market, assuming everything progresses efficiently, later. But we are expecting in 2024 some data to come out around evobrutinib and tolebrutinib. Those studies are fully enrolled, active, and ongoing, and we hope to have some data reported in 2024 and be able to have some treatment improvements.

Ryan Haumschild, PharmD, MS, MBA: It’s an exciting landscape, especially when you look at the pipeline. That’s something I think we’re always trying to look forward to.

Dana McCormick, RPh: I know. If you think about too all the current BTKis that are used for other indications, there’s a high likelihood those will be considered and studied for MS as well.

Mitzi Joi Williams, MD FAAN: I think the other thing that’s exciting is having classes of drugs with MS. Because for a very long time, we only had 1 [class of] drug, we had interferons. There were interferons, and then there was everything else. Everything else was 1 medicine, that 1 agent, with 1 mechanism of action, and you had to try to explain how this was different from this, and why you needed this. I also think it’s very exciting that we now have classes of therapies with multiple options, which again could potentially lead to increased accessibility. If we have multiple agents, we hopefully can get at least 1 option within that class of drugs to be able to offer our patients regularly.

Transcript edited for clarity.

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