James Stankiewicz, MD: The State of Multiple Sclerosis Treatment

APRIL 14, 2018
Matt Hoffman
James Stankiewicz, MD, an assistant professor of neurology at Harvard Medical School and the clinical director of the Partners MS Center sat with MD Magazine to discuss the therapies he's keeping an eye on in multiple sclerosis pipeline, as well as the biggest advancement in MS treatments in the last decade, the biggest unmet needs for patients, and the challenges that physicians treating MS must overcome in order to provide the best care.

James Stankiewicz, MD:
I think that the landscape is continually evolving. In the short-term, the 2 kind of more interesting things will be cladribine, which I think probably will get FDA approval. It has an interesting mechanism, so that patients get an oral pill just for like 5 days or so and then it carries them over for a year, then they would get reduced. In general, I'd say that the efficacy of the drug is pretty good, and the safety profile looks pretty good, so I think that it'll be a good option for some patients.

Another one that I think might be interesting for some patients is siponimod, which is a retooled sphingosine receptor drug, and yet it was trialed in a secondary progressive patient population and had some effect. So, I think for some secondary progressive patients who really don't have a lot of options, that might be something that some find attractive.

I think another drug—another two drugs—that are kind of interesting anti-LINGO [opicinumab] is being trialed again in a updated phase 2 trial with more careful selection criteria and so that's something that may show some effect, and over the long term I think will be appealing to patients because it may offer the ability to repair damage that's already been done to a certain extent. So, I think that that will be exciting for people. Then the last one will be like ofatumumab, which is similar to ocrelizumab, but is a fully humanized monoclonal antibody that works on b-cells, and I think maybe a little bit easier in the sense that it's an injection rather than an IV.

I think the biggest thing for me is ocrelizumab. I think was a real game changer because it's got a great efficacy and the side-effect profile, as we know it to this point, I would describe as relatively benign. The length of administration—so that patients could take it and [be] protected for 6 months—I think that gives patients a lot of liberty, and the combination of those things makes this a very good drug for MS patients, for many MS patients I should say. I think that we didn't have that option before for patients, so that's been a really nice introduction that's at least, for me, changed how we think about relapsing remitting disease.

It was a proof of concept, there was a trial with rituximab before that showed that by depleting b-cells you can have a strong effect on attenuating MS, and so we expected that this would happen with ocrelizumab as well, but we had a large-scale phase 3 trials that we didn't have with rituximab. But when the rituximab early phase 2 data came out, it was kind of a proof of concept that b-cells are involved in the disease and depleting b-cells actually can help treat the disease.

Prior to that, I think we really were more heavily focused on T cells as being heavily involved in the pathogenesis of MS, and the b-cells were playing a lesser role. I think because we're able to have a nice effect on the disease with the b-cell depletion, it tells us that it's probably important.

I think there are 2 things. I think we need treatments for progressive MS—we have some treatments that have been approved, for example ocrelizumab has been approved for primary progressive MS and siponimod probably will likely be approved for a second progressive MS, but at the end of the day, the effects on the disease and those patients I would describe as somewhat weak.

I think we need better treatments for progressive disease and, in fact, I think we just need simply a better understanding of progressive disease and what's happening—what is the pathophysiology? We have some ideas, but I don't know that we have any sort of definitely defined framework.

Then, I think the other big need is just to understand in early relapsing disease, is it better if we use stronger drugs earlier or if it doesn't really matter, it's more just that people get on treatment more immediately. I have my own theories, but I think, ultimately, there are people that are putting together trials that will know that results of it. That will take us 4 years, but I think those will be important.

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