Use of High-Efficacy Therapies for Treatment of Relapsing Multiple Sclerosis - Episode 7

Evobrutinib in MS: The EVOLUTION RMS I and II Trials

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Thought leaders in neurology consider the role of BTK inhibitors such as evobrutinib and review the potential impact on patients with progressive multiple sclerosis.

Enrique Alvarez, MD, PhD: As we start looking at new therapeutic areas, we’re starting to see the last S1P drug that we’re expecting, with ponesimod also being recently approved. Ublituximab is the last of the B-cell therapies in the MS [multiple sclerosis] realm that will likely come out into this group, at least for now. We can start looking at new drug classes.

The BTK inhibitors are becoming really interesting. Almost all the drug companies that are involved in the MS space have their own BTK [Bruton tyrosine kinase] inhibitor. We’re starting to see some data for evobrutinib that look promising. We’re starting to see trials being developed for tolebrutinib by Sanofi and for fenebrutinib by Roche/Genentech. There are discussions of Biogen and Novartis also having BTK inhibitors. Even TG Therapeutics, which has ublituximab, has a BTK inhibitor. Deciding among these therapies will be important. Seeing how the data look for these therapies becomes really exciting.

These are small-molecule drugs that can theoretically penetrate at least into the brain. There are some data for all these medicines indicating that is the case. That gives us a chance to potentially get into the immune system cells that are already in the central nervous system. That might be especially important for progressive disease, so seeing that some of these trials are starting to include arms for progressive patients is really exciting. We’ll see if that’s true. It will start allowing us to test our hypothesis that those cells might be important and give us more tools for the treatment of progressive disease.

We’ve had a rough year or 2, as far as treatments for progressive disease. There have been treatments that have not borne out and showed good results, and their development has been halted. Because of this, the idea of having new drug classes in this group is important. There are a lot of other therapies that are still being tried in the phase 1 and 2 trials. That is interesting as well. In 2 to 4 years, we’ll potentially start seeing a lot of new classes being developed for MS.

Lawrence Steinman, MD: Targeting the BTK pathway is very promising. We’ll see what the results look like after the phase 3 trial, but there’s always progress in the field. Some of the bigger unmet needs are in primary progressive MS. We’ll see whether these drugs are developed and what they look like compared with ocrelizumab, which is approved for primary progressive MS.

One of the biggest questions in multiple sclerosis is, could we ever have the perfect therapy? Could we ever talk about the word cure? We need to know a lot more about the disease, but 1 of our biggest impediments is going to be testing new and potentially effective drugs that may get us to the cure, given how good some of the current drugs are, particularly in the RRMS [relapsing/remitting multiple sclerosis] space. In a sense, we’ll be victims—in a very pleasant use of the word victim—of our own success, with success being how effective these various drugs and different oral and injectable categories are in stopping relapsing/remitting disease.

Transcript Edited for Clarity