During a recent PW Podcast episode, we spoke with Anthony Traboulsee, MD, Professor and Research Chair of the Multiple Sclerosis Society of Canada at the University of British Columbia in Vancouver, about phase II trial results he presented at the 2021 American Academy of Neurology annual meeting on tolebrutinib, an emerging new treatment for MS. Following is a summary of that interview:

What should neurologists know about the tolebrutinib phase II study results?

Tolebrutinib is a Bruton’s tyrosine kinase in- hibitor, a medication class used for lymphoma that affects B-cell function without depleting lymphocytes, thereby controlling the immune system without creating a risk for opportunistic infections. With many oral and infusion medica- tions for treating MS that are more convenient, better tolerated, and more effective than their predecessors, it wasn’t clear if there was room for another MS medication.

However, 130 patients entered the phase II trial for tolebrutinib, and only one dropped out, for a reason other than tolerability. Well-tolerated, safe medications that don’t deplete the immune system allow for transition between drugs more conveniently and safely. With the phase II trial, we used MRI measurement of inflammation as a simple outcome in patients with relapsing MS. Overall, tolebrutinib was very effective at pre- venting new MRI lesions, fitting into the highly effective class of medications, so far; that needs to be confirmed in phase III.

Looking at the subgroup of patients with highly active disease (relapse in the past year or an active-looking MRI with enhancing lesions), we found that the drug was just as effective as it was in the generally population of the study. It’s encouraging to know that it is a poten- tial broad-spectrum medication for very active MS, as well as average MS. It also works quite quickly. This study reached its outcome in 3 months following drug exposure.

What will the phase III trial look like? All currently available drugs for MS treatment mostly wok in the bloodstream, preventing ab- normal immune cells from crossing into the brain and causing damage. We think that part of the problem with progression is the presence of abnormal immune cells that reside in the brain, where these drugs can’t get to them. Some BTK inhibitors, especially tolebrutinib, have good penetration into the central nervous system. So, we hope to show in the phase III trial that tolebrutinib working in both the bloodstream and central nervous system will provide a dual mechanism of action that might not only prevent relapses but also stop progression, which would be a huge breakthrough in the MS world.

It’s really a time of hope in this area. About 20 years ago, we had very modest medications, and the thinking was, “This is just buying time un- til we get something better.” Well, now we have better medications for relapsing forms of MS, and I think we’re at the threshold of finding bet- ter medications for progressive MS. The future for MS treatment, I think, is very optimistic.

To listen to our full PW Podcast interview with Dr. Traboulsee, visit www.physiciansweekly.com/traboulsee or scan the QR code above.