Educational content on VJNeurology is intended for healthcare professionals only. By visiting this website and accessing this information you confirm that you are a healthcare professional.

Share this video  

ACTRIMS 2022 | Long-term safety and efficacy of tolebrutinib for relapsing multiple sclerosis

Jiwon Oh, MD, PhD, St. Michael’s Hospital, University of Toronto, Toronto, Canada, discusses BTK inhibitors (BTKi). BTKi can modulate B-cells, which are known to play a major role in MS pathophysiology. BTKi can also access the central nervous system (CNS) and modulate the innate immune system, including macrophages and microglia, which may contribute to disease progression independent of relapse. A current study is investigating one such BTKi, tolebrutinib, which has shown evidence of CNS penetration. A Phase IIb (NCT03889639) trial reported tolebrutinib was well tolerated over 12 weeks. A long-term extension study (NCT03996291) is now ongoing for those who completed the Phase IIb trial. By 18-months, the efficacy of tolebrutinib was sustained according to MRI and clinical measures, few patients had relapsed, and EDSS scores remained stable. No new safety signals have emerged. This interview took place at the ACTRIMS Forum 2022 in West Palm Beach, Florida.

Transcript (edited for clarity)

You’ve probably heard a lot about BTK inhibitors. It’s a compound of high interest in the MS field because we know that BTK inhibitors modulate B-cells, which we know play a major role in MS pathophysiology, but many of these BTK inhibitors likely also are able to get into the central nervous system and modulate the innate immune system, including macrophages and microglia. And we’re really focused on this right now because we think that’s the underlying mechanism of progression independent of relapses...

You’ve probably heard a lot about BTK inhibitors. It’s a compound of high interest in the MS field because we know that BTK inhibitors modulate B-cells, which we know play a major role in MS pathophysiology, but many of these BTK inhibitors likely also are able to get into the central nervous system and modulate the innate immune system, including macrophages and microglia. And we’re really focused on this right now because we think that’s the underlying mechanism of progression independent of relapses. And so this study that we reported on is looking at one of the BTK inhibitors known as tolebrutinib.

Tolebrutinib is one of the BTK inhibitors that has clear evidence of penetration into the central nervous system. And this study specifically is reporting the 18-month long-term extension of the Phase II clinical trial. So the Phase II clinical trial of tolebrutinib has already been published, but over a 16-week period there was clear efficacy of tolebrutinib at 60 milligrams on MRI measures, so GAD lesions, as well as T2 lesions. And this is a study that’s just following that Phase II trial out up to the 18-month point. And so bottom line is the results are reassuring because the efficacy that was seen on the MRI measures, as well as the clinical measures, which the study was not powered to look at but still, the efficacy that was seen in the original Phase II trial on the MRI measures was sustained for the most part. And with relapses and EDSS, there were very few patients who had a relapse during the 18-month extension and EDSS scores remained stable. And then also reassuringly, obviously we look at safety, and there were no additional new safety signals that emerged.

So overall good information because this is a new class of molecule. And it seems that based on Phase II trials there is efficacy, but we want to ensure that the safety piece is met. And obviously we’ll need more long-term follow-up, but for now the results are quite reassuring.

Read more...