EAN 2026 | Tolebrutinib and disability by MRI activity: post-hoc analysis of HERCULES and GEMINI
Anthony Traboulsee, MD, University of British Columbia, Vancouver, Canada, discusses a post-hoc analysis of the Phase III HERCULES (NCT04411641) and GEMINI (NCT04410978; NCT04410991) trials exploring the effect of tolebrutinib on disability in relation to MRI activity. Prof. Traboulsee shares findings suggesting that tolebrutinib targets the mechanisms underlying disability progression, independently of those driving relapses. This interview took place at the 12th Congress of the European Academy of Neurology (EAN) in Geneva, Switzerland.
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Transcript
We’ve been involved with the BTK inhibitors. These are new drugs that are targeting progressive multiple sclerosis. The idea is that they’re small molecules that can penetrate into the central nervous system and work on the mechanisms of progressive MS called microglia. Part of the big HERCULES study and the GEMINI studies for tolibrutinib, one of the BTK inhibitors, was to determine if there’s still ongoing focal inflammatory activity, as defined by MRI activity, does that decrease the effectiveness of the drug in preventing progression? And through this post-hoc analysis, we divided patients into those that had ongoing MRI activity, which was a small percentage, and those that had no MRI activity during the study, and we found no difference in the effect of the drug on suppressing or preventing disability progression...
We’ve been involved with the BTK inhibitors. These are new drugs that are targeting progressive multiple sclerosis. The idea is that they’re small molecules that can penetrate into the central nervous system and work on the mechanisms of progressive MS called microglia. Part of the big HERCULES study and the GEMINI studies for tolibrutinib, one of the BTK inhibitors, was to determine if there’s still ongoing focal inflammatory activity, as defined by MRI activity, does that decrease the effectiveness of the drug in preventing progression? And through this post-hoc analysis, we divided patients into those that had ongoing MRI activity, which was a small percentage, and those that had no MRI activity during the study, and we found no difference in the effect of the drug on suppressing or preventing disability progression. So that was really encouraging to suggest that we are targeting the mechanism of progression that seemed to be independent of the mechanisms of relapses and focal inflammation.
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