U.S. Neurologists Eagerly Await Promising Oral BTKis in MS Treatment Pipeline, Though Recent Trial Readouts Might Hamper Initial Excitement

Stuart SchlossmanMS Drug Therapies, MS Research Study and Reports, Multiple Sclerosis

 Efficacy and safety of pipeline multiple sclerosis assets viewed as increasingly important characteristics, according to Spherix Global Insights. 


[Exton PA, December 13, 2023] — Several clinical trials are underway for Bruton’s tyrosine kinase inhibitors (BTKi) targeting relapsing and progressive multiple sclerosis (RMS/PPMS). These BTKi’s, administered orally, possess the advantage of easy dosing while leveraging their small molecular structure to effectively traverse the blood-brain barrier, providing both anti-inflammatory and neuroprotective advantages. Consequently, their convenient delivery and perceived therapeutic benefits have garnered positive attention among their future prescribers, and they were thought to present a potential alternative mechanism to infused monoclonal antibodies, currently established as the gold standard in RMS/PPMS treatment. 

As orally administered BTKi’s are already established in oncology, there was a notable level of awareness, familiarity, and anticipation surrounding these developmental assets amongst neurologists. Through Spherix’s quarterly RealTime Dynamix™ market tracker, neurologists and MS specialists have expressed an increasing level of enthusiasm for these investigational therapies over time. Impressively, more than one-third of surveyed neurologists spontaneously highlighted the development of BTKi’s as the most pivotal event on the MS horizon throughout 2023 surveys. Additionally, BTKi’s collectively stood out as the most readily recalled developmental assets among healthcare providers. This heightened interest extended to AB Sciences’ masitinib, a selective tyrosine kinase inhibitor.  

However, a sudden twist has unfolded with two BTKis, currently in or near completion of pivotal phase 3 trials for RMS, as they encountered setbacks involving safety and efficacy concerns. On November 30th, Roche/Genentech disclosed that the FDA had placed fenebrutinib on a partial clinical hold due to elevated liver enzymes observed in two patients. Shortly after, EMD Serono announced that evobrutinib failed to achieve its primary goal of reducing the annualized relapse rate compared to active comparator, oral teriflunomide in both Phase 3 studies. Amid substantial anticipation for these and other BTKis from Biogen (BIIB091), Novartis (remibrutinib), and Sanofi (tolebrutinib), these setbacks come at a pivotal juncture.  

In the latter half of 2023, Spherix tracking revealed a rising anticipation for the BTKi’s in development while neurologists concurrently emphasized a shift in priorities, placing increased emphasis on safety and efficacy while de-emphasizing the significance of dosing convenience. When specifically focusing on the BTKi’s, twice the number of neurologists emphasize their anticipated efficacy, rather than favorable safety, as the driver for prescribing this new mechanism of action once it enters the market.  

With the recent trial outcomes impacting two of the prominent BTKi’s in development, the optimistic prospects for this class now face uncertainty. This situation potentially paves the way for masitinib to emerge as a standout oral option in the landscape. Spherix will be assessing the implications of the recent fenebrutinib and evobrutinib updates on perceptions concerning these individual assets, the wider BTK class, and the entirety of the MS pipeline within their forthcoming RealTime Dynamix™ 2024 coverage. 

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