Remibrutinib Exposure in Cerebrospinal Fluid: Insights from a Study in Healthy Participants
Gilbert Lefèvre1, Xianbin Tian1, Somesh Choudhury1, Roman Willi2, Bernd Kieseier2, Lyric Yang Liu1, Robert Beecham1, Stefan Viktor Vormfelde1, Hanns-Christian Tillmann1
1Novartis Biomedical Research, Translational Medicine, Basel, Switzerland, 2Novartis Pharma AG, Basel, Switzerland
Objective:
To investigate the exposure of remibrutinib in cerebrospinal fluid (CSF) in healthy participants.
Background:
Remibrutinib is a highly selective and potent, covalent, oral Bruton’s tyrosine kinase inhibitor that downregulates myeloid and B-cell activation without cellular depletion. Two pivotal phase 3 trials, REMODEL-1 (NCT05147220) and REMODEL-2 (NCT05156281), are ongoing to assess the therapeutic potential of remibrutinib as a novel treatment for patients with relapsing multiple sclerosis (MS). Preclinical studies indicated the exposure of remibrutinib in the CSF and brain. This is the first study to assess CSF exposure to remibrutinib in humans.
Design/Methods:
Remibrutinib exposure in CSF was assessed in a phase 1, participant-blinded, randomized, placebo-controlled study. Healthy men and women weighing at least 50 kg, aged between 18 and 55 years (inclusive), were included in the study. A total of 16 healthy participants were randomized to receive either remibrutinib (n=12) or placebo (n=4). Participants received either remibrutinib (100 mg twice daily) or placebo on days 1 and 2 (12 hours apart), and remibrutinib (100 mg, single morning dose only) or placebo on day 3. One CSF sample per participant was collected either at 0.5, 1 or 2 hours to determine remibrutinib concentration in CSF. Blood samples were also collected at designated timepoints over 48 hours post-dose on day 3.
Results:
Remibrutinib was successfully measured in the CSF of all participants in the remibrutinib group at all timepoints, whereas it was not detected in any CSF samples from participants who received placebo.
Conclusions:
The distribution of remibrutinib into the CSF may imply that remibrutinib may exert pharmacotherapeutic effects in the central nervous system, potentially benefiting conditions such as MS.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.