Evobrutinib Acts as Immunomodulator, Inhibiting Aberrant Immune Cell Responses

Strategic Insights -

Research findings on the Coronavirus - COVID-19 have shown that evobrutinib, an investigational drug for patients with relapsing multiple sclerosis, acts as an immunomodulator, maintaining responsiveness to foreign de novo and recall antigens. A post hoc analysis of patients with relapsing multiple sclerosis who received evobrutinib and SARS-CoV-2 vaccines during the open-label extension showed that the majority of patients had a 10-100-fold increase in antibody levels pre- to post-vaccination. The study concluded that evobrutinib inhibits aberrant immune cell responses in patients with relapsing multiple sclerosis, while maintaining responsiveness to vaccines.

Key Takeaways:

  • Evobrutinib is an oral, central nervous system (CNS)-penetrant and highly selective covalent Bruton's tyrosine kinase inhibitor under clinical development for patients with relapsing multiple sclerosis (RMS).
  • A post hoc analysis of patients with RMS who received evobrutinib 75 mg twice daily and SARS-CoV-2 vaccines during the open-label extension (n = 45) was conducted, and 43 of 45 patients developed/increased S1/S2 IgG antibody levels post-vaccination.
  • Most patients (n = 36/45), regardless of pre-vaccination serostatus, had a 10-100-fold increase of antibody levels pre- to post-vaccination.
  • Antibody levels post-booster were higher versus post-vaccination.
  • The study was conducted at the University of Pennsylvania, and financial support for the research came from Merck Healthcare KGaA, Darmstadt, Germany.
  • Amit Bar-Or, from the University of Pennsylvania, Perelman School of Medicine, Ctr Neuroinflammat & Expt Therapeut, Dept. of Neurology, was a researcher on the study.
  • Additional authors included Anne H. Cross, Anthony L. Cunningham, Yann Hyvert, Andrea Seitzinger, Hans Guehring, Nektaria Alexandri, Elise E. Drouin, Davorka Tomic, and Xavier Montalban.

Statistics:

  • 43 of 45 patients developed/increased S1/S2 IgG antibody levels post-vaccination.
  • 36/45 patients had a 10-100-fold increase of antibody levels pre- to post-vaccination.
  • Mean/minimum evobrutinib exposure pre-vaccination was 105.2/88.7 weeks.
  • Total number of patients who received evobrutinib and SARS-CoV-2 vaccines during the open-label extension was 45.

Sources:

  • NewsRx. New COVID-19 Findings from University of Pennsylvania Described (Antibody Response To Sars-cov-2 Vaccines In Patients With Relapsing Multiple Sclerosis Treated With Evobrutinib: a Bruton's Tyrosine Kinase Inhibitor). Medical Letter on the CDC & FDA. October 22, 2023; p 220.
  • Antibody Response To Sars-cov-2 Vaccines In Patients With Relapsing Multiple Sclerosis Treated With Evobrutinib: a Bruton's Tyrosine Kinase Inhibitor. Multiple Sclerosis Journal, 2023.