Inebilizumab-cdon (Uplizna®) may reduce attack risk and disability in patients with neuromyelitis optica spectrum disorder (NMOSD) who typically have poor treatment response, according to phase 3 pivotal trial data recently presented at the Consortium of Multiple Sclerosis Centers Annual Meeting.

Most patients with NMOSD, a neuroinflammatory autoimmune disease, test positive for anti-aquaporin-4 (AQP4) antibodies, with B-cell populations being central to the pathogenesis of the disease. Treatment often includes monoclonal antibodies that bind to and reduce the B cells that drive disease activity.

However, immune system genetic variations can influence the efficacy of treatment. In particular, a “polymorphism in a gene that encodes the low-affinity Fc gamma receptor IIIa (FCGR3A) has been shown to reduce the effectiveness” of certain monoclonal antibodies in NMOSD, according to a news release from the drugmaker, Horizon Therapeutics plc.


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Inebilizumab-cdon “is a highly specific CD19 B-cell depleting agent that targets an extended range of B cells,” according to Horizon, and was purposely designed to bind strongly to FCGR3A to improve its efficacy in NMOSD patients regardless of FCGR3A genotype.

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As part of the pivotal N-MOmentum trial (NCT02200770), researchers evaluated the potential design advantage of inebilizumab-cdon in 142 patients who underwent genotyping to identify the FCGR3A genotype. “No significant differences in disease attacks or disability” were noted in patients with NMOSD, regardless of FCGR3A genotype, indicating the effectiveness of inebilizumab-cdon across patient genotypes, Horizon said in the news release.

“These data illustrate how mechanistic precision in treatment design can help patients gain benefit from their regimen regardless of the genetic make-up of their immune systems,” said Bruce Cree, MD, PhD, MAS, study author and professor of clinical neurology at the University of California San Francisco Weill Institute for Neurosciences.

Reference

Analysis from the phase 3 N-MOmentum study demonstrates the effectiveness of UPLIZNA® (inebilizumab-cdon) among neuromyelitis optica spectrum disorder patients with genetic variations. News release. Horizon Therapeutics plc; May 31, 2022.