The U.S. Food and Drug Administration (FDA) has approved inebilizumab-cdon (Uplizna; Amgen) for the treatment of adults with generalized myasthenia gravis who are anti-acetylcholine receptor and anti-muscle-specific tyrosine kinase antibody-positive. As the FDA approves inebilizumab-cdon, the decision introduces a new targeted option for a rare, chronic autoimmune neuromuscular disorder. The approval covers a dosing regimen of two initial loading infusions followed by one maintenance dose every six months. Inebilizumab-cdon for generalized myasthenia gravis selectively targets CD19-positive B cells, including plasmablasts and certain plasma cells involved in autoantibody production, supporting sustained disease control with reduced treatment frequency.
Following the initial dosing phase, patients receive inebilizumab-cdon twice yearly, a schedule designed to simplify long-term management for individuals who may find frequent or complex regimens difficult to maintain. In addition to its newly approved indication for generalized myasthenia gravis, the therapy is also approved for adult patients with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder and immunoglobulin G4-related disease. Commenting on the decision, Jay Bradner, MD, executive vice president of research and development at Amgen, said in a news release, “This approval marks a significant advancement for people living with gMG. By selectively targeting CD19-positive B cells, [inebilizumab] offers a new approach to treatment that addresses a biological root cause of disease. [Inebilizumab] is conveniently dosed twice a year and delivers durable efficacy, helping people manage debilitating symptoms that can compromise daily function—including trouble breathing, speaking, and seeing.”
The FDA decision on inebilizumab-cdon for generalized myasthenia gravis was supported by findings from MINT (NCT04524273), a randomized, double-blind, placebo-controlled, parallel-group phase 3 trial evaluating efficacy and safety in adults with gMG. The study enrolled 238 patients, including 190 who were AChR-positive and 48 who were MuSK-positive. Participants were randomized to receive intravenous inebilizumab at a dose of 300 mg on days 1 and 15, with an additional dose on day 183 for AChR-positive patients, or a matching placebo. Treatment continued for 52 weeks in AChR-positive participants and 26 weeks in MuSK-positive participants. The primary endpoint assessed change from baseline in the Myasthenia Gravis Activities of Daily Living score at week 26, while a key secondary endpoint measured change in the Quantitative Myasthenia Gravis score over the same period.
Results from the trial showed that patients treated with inebilizumab achieved greater reductions in disease activity than those receiving placebo, supporting the decision as the FDA approves inebilizumab-cdon for generalized myasthenia gravis. Least-squares mean changes in MG-ADL scores were –4.2 with inebilizumab compared with –2.2 for placebo, while QMG scores declined by –4.8 versus –2.3, respectively. Richard J. Nowak, MD, MS, global principal investigator and director of the Myasthenia Gravis Clinic at Yale University, said in the news release, “[Inebilizumab] showed strong efficacy at 26 weeks in both AChR-positive and MuSK+ patients, with AChR+ patients continuing to improve through 52 weeks in MINT.” The most commonly reported adverse events included headache, cough, nasopharyngitis, infusion-related reactions, and urinary tract infections, with no higher incidence of serious adverse events observed. Manufacturers noted the potential risk of infections and possible fetal harm. Responding to the approval, Samantha Masterson, president and CEO of the Myasthenia Gravis Foundation of America, said the therapy offers durable efficacy and extended treatment-free intervals for people living with gMG.
