Novel B-Cell Therapy Shows Sustained Benefits in gMG

A first-in-class therapy targeting two key regulators of B-cell activity showed robust and sustained benefits in patients with generalized myasthenia gravis (gMG), with clinical responses deepening over 48 weeks.Results of a post hoc analysis of the phase 3 trial showed that telitacicept produced sustained improvements in disease severity and daily functioning over 48 weeks, with approximately 42% of patients achieving minimal symptom expression (MSE) and most maintaining that response over time.The analysis examined the depth and durability of response to telitacicept over 48 weeks, including the proportion of patients achieving meaningful improvements in daily functioning and MSE.This new analysis provides important insights, study investigator Richard J. Nowak, MD, MS, associate professor of neurology, Yale School of Medicine, and director of the Yale Myasthenia Gravis Clinic, New Haven, Connecticut, told Medscape Medical News.“At the end of the day, I think the important information here is that there’s a durability of response,” said Nowak. “Not only did patients get better in the initial study period, but they continued to remain better, and maybe improve further, the longer they were on the medication.”The study was presented on September 29 at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2026.Telitacicept is a fusion protein that inhibits B-cell activating factor and a proliferation-inducing ligand — key cytokines involved in B-cell survival, differentiation, and antibody production.In regulating early pathogenic B-cell responses, the agent may provide broader immune control compared with therapies targeting downstream signaling pathways. The medication is administered weekly as a self-administered subcutaneous injection.The multicenter phase 3 trial included 114 adults with gMG who were positive for acetylcholine receptor (AChR) antibodies or muscle-specific kinase antibodies, had Myasthenia Gravis Foundation of America (MGFA) class II-IVa disease, and had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 6. Participants were randomly assigned to receive telitacicept 240 mg once weekly or placebo.The results of the original study showed the mean change from baseline in the MG-ADL score was -5.74 in the telitacecept group compared to -0.91 in the placebo group (P < .001) at 24 weeks. Results that led to the drugs approval for gMG in China.Following the initial 24-week randomized phase, participants entered a 24-week open-label extension in which all received telitacicept. The post hoc analysis examined whether clinical responses deepened and remained durable over time, assessing the magnitude of patient- and physician-reported improvements, achievement of MSE, and maintenance of clinical benefit.The analysis included 57 participants in each of the treatment and control groups. They had a mean of age 49 years, with a greater percentage of men in the treatment group (52.6% vs 36.8%). Two thirds of patients had moderate-to-severe disease. Mean baseline MG-ADL scores were similar at 10.0 in the treatment group and 9.9 in the placebo group.Depth and DurabilityAt week 24, almost all participants (98%) in the active group had at least a 3-point improvement in MG-ADL responses compared to 12% in the placebo group.This treatment benefit persisted at week 48, with 96.2% in the original treatment group and 90.2% in the crossover group achieving the 3-point reduction.“It seems like there might be a greater depth of response the longer the participant is on the drug,” said Nowak.Researchers plotted MSE over time on a Kaplan-Meier graph. At 24 weeks, the estimated probability of achieving MSE was 23.7% in the treatment group vs 3.6% in the placebo group. By 48 weeks, this had increased to 42.6% among those treated continuously and 40.7% among those who crossed over from placebo.MSE is an important treatment goal for many patients, Nowak said, because they want to know how likely they are to become nearly symptom-free and how long it might take to reach that point.More than half (51.7%) of participants with baseline MG-ADL score of 6-8 and 20.5% of those with baseline MG-ADL score of 9-10 achieved MSE at 48 weeks.Telitacicept was generally well tolerated with no new safety signals at 48-week follow-up. In those receiving at least one dose, 87.3% had a treatment-related adverse event and 10.0% experienced a serious adverse event. Upper respiratory tract infections occurred in 29.1%, and urinary tract infections in 16.4%.A global phase 3 trial has been launched to determine whether a more heterogeneous population with MG will also benefit from the intervention. The trial is fully enrolled, with topline results expected in the first half of 2027, Nowak said.Asked to comment on the findings, Nicholas S. Streicher, MD, assistant professor of neurology, Georgetown University, Washington, DC, said “the data look good”.However, as with other emerging MG therapies, questions remain about how best to integrate the drug into clinical practice. “While the data might look wonderful, the question is, where does it fit into clinical treatment?” Streicher said.Physicians are struggling to keep pace with the rapidly evolving MG treatment landscape and determine where each therapy fits, Streicher noted. Another key question is whether to initiate aggressive treatment early or follow the traditional, more gradual stepwise approach, he added.Nowak reported receiving research support from Alexion Pharmaceuticals; Alira Health; Annexon Biosciences; Argenz; Genentech; Grifols; Immunovant, Inc.; Momenta Pharmaceuticals, Inc. (now Janssen); MGFA; National Institutes of Health (NIH); Ra Pharmaceuticals, Inc. (now UCB); and Viela Bio (Horizon Therapeutics, now Amgen, Inc.). He reported also serving as a consultant and advisor for Alexion Pharmaceucals; Argenx; Caballeta Bio; Cour Pharmaceuticals; Immunovant, Inc; Momenta Pharmaceuticals, Inc. (now Janssen); Ra Pharmaceuticals, Inc. (now UCB); Viela Bio (Horizon Therapeutics, now Amgen, Inc.); and Vor Biopharma Inc.Streicher reported serving a site investigator for PREVAIL(a trial of the novel dual-binding nanobody gefurulimab in patients with anti-AChR antibody-positive gMG). He had a research relationship with Alexion, AstraZeneca Rare Disease, which develops gefurulimab. He reported serving a paid speaker and consultant for Amgen and an internal speaker consultant for Immunovant; Amgen, Inc.; and AstraZeneca.