Novel pathogenic T cell-targeting monoclonal antibody yields durable responses in rheumatoid arthritis, study shows
Presenter: Paul Emery, MD, FRCP, MA, MBBCH, University of Leeds, Leeds, United Kingdom
Rosnilimab, a selective and potent depleter of pathogenic T cells, demonstrates efficacy, safety, and translational proof of mechanism in a rheumatoid arthritis phase 2B trial. Abstract LB19. Presented October 29, 2025.
Treatment with a novel monoclonal antibody that targets pathogenic T cells was well tolerated with promising efficacy in adult patients with moderate-to-severe rheumatoid arthritis, investigators reported at ACR Convergence 2025.
The investigational agent, rosnilimab, potently depleted pathogenic T cells of interest while producing clinically meaningful and durable responses, according to phase 2b trial results presented in a late-breaking oral abstract session at the meeting.
Altogether, these data support continued exploration of rosnilimab, said researcher Paul Emery, MD, FRCP, MA, MBBCH, of the University of Leeds in the United Kingdom.
“Based on these data and the unmet need in rheumatoid arthritis, where there's a large number of treatment-resistant patients, further clinical development of rosnilimab is warranted,” Dr. Emery said in his podium presentation.
The pathogenic T cells targeted by rosnilimab play a role in inflammation and are upstream of a wide range of validated clinical targets in rheumatoid arthritis, including tumor necrosis factor alpha, interleukin 6, and B cells, according to Dr. Emory.
As a selective and potent depleter of those pathogenic T cells, rosnilimab “has the potential advantage of restoring immune homeostasis,” he added.
The multicenter, randomized, double-blind, placebo-controlled, phase 2B trial of rosnilimab included 424 adults with moderate to severe rheumatoid arthritis. All were on concurrent conventional disease-modifying antirheumatic drugs.
By design, all the patients had previously received fewer than 3 biologic or targeted synthetic disease-modifying antirheumatic drugs. Overall, 41% had been exposed to these agents.
Patients were randomized to receive subcutaneously administered rosnilimab in one of three dosing regimens or placebo.
The primary endpoint, mean change from baseline in severity of rheumatoid arthritis by week 12 of the study, was met in all three rosnilimab dosing groups, Dr. Emory reported.
Changes in that efficacy endpoint, as measured using the Disease Activity Score 28 for Rheumatoid Arthritis with C-Reactive Protein (DAS 28-CRP), ranged from –2.06 to –2.12 for the three dosing groups, compared with –1.69 for placebo (P < .01 for all three comparisons to placebo).
Also at week 12, compared with the placebo group, significantly more patients in all rosnilimab dosing groups had achieved a 20% reduction in symptoms by the criteria of the American College of Rheumatology (ACR 20), and they had a greater mean reduction in C-reactive protein levels.
By week 14 of the study, 220 rosnilimab-treated patients (69%) met criteria for low disease activity. Those patients continued treatment until week 28 of the study, when treatment was stopped.
In those 220 patients continuing treatment, improvements in efficacy endpoints and patient-reported outcomes were observed at week 28, the time point when study treatment ended.
Clinical responses were sustained throughout the off-drug follow-up period, which lasted from week 28 through week 38, Dr. Emory said.
In laboratory data findings, rosnilimab rapidly eliminated more than 90% of the pathogenic T cells of interest driving rheumatoid arthritis inflammation, data show.
Treatment was well tolerated, Dr. Emory said, with no deaths or malignancies and no serious or severe infections resulting in treatment withdrawal in rosnilimab-treated patients.
Disclosures
Paul Emery, MD, FRCP, MA, MBBCH, reported disclosures (advisor or review panel member) related to Activa, AnaptysBio, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Immunovant, and Novartis.
References
Graf J, Archer A, Kovalenko S, et al. Rosnilimab, a selective and potent depleter of pathogenic T cells, demonstrates efficacy, safety, and translational proof of mechanism in a rheumatoid arthritis phase 2B trial [abstract]. Arthritis Rheumatol 2025; 77 (suppl 9). https://acrabstracts.org/abstract/rosnilimab-a-selective-and-potent-depleter-of-pathogenic-t-cells-demonstrates-efficacy-safety-and-translational-proof-of-mechanism-in-a-rheumatoid-arthritis-phase-2b-trial/. Accessed October 30, 2025.