Rosnilimab: A New Era of Upstream RA Disease Control, With Jonathan Graf, MD

Rosnilimab, a potential first-in-class novel monoclonal antibody targeting pathogenic T-cells, has emerged as one of the most promising investigational therapies in rheumatoid arthritis (RA) in over a decade.

Findings from a phase 2b, multicenter, randomized, double-blind, placebo-controlled trial (NCT06041269) evaluating the therapy were presented by Jonathan Graf, MD, Professor of Medicine at the University of California, San Francisco, at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois.

The trial enrolled 424 adults with moderate to severe seropositive RA who were on background conventional synthetic DMARDs and had received fewer than 3 prior biologic or targeted synthetic DMARDs. Participants were randomized to receive subcutaneous rosnilimab at varying doses (100 mg or 400 mg every 4 weeks, or 600 mg every 2 weeks) or placebo. At week 12, all rosnilimab arms met the primary endpoint, demonstrating significantly greater mean reductions in DAS28-CRP compared with placebo (–2.06 to –2.12 vs –1.69; P < .01). Improvements were also observed across ACR20/50/70, CDAI low disease activity, and multiple patient-reported outcomes, with responses sustained through 28 weeks and maintained off drug through week 38.

Rosnilimab acts by selectively binding to PD-1–high T peripheral helper (Tph) and T follicular helper (Tfh) cells—pathogenic subsets that drive B-cell activation, autoantibody production, and chronic inflammation—while preserving overall T-cell function. Translational data revealed >90% depletion of these disease-driving T cells in both blood and synovial tissue, accompanied by broad downregulation of T-cell, B-cell, and myeloid gene activation signatures.

HCPLive spoke with Graf to learn more about rosnilimab's potential to disrupt the RA treatment landscape with its novel mechanism which acts upstream of many established inflammatory pathways.

"There's been a relative lack of clinical development in the RA space and I believe there hasn't been, if you exclude surgical, implantable procedures, a novel therapeutic class developed for RA in over a decade. For a disease that's so prevalent in rheumatology... it's conspicuous that there hasn't been significant development," Graf said. "Rosnilimab really represents the first of a novel class of drugs that's really, I think, going to make a lot of headlines in the future for treating RA."

Graf's disclosures include Amgen, AnaptysBio, Fate Therapeutics, ImmPACT Bio, and Sonoma Biotherapeutics.

Reference

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. resented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Abstract #LB19