Rosnilimab Shows Promise as Next-Generation Rheumatoid Arthritis Therapy in Phase 2b Trial

A novel T cell-depleting therapy, rosnilimab, has demonstrated significant potential in treating moderate-to-severe rheumatoid arthritis (RA), according to recent Phase 2b clinical trial results. Developed by AnaptysBio, the investigational drug showcased rapid symptomatic improvement and a favorable safety profile, potentially offering a new treatment option for RA patients who have not found relief with existing therapies.

Impressive Efficacy and Durability of Response

The global Phase 2b trial enrolled 424 patients with moderate-to-severe RA, evaluating three dosing regimens of rosnilimab against placebo. All three doses achieved statistically significant reductions in disease activity score (DAS-28 CRP) and ACR20 response at Week 12 compared to placebo.

Notably, 69% of patients across all rosnilimab doses achieved low disease activity (LDA) by Week 14, as measured by the Clinical Disease Activity Index (CDAI). The drug's efficacy appeared comparable to JAK inhibitors, with deepening responses on CDAI LDA, CDAI remission, and ACR70 observed at six months.

Dr. Jonathan Graf, professor of Medicine at the University of California, San Francisco, and trial investigator, remarked, "Witnessing rosnilimab, with its novel mode of action, dramatically reduce RA disease activity through six months in most patients, whether having failed biologic or targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) therapies or b/tsDMARD-naïve, is truly exciting for patients living with this disease and the field of RA treatment."

Novel Mechanism of Action Targets Pathogenic T Cells

Rosnilimab's unique approach involves selectively depleting pathogenic T cells while maintaining regulatory T cells (Tregs). In RA patients, over 80% of T cells in joint tissue are pathogenic, and their peripheral blood contains twice as many pathogenic T cells as non-RA patients.

Research indicates that rosnilimab depletes more than 90% of pathogenic T cells in both the periphery and synovium. This level of depletion surpasses that of other T cell-targeting therapies in development, such as Lilly's peresolimab and JNJ's JNJ-67484703, which only deplete approximately 50-60% of pathogenic T cells in the periphery.

Dr. Graf added, "Impressive translational data provide further evidence that by targeting specific pathogenic T cells, rosnilimab has a substantial impact downstream on multiple known pathways that drive RA pathogenesis, with the potential to restore immune homeostasis necessary to achieve meaningful, long-lasting disease remission."

Safety Profile and Future Prospects

Consistent with previous studies, rosnilimab demonstrated a favorable safety and tolerability profile across all doses in the Phase 2b trial. There were no treatment-related serious adverse events, malignancies, anaphylaxis, or systemic hypersensitivity reported. The incidence of injection site reactions and serious infections was low and balanced relative to placebo.

The durability of response observed in the trial, with patients maintaining LDA for at least three months after discontinuing treatment, suggests the potential for extended dosing intervals in future clinical trials. This could offer a significant advantage for patients in terms of convenience and potentially reduced side effects.

As the first new class of RA medicine to show promise since 2012, rosnilimab represents a potential breakthrough in a market valued at over $20 billion in the United States alone. With up to a quarter of RA patients unable to find symptom relief with current therapies, the development of rosnilimab could address a significant unmet need in the treatment of this chronic autoimmune disease.