Rosnilimab Demonstrates Historic Responses for Rheumatoid Arthritis

Jonathan Graf, MD,

Credit: University of California, San Francisco

Rosnilimab has demonstrated historic American College of Rheumatology (ACR) and clinical disease activity index (CDAI) low disease activity (LDA) responses in patients with rheumatoid arthritis (RA) in new findings from a phase 2b trial.¹

Rosnilimab is a depleter and agonist of PD-1+ T cells, for moderate-to-severe RA, and is being evaluated in the global 424-patient Phase 2b RENOIR trial for efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics in patients with moderate-to-severe RA on background conventional disease-modifying antirheumatic drugs (cDMARDs) such as methotrexate.²

“In RA, there is an urgent need for innovative therapies such as rosnilimab, which have the potential of reducing the debilitating effects of this disease for a longer period of time for a broader range of patients,” investigator Jonathan Graf, MD, professor of Medicine, Division of Rheumatology at the University of California, San Francisco, said in a statement.¹ “RA patients have an abnormal population of PD-1high expressing T cells circulating in their bloodstream and joints. I am strongly encouraged by these Phase 2 data, which support the hypothesis that by depleting these PD-1high expressing T cells and agonizing the remaining PD-1+ T cells, rosnilimab offers a fundamentally different approach to treating RA by resetting the immune system, potentially offering more durable relief of symptoms and disease modification.”

The new findings are from week 12 data from RENIOR. Participants had a mean baseline disease activity score -- 28 joints (DAS-28) C-Reactive Protein (CRP) score of 5.64 and mean baseline CDAI score of 37.7 across the United States, Canada and Europe. Participants had disease that was either biologic or targeted synthetic DMARD (b/tsDMARD) naïve (n=250; 59%) or experienced (n=174; 41%). Those who had prior use of b/tsDMARDs reported prior utilization of at least 1 biologic or targeted synthetic therapy, such as TNFα inhibitors, B cell inhibitors, selective costimulatory modulators or JAK inhibitors.¹

Participants were randomized to receive either 100mg of subcutaneous rosnilimab every four weeks (Q4W), 400mg Q4W, 600mg every two weeks (Q2W), or placebo. The primary endpoint was mean change from baseline DAS-28 CRP assessed at Week 12 compared with placebo and secondary endpoints were ACR20, ACR50 and CDAI LDA assessed at both Week 12 and Week 14 compared with placebo. After the Week 14 visit, rosnilimab-treated patients who achieved CDAI LDA of at most 10 continued their assigned treatment through Week 28 in a blinded, all-active treatment period.¹

"Despite multiple advances in the treatment of patients with RA, a large number remain difficult to treat. Unfortunately, no new drug classes have been approved for RA in the last decade. As we continue to advance our understanding of RA and look to reduce long-term damage to the body’s joints and organs caused by this disease, it is imperative that we develop treatment options with different modes of action, that are not only effective but also safe for long-term use,” Paul Emery, MD, Versus Arthritis professor of rheumatology at the University of Leeds and Leeds Biomedical Research Centre, UK, added.¹ “Rosnilimab’s efficacy data paired with a favorable safety and tolerability profile present a promising new option for people living with RA."

RENIOR achieved its primary endpoint of the mean change from baseline in DAS-28 CRP at Week 12 for all 3 doses of rosnilimab compared with placebo. Rosnilimab also achieved statistical significance in at least 1 dose and numerical superiority at all doses, including once monthly administration, on ACR20, ACR50 and CDAI LDA at Week 12, despite higher than typical placebo rates.Notably, rosnilimab demonstrated the highest ever reported responses for these key secondary endpoints at Week 14, with 69% of rosnilimab-treated patients achieving CDAI LDA at Week 14. CDAI LDA and ACR50 responses seem to be sustained so far, with potentially deepening ACR70 responses out to Week 28.¹

Translational blood biomarker data across all doses demonstrated robust on-target pharmacological activity in the rosnilimab groups not observed in the placebo group, namely rapid and sustained reduction of around 90% of PD-1high T cells and around 50% of PD-1+ T cells, an increase in total Tregs, and around a 50% reduction in the mean C-reactive protein from baseline.¹

"Today’s data offer new hope for patients living with RA and I am particularly encouraged by the combined efficacy and safety profile in both b/tsDMARD-naïve and -experienced patients. This advance in our understanding of RA would not have been possible without the patients and clinicians who participated in this important trial, and we are sincerely grateful,” Paul Lizzul, MD, PhD, chief medical officer of Anaptys, added.¹ “Importantly, these positive clinical and translational data validate our scientific approach to target the PD-1 co-inhibitory receptor on activated immune cells in RA, as well as other heterogeneous, systemic autoimmune and inflammatory diseases, including UC, that would benefit from this novel approach targeting a central node of inflammation.”

Rosnilimab continued to demonstrate a favorable safety and tolerability profile consistent with prior studies, with no evidence of malignancies, major adverse cardiovascular events, elevation of serious infections compared with placebo, or anaphylaxis or systemic hypersensitivity associated with rosnilimab through week 12. There was also a low incidence of injection site reactions which was similar to that seen in the placebo group. Anaptys plans to announce full Week 28 and additional translational data in the second quarter of 2025.¹

REFERENCES

1. Anaptys Announces Rosnilimab Achieved Positive Results in RA Phase 2b Trial and Highest Ever Reported CDAI LDA Response Over 6 Months. News release. Anaptys. February 12, 2025. https://www.globenewswire.com/news-release/2025/02/12/3024946/0/en/Anaptys-Announces-Rosnilimab-Achieved-Positive-Results-in-RA-Phase-2b-Trial-and-Highest-Ever-Reported-CDAI-LDA-Response-Over-6-Months.html

2. A Study of Efficacy and Safety of Rosnilimab in Subjects with Moderate to Severe Rheumatoid Arthritis (RENOIR). Clinicaltrials.gov. https://clinicaltrials.gov/study/NCT06041269