Targeting PD-1 in Rheumatoid Arthritis Save

The results of the large Phase 2b RENOIR trial showed that rosnilimab, a monoclonal antibody targeting PD-1, was effective in moderate-to-severe rheumatoid arthritis (RA) patients.

The manufacturer, Anaptys, issued a press release regarding rosnilimab, a drug being developed for use in inflammatory diseases including rheumatoid arthritis (RA) and ulcerative colitis. Rosnilimab is a depleter and agonist of PD-1+ T cells.  PD-1 agonists target the programmed cell death protein 1 (PD-1) receptor, a co-inhibitory receptor expressed on the surface of activated immune cells. 

This 6 month, multinational trial enrolled 424 RA moderate-to-severe RA patients on background conventional disease-modifying antirheumatic drugs (cDMARDs) such as methotrexate.  Most patients (59(%) were naive to biologic or targeted synthetic DMARD (b/tsDMARD) Patients 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 the DAS-28 CRP at Week 12. At week 14, rosnilimab-treated patients who achieved CDAI low disease activity (LDA) of ≤ 10, continued their assigned treatment through Week 28 in a blinded, all-active treatment period. 

At week 12, all 3 doses of rosnilimab were superior to placebo for:

• Change in DAS-28 CRP: 100 mg -2.06, 400 mg -2.12, 600 mh -2.06 vs placebo -1.69 
• CDAI < 10: 100 mg 46%; 400 mg 50%; 600mg38%;  vs placebo 31%
• ACR20: 100 mg 69%; 400 mg 70%; 600 mg 75%; vs placebo 53% 

Adverse events were low and reasonable, with only 5 serious adverse events noted in the trial. Overall, there were no malignancies, MACE or anaphylaxis events.