Janssen Pharmaceutical Companies of Johnson & Johnson Announces Phase 2 Nipocalimab Data Establish Proof Of Mechanism In Adults Living With Moderate To Severe Rheumatoid Arthritis, Supporting Its Progression Into A Combination Study

This first-ever clinical study of an FcRn inhibitor in RA showed nipocalimab reduced levels of circulating IgG antibodies, including ACPAs, indicating they may play a key role in driving RA disease activity

Nipocalimab demonstrated improvements in primary and secondary endpoints and participants with higher baseline ACPAs had more than twice the placebo adjusted DAS28-CRP remission compared to the overall study population

SPRING HOUSE, Pa., Nov. 7, 2023 /PRNewswire/ — The Janssen Pharmaceutical Companies of Johnson & Johnson today announced data from the Phase 2a IRIS-RA clinical study for the treatment of adults living with moderate to severe active rheumatoid arthritis (RA) who have tested positive for anti-citrullinated protein antibodies (ACPAs)a and/or rheumatoid factor (RF), and who have had an inadequate response or intolerance to at least one anti-tumor necrosis factor (anti-TNF) therapy. The data from this study establish proof of mechanism for nipocalimab in RA and support its progression into a combination study.1 IRIS-RA is the first clinical study to assess the efficacy and safety of the anti-neonatal Fc (FcRn)-driven MOA for the treatment of RA.2 The study findings, along with an acceptable benefit-risk profile, support the further investigation of nipocalimab in this refractory population.1 A trial investigating the efficacy and safety of nipocalimab in combination with an anti-TNFα treatment in patients living with RA has recently been initiated.3

Treatment with nipocalimab, an anti-FcRn receptor therapy, resulted in numerically greater improvements at Week 12 across primary and secondary efficacy endpoints including Disease Activity Score 28 using C-reactive protein (DAS28-CRP),b American College of Rheumatology (ACR) responses,c DAS28-CRP remission and Health Assessment Questionnaire – Disability Index (HAQ-DI).1,d A numerically greater number of patients in the nipocalimab group achieved ACR50 (n=5/33 nipocalimab versus n=1/20 placebo) and DAS28-CRP remission (n=7/33 nipocalimab versus n=2/20 placebo) compared with the placebo group.1 

By selectively blocking the FcRn receptor, nipocalimab reduced levels of circulating immunoglobin G (IgG) antibodies, including ACPAs, indicating they may play a key role in driving RA disease activity.4 The placebo adjusted DAS28-CRP remission rate of a subpopulation of study participants with higher mean baseline levelse of ACPAs was more than double the overall study population (23.3 percent difference from placebo [n=27]; versus 11.2 percent difference from placebo [n=53] respectively).1,4

These data will be presented for the first time as an oral presentation at ACR Convergence 2023, taking place in San Diego, California on November 12, 2023.1 In addition, a poster (#2144) on the pharmacodynamic effects of nipocalimab in the IRIS-RA study will be presented at ACR.1,4

“There is an urgent need for new therapeutic avenues capable of reducing the impact of rheumatoid arthritis for more patients,” said Dr. Peter C. Taylor, MA, Ph.D., FRCP, FRCPE, Norman Collisson Professor of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford.f “Even with the use of the current targeted therapies, up to half of those living with rheumatoid arthritis do not reach remission or still have low disease activity. We believe autoantibodies are major contributors to this disease activity and current rheumatoid arthritis treatments like TNF inhibitors generally don’t effectively reduce autoantibodies. These encouraging results are the first time that the selective reduction of IgG autoantibodies has shown evidence of efficacy in a clinical study and are the first ever from a clinical study of an FcRn inhibitor in rheumatoid arthritis indicating nipocalimab has the potential to improve disease activity through a novel mechanism of action.”

IRIS-RA clinical trial results at Week 12:
At Week 12, the IRIS-RA data show that treatment with nipocalimab resulted in consistent and numerically higher improvements across change from baseline in DAS28-CRP score (Table 1) and HAQ-DI (Supplement, Table 1) as well as ACR responses (Supplement, Table 2), compared to placebo.1 The data also highlighted the differential response to treatment with nipocalimab for patients with higher baseline levels of ACPAs (Table 2).1,4

PK/PD simulation based on data from previous nipocalimab studies predicted median total IgG reduction of 64 percent at the trough (the timepoint at which the concentration of nipocalimab is at its lowest) and 76 percent at the peak with 15mg/kg IV nipocalimab.4 IRIS-RA study data are consistent with the model predictions and showed 62 percent reduction (median) in total IgG at the trough.4

Nipocalimab demonstrated an acceptable benefit-risk profile:

• The proportion of patients with treatment-emergent adverse events was 27 out of 33 (81.8 percent) in the nipocalimab group versus 12 out of 20 (60 percent) in the placebo group.1
• In the nipocalimab group, three serious treatment-emergent adverse events were reported, including burn infection, infusion-related reaction and deep-vein thrombosis.1 There were no deaths.1 No serious adverse events were reported in the placebo group.1
• Nipocalimab did not have a clinically meaningful impact on albumin (-1.83 percent in nipocalimab versus 1.54 percent in placebo mean change from baseline to Week 18)5 or total cholesterol (-2.34 percent in nipocalimab versus 3.13 percent in placebo mean change from baseline to Week 18).6

“Significant patient need remains for those suffering from rheumatoid arthritis and our research shows autoantibodies like ACPAs may contribute to the development and activity of rheumatoid arthritis,” said Terence Rooney, M.D., Vice President, Rheumatology Disease Area Leader, Janssen. “Current treatments, like TNF-inhibitors, may not markedly reduce autoantibodies when used alone so these results are promising for patients who have had inadequate responses to other advanced therapies. The combination of nipocalimab with therapies that have a complementary MOA, such as anti-TNFs, will be of interest as we explore alternative avenues of treatment for patients with rheumatoid arthritis, and we are excited to have initiated the Phase 2a DAISY-RA trial to explore this combination. We are also encouraged by the efficacy of nipocalimab in the autoantibody high subpopulation, providing a potential precision-medicine approach to treating patients.”

Janssen recently initiated a Phase 2a proof-of-concept trial, DAISY-RA (NCT06028438), investigating the efficacy and safety of nipocalimab in combination with an anti-TNFα treatment in patients living with RA who have had an inadequate response or intolerance to at least one advanced disease-modifying antirheumatic drug therapy.3 The DAISY-RA trial is currently ongoing and is recruiting patients in the study.3

Nipocalimab is the only anti-FcRn currently being studied across three key disease segments: maternal fetal immune, rare autoantibody and prevalent rheumatic diseases and is the only anti-FcRn being studied in pregnant individuals at high risk of hemolytic disease of the fetus and newborn