By doing this, the drug is designed to reduce the amount of autoantibodies commonly observed in the blood of patients with RA, such as anti-citrullinated protein antibodies (ACPAs).
"There is an urgent need for new therapeutic avenues capable of reducing the impact of rheumatoid arthritis for more patients," said Peter C. Taylor, Norman Collisson professor of musculoskeletal sciences at the University of Oxford, and paid consultant for Janssen, in a public release.
"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 [tumor necrosis factor] inhibitors generally don't effectively reduce autoantibodies.”
The trial results
The trial enrolled patients with moderate to severe RA who had tested positive for ACPAs and/or rheumatoid factor (RF) – another protein linked to the development of the disease. Eligible patients had previously failed to respond to previous therapies blocking tumor necrosis factor.
The group given the antibody drug candidate (33 patients) showed a lower disease severity at week 12 than the group given a placebo (20 patients), indicated by a -0.45 difference on the Disease Activity Score 28 with C-reactive protein (DAS-28-CRP). However, the difference wasn’t statistically significant.
Janssen reported numerically greater improvements with nipocalimab in secondary endpoints, including the proportion of patients who achieved American College of Rheumatology (ACR)20, ACR50, ACR70, and ACR90 responses, DAS28-CRP remission, and more.
Nipocalimab also reduced blood levels of immunoglobulin G (IgG) antibodies, including ACPAs, which suggests a link between them and RA activity. In fact, the antibody drug candidate showed a bigger DAS28-CRP remission rate in patients with higher blood levels of ACPAs.
The candidate also showed an acceptable benefit-risk profile with no deaths and three serious treatment-emergent adverse events including burn infection, infusion-related reaction and deep-vein thrombosis.
Worth exploring further
While not all results met statistical significance thresholds, Janssen’s EMEA Therapeutic Area Lead for Immunology, Ludovic de Beaucoudrey, explained in an email that the study provides the scientific community with valuable data in this setting and indicates that it is worth exploring nipocalimab further in this indication.
“In a phase 2 study, results may be highly relevant for understanding the mechanism of action even if they do not turn out to be statistically significant on a specific outcome,” said de Beaucoudrey. “The consistency across endpoints (e.g. DAS28-CRP, ACR50, HAQ-DI) provides support for a potential role for nipocalimab in managing refractory RA.”
Janssen recently began recruiting patients with refractory RA into a phase 2a trial of nipocalimab combined with an anti-tumor necrosis factor α, which is a complementary mechanism of action.
The first FcRn blocker to be approved was argenx’s Vyvgart (efgartigimod), which was greenlit by the US Food and Drug Adminstration (FDA) in 2021 for the treatment of the autoimmune condition generalized myasthenia gravis. Drugs with this mechanism of action have the potential to treat a wide range of conditions involving autoimmunity.
Johnson & Johnson got hold of nipocalimab as its own anti-FcRn candidate in 2020, when it acquired the company Momenta Pharmaceuticals for $6.5 billion.