VDJ-001 is an innovative humanized IgG1 monoclonal antibody that exhibits higher affinity and greater potency in interacting with IL-6R, achieved through a technology that mimics B cell hypermutation.

In a Phase II study (NCT05957107; Completed), both doses of VDJ-001 were found to be safe and well-tolerated, with most experiencing mild adverse reactions (grade I-II). Their safety profile was similar to that of the group treated with tocilizumab, and management was effective even during COVID-19 restrictions. Compared to a placebo group with less than 60% responders, patients treated with either dose of VDJ-001 or Tocilizumab showed significantly improved efficacy (p <0.05) in achieving an ACR20 response (over 80% responders).

Furthermore, there was a noticeable trend in efficacy among ACR50/70 responders, with VDJ-001 6mg/kg showing the highest response rates (64.3% for ACR50 and 33.3% for ACR70), followed by Tocilizumab 8mg/kg, VDJ-001 4mg/kg, and then placebo. The study also found a strong correlation between the pharmacokinetics and pharmacodynamics (sIL-6R) of VDJ-001 and Tocilizumab in a dose-dependent manner. Additionally, changes in the disease biomarker ESR were closely related to the corresponding efficacy of the treatments.

Conclusion

Patients refractory to csDMARDS or with severe symptoms are usually treated with a wide variety of biologic DMARD classes, such as anti-TNF, T-cell inhibitors, B-cell Inhibitors, interleukin inhibitors, and targeted synthetic DMARDs like JAK Inhibitors. Among interleukin inhibitors, tocilizumab is widely used in rheumatoid arthritis. Tocilizumab sales experienced a decline in 2023 following the FDA's approval of the first tocilizumab biosimilar produced by Biogen in late September 2023. This biosimilar is administered via intravenous infusion. The approval of TYENNE (tocilizumab-aazg) was supported by outcome and safety data from numerous clinical studies. Tocilizumab and its biosimilar could compete with VDJ-001 after approval.

VDJ-001 demonstrated not only a safety profile comparable to Tocilizumab but also similar and notably superior efficacy compared to a placebo. Currently, approved medications have a relatively low ACR70, and improving the ACR70 response rate is a particular issue in patients with moderate to severe Rheumatoid Arthritis who do not respond well to methotrexate or DMARDS. 

The proportion of ACR70 response rates in the 6 mg/kg group of VDJ-001 was 33.3%, which exceeded the 25.6% of the 8 mg/kg group of tocilizumab. Given that this response rate is greater than previous Phase III clinical data of approved medications, VDJ-001 could end up being the most effective Rheumatoid Arthritis therapy in its class.