With approximately 10% of Europeans living with an autoimmune disease,1 an effective and safe treatment is imperative. Now, in a human clinical trial, a new compound targeting CD40L has reduced disease activity in rheumatoid arthritis (RA) patients without inducing serious adverse events.
In an initial Phase Ia study 59 healthy participants received either a single dose of the compound VIB4920 or placebo. Following this, a second study involving 57 participants with RA was conducted as a proof-of-concept trial. Individuals were given seven doses of various concentrations of VIB4920 or placebo.
Dose-dependent decreased IgG levels in participants from the Phase Ia trial showed that VIB4920 suppressed immune response to a T cell-dependent antigen. Further evidence to support the dampening of immune response in this trial includes that circulating dividing B cells, memory B cells, and plasma cells were all decreased following a dose of VIB4920.
In the following Phase Ib trial, VIB4920 significantly decreased rheumatoid factor autoantibodies in a dose-dependent manner in the RA participants. In addition, VIB4920 induced decreases in Vectra DA biomarker scores, an assay that measures 12 key proteins associated RA disease activity. By Week 12, over 50% of those treated with the two highest doses of VIB4920 achieved low disease activity or clinical remission.
The CD40/CD40L pathway is central to the immune response to antigens and has been targeted for the treatment of autoimmune disease by anti-CD40L monoclonal antibodies many times prior to this study. However, previous studies have been stopped before their finish date because of adverse events occurring, the cause being primarily thromboembolic events related to platelet aggregation. The Fc-domain of antibody molecules has been identified to be the cause of the adverse platelet aggregation events. To avoid such complications, VIB4920 was developed to lack an Fc-domain, which resulted in no adverse thromboembolic events reported in pre-clinical, Phase Ia, or Ib trials.
Summing up their findings, the authors wrote: “VIB4920 represents an alternative to monoclonal antibody–based targeting of CD40L, which does not induce platelet aggregation in vitro and demonstrates a favourable safety profile in early clinical evaluation.” These studies suggest that VIB4290 has the potential to be a safe and effective treatment of many autoimmune diseases, including RA.
- Prevalence of diagnosed autoimmune conditions in selected countries as of 2018. 2019. Available at https://www.statista.com/statistics/418328/diagnosed-autoimmune-conditions-prevalence-in-selected-countries/. Last accessed: 03 May 2019.
