Dr. David R. Jayne discusses his study on an anti-CD40 antibody in lupus nephritis, highlighting the power of negative studies. They talk about challenges in conducting trials, measurement of anti-drug antibodies, embracing failures in science, and the importance of publishing negative results.
Negative studies can provide valuable insights into the challenges of conducting clinical trials.
The 180 milligram dose of BI655064 showed the best efficacy-safety trade-off in reducing proteinuria and anti-double-stranded DNA antibodies in lupus nephritis patients.
Deep dives
The drug BI655064 targets the CD40 CD40 ligand pathway to treat lupus nephritis
BI655064 is a second-generation humanized antagonistic anti-CD40 monoclonal antibody designed to block the CD40 CD40 ligand interaction. It has shown promise in reducing proteinuria and improving clinical endpoints in lupus nephritis patients. Unlike the prior agent BG9588, BI655064 does not cause thrombotic events and has shown effectiveness in reducing anti-double-stranded DNA antibodies.
Design and outcomes of the phase two trial of BI655064 in lupus nephritis
The phase two trial enrolled patients with active lupus nephritis and evaluated different doses of BI655064 in combination with standard of care treatment. While the trial failed to demonstrate a dose-response relationship for the primary endpoint of complete renal response at 52 weeks, the 180 milligram dose showed the best efficacy-safety trade-off. Biomarker analysis revealed reductions in proteinuria and anti-double-stranded DNA antibodies in the 180 milligram group. Adverse events, particularly infections and cytopenias, were more common in the higher dose arms.
Lessons learned and future directions for lupus nephritis trials
Despite not meeting its primary endpoint, the study provided valuable insights into the CD40 CD40 ligand system and the challenges of conducting lupus nephritis trials. The trial demonstrated proof of concept and dose selection, highlighted the complexities of trial design, and called for reevaluating endpoints in future studies. The importance of publishing negative results and exploring biomarkers from seemingly negative studies was emphasized. The study team remains hopeful about the therapeutic potential of BI655064 and the continued advancement of lupus nephritis research.