Antiviral Effects of Voclosporin on SARS-CoV-2 in Immunocompromised Kidney Patients

ABSTRACT

Background: Immunocompromised patients, including Kidney Transplant Recipients (KTRs) and lupus nephritis (LN) patients, are at increased risk for prolonged SARS-CoV-2 infection and developing COVID-19-related complications. Recently, we reported that voclosporin, a novel calcineurin inhibitor (CNI), demonstrated in vitro a more potent inhibitory effect on SARS-CoV-2 replication than other CNIs (tacrolimus and ciclosporin). Additionally the AURORA-2 study, where 216 LN patients were treated with voclosporin or placebo on top of standard of care, SARS-CoV-2 infection was detected in 12/100 placebo-treated patients (12%) compared to 7/116 voclosporin treated patients (6%) and more patients died due to COVID-19 in the placebo arm versus voclosporin arm (3% vs 0%). In this proof-of-concept study we assessed whether voclosporin demonstrated an added antiviral benefit in SARS-CoV-2 positive immunocompromised patients. Method(s) We performed a prospective, randomised, open-label, single-center, exploratory, proof of concept study in 20 KTRs with mild to moderate symptoms from a COVID-19 infection comparing time to viral clearance of SARS-CoV-2 between patients on standard immunosuppressive therapy with tacrolimus versus voclosporin (the VOCOVID study). Result(s) In the VOCOVID study no difference in time to viral clearance or time to clinical recovery was found between both treatment arms. Pharmacokinetic analysis demonstrated that adequate trough levels of voclosporin were reached from day 4-8 after randomization. Looking at specific timepoint in a post-hoc analysis, indeed a significantly better viral clearance of SARS-CoV-2 was observed in voclosporin treated patients at day 4-8. No safety concerns were raised. Conclusion(s) The present study provides evidence that voclosporin has a favorable benefit-risk profile for immunocompromised kidney disease patients who contract a SARS-CoV-2 infection while requiring the continuation of their immunosuppressants.