Frequently asked questions: voclosporin
Voclosporin is an investigational drug that is being tested as a potential new treatment for lupus-related kidney disease (lupus nephritis)
Voclosporin is an immunosuppressant with a synergistic and dual mechanism of action. By inhibiting calcineurin, a protein that activates T-cells, voclosporin blocks IL-2 expression and T-cell mediated immune responses and stabilizes the podocyte (a type of cells) in the kidney. It has been shown to have a more predictable pharmacokinetic and pharmacodynamic relationship. Based on voclosporin’s consistent profile, it potentially requires no therapeutic drug monitoring. It has been shown to have an increase potency (vs cyclosporin) and an improved metabolic profile compared to legacy CNIs.
Voclosporin is being developed for treatment of lupus nephritis by Aurinia Pharmaceuticals headquartered in Vancouver, British Columbia.
Aurinia Pharmaceuticals has completed two previous clinical studies of voclosporin – AURION, an exploratory proof of concept study, and AURA, a global placebo-controlled Phase 2 study to evaluate whether voclosporin added to mycophenolate mofetil (MMF) could increase speed of remission and overall remission rates in the presence of low doses of steroids. AURA was the first global clinical trial in active lupus nephritis to meet its primary endpoint. This third study, AURORA, was a global, double-blind, placebo-controlled study to evaluate whether voclosporin, when added to background therapy of MMF, can increase speed of and overall renal response rates in the presence of low dose steroids.
The study met all of its primary and secondary endpoints, achieving statistical significance across all measures. Voclosporin was well tolerated and had a good safety profile with only a few patients dropping out of the study.
At the present time, there is no therapy approved by the US and European regulators specifically for lupus nephritis. A number of agents developed for other diseases and conditions have been used as therapies for nephritis. These include corticosteroids, azathioprine, mycophenolate mofetil (MMF), and cyclophosphamide. Voclosposin, which has received fast-track designation from the FDA, would be the first and only therapy approved for this disabling and life-threatening condition.
Voclosporin is a targeted therapy that works against a protein in the immune system called calcineurin. This protein activates T-cells that contribute to an autoimmune response. By blocking this activation, voclosporin mediates the autoimmune response and potential damage to the kidneys.
The results from the AURORA study and other clinical trial data for voclosporin will be submitted to the U.S. Food and Drug Administration (FDA) for review in the first half of 2020. Voclosporin has Fast Track designation by the FDA, which facilitates expedited review and development of drugs which treat a serious or life-threatening condition and fill an unmet medical need. ONLY after receiving FDA approval will the drug be available to patients. Aurinia is preparing for voclosporin to potentially be available to patients in the first half of 2021.
Overall voclosporin was found to be well-tolerated, with no unexpected safety signals observed. Safety results are detailed in Aurinia’s press release.
None of the deaths in the trial (5 on placebo, 1 on treatment) were deemed to be treatment-related.
There are several promising treatments in the near-term pipeline. More companies are involved in lupus research and there are more potential new therapies being investigated than ever before.
Lupus is a complex disease. It can affect multiple organ systems and symptoms can range in severity from one day to the next. And it can affect each person differently with varying responses to treatment. The complexity presents challenges in evaluating potential new therapies. With each research study, regardless of the outcome, there are new discoveries that help pave the way for new therapies.