Voclosporin is a novel therapy in development for patients with lupus nephritis, an inflammation of the kidney which is one of the most serious complications of the autoimmune disease systemic lupus erythematosus (SLE). If left untreated, lupus nephritis can lead to irreversible kidney damage, kidney failure or even death. Through an extensive clinical program, voclosporin has demonstrated superiority to the standard-of-care for lupus nephritis. It is now under review by the FDA with Fast Track status and Priority Review as a potential first-ever approved oral therapy for lupus nephritis in the United States.
Voclosporin’s novel design gives it a highly differentiated profile, supported by an extensive clinical program. Its advantages as a potential treatment for lupus nephritis include:
Calcineurin is a signaling protein involved in T cell activation, a key immune cell in the body. By inhibiting calcineurin, voclosporin blocks the expression of a pro-inflammatory signaling molecule called IL-2 and reduces immune responses mediated by T cells. Emerging data suggests it also stabilizes the structure of podocytes – an important cell type in the kidney – protecting against their destruction. Voclosporin has a favorable metabolic profile and a consistent, predictable dose response which potentially eliminates the need for the therapeutic drug monitoring seen with legacy CNIs.
In patients with lupus nephritis, kidney damage may start prior to the first clinically detected episode of lupus nephritis. Kidney degeneration is progressive, and reduced function is associated with poor long-term outcomes. Kidney biopsy is the standard for confirming lupus nephritis diagnosis, and a kidney biopsy delay longer than six months is associated with a 9 times greater risk of progression to kidney failure. A person whose kidney degenerates to the point of kidney failure has a risk of premature death more than 60 times higher than normal. Therefore, patients should be actively and routinely screened for signs of the disease, and if diagnosed, immediately managed. Patients with lupus nephritis who achieve a complete response as measured by decreases in proteinuria (protein in the urine) and a urine protein-to-creatinine ratio (UPCR) of less than 0.5 gm/gm can achieve better long-term kidney outcomes such as avoidance of kidney failure, dialysis or need for transplantation, which all have severe impact on a person’s health and quality of life, in addition to incurring significant healthcare system costs.
Find out more about lupus nephritis here.
The introduction of calcineurin inhibitors (CNIs) in the late 1970s revolutionized the field of organ transplantation – improving patient outcomes and becoming a mainstay immunosuppressive therapy for the next 40 years. However, chronic treatment with legacy CNIs is associated with side effects which can limit their long-term use and benefits. Voclosporin is a novel, next-generation CNI with pharmacological properties that strongly differentiate it from legacy CNIs and uniquely positions it as a potential treatment for people living with lupus nephritis.
After decades of research in thousands of patients with various conditions, in late 2019 Aurinia reported uniformly positive results from the AURORA trial of voclosporin – the first late-stage clinical trial of any drug in lupus nephritis to meet all primary and secondary endpoints. The study was designed to evaluate whether voclosporin when added to background therapy of mycophenolate mofetil (MMF)/CellCept® could increase speed of and overall renal response rates in the presence of low dose steroids. MMF is the current standard-of-care for lupus nephritis in the United States although not approved for that use. In addition to demonstrating superiority to MMF across all endpoints, voclosporin was also well-tolerated with no unexpected safety signals.