Aurinia Pharmaceuticals has announced that in addition to low-dose voclosporin (23.7 mg twice daily) achieving its primary endpoint of complete remission (CR) at 24 weeks in the AURA-LV trial, both low-dose and high-dose (39.5 mg twice daily) voclosporin, when added to the current standard of care of mycophenolate mofetil and a forced oral corticosteroid taper, have met all 24-week secondary endpoints compared with the control group. These endpoints included partial remission (PR); time to CR and PR; the reduction in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score; and the reduction in the urine protein/creatinine ratio (UPCR) during the 24-week treatment period.
Voclosporin, an investigational calcineurin inhibitor, is being developed for the treatment of patients with lupus nephritis.
In the new study, the time to CR was 19.7 weeks for low-dose voclosporin and 23.4 weeks for high-dose voclosporin compared with “not achieved” for the control group (P < 0.001 and P = 0.001 for the two voclosporin doses versus control). PR was achieved by 70% of the low-dose group (P = 0.007) and by 66% of the high-dose group (P = 0.024) compared with 49% of the control group. The time to PR was 4.1 weeks and 4.4 weeks for low-dose voclosporin (P = 0.002) and high-dose voclosporin (P = 0.003), respectively, compared with 6.6 weeks for the control group. The SLEDAI reduction was –6.3 and –7.1 for low-dose and high-dose voclosporin (both P = 0.003) compared with –4.5 for control. The reduction in UCPR was –3.769 mg/mg for low-dose voclosporin (P < 0.001) and –2.792 mg/mg for high-dose voclosporin (P = 0.006) compared with a reduction of –2.216 mg/mg for the control group.
The AURA-LV study remains ongoing to its 48-week endpoint.
Voclosporin acts as an immunosuppressant by blocking interleukin-2 expression and T-cell–mediated immune responses. It is made by a modification of a single amino acid of the cyclosporine molecule. Auriana Pharmaceuticals anticipates that if voclosporin is approved for the treatment of patients with lupus nephritis, patent protection will be extended in the United States until at least October 2027 under the Hatch–Waxman Act.
Lupus nephritis is inflammation of the kidney caused by systemic lupus erythematosus (SLE) and represents a serious progression of SLE. SLE is a chronic, complex, and often disabling disorder that affects more than 500,000 people in the U.S. (mostly women). The disease is highly heterogeneous, affecting a wide range of organs and tissue systems. It has been estimated that as many as 60% of all SLE patients have clinical lupus nephritis requiring treatment. In patients with lupus nephritis, renal damage results in proteinuria and/or hematuria and decreased renal function, as evidenced by a reduced estimated glomerular filtration rate and increased serum creatinine levels.
Source: Aurinia Pharmaceuticals; September 29, 2016.