The immune system is a complex network that is tightly regulated to ensure a correct response when threatened by an external “offender.” This network is composed of cells that act to killing the offender and cells that recognize the “offender” and spread a chemical message to other nearby cells to stop the “offense” — all part of a process called inflammation.
In autoimmune diseases such as lupus, one or more players in this tightly regulated system malfunctions, and the immune system starts recognizing the body’s own proteins as potential threats. The attacks launched on them lead to inflammation and, subsequently, damage to tissues and organs. When inflammation occurs in the kidneys, the disease is called lupus nephritis.
In severe cases of lupus nephritis, a medication that suppresses the immune system is prescribed.
How does voclosporin work?
Calcinurin is an enzyme that activates cells of the immune system called T-cells, which send a chemical signal to other nearby cells that activate them in an effort to stop the “offender.” Voclosporin is an immunosuppressant drug that directly binds to calcineurin, a bond that causes a structural change to calcineurin. Such binding prevents the activation of the immune cells and decreases the production of the chemical signals that spread inflammation from cell to cell.
By reducing the amount of chemical messengers traveling through an organ, voclosporin reduces inflammation in the kidneys and stops further damage from occurring.
Studies with voclosporin
Voclosporin was assessed in a Phase 2 clinical trial, AURA (NCT02141672), to determine the effectiveness of two doses of voclosporin in achieving complete remission of kidney disease after 24 and 48 weeks of therapy in patients with active lupus nephritis.
Trial results demonstrated that voclosporin was well-tolerated, and the drug’s overall safety profile was consistent with other immunomodulating therapies. The optimal dose of voclosporin was established to be 23.7 mg twice daily.
Among patients given the optimal dose, 70 percent achieved partial remission after 24 weeks of treatment and 33 percent achieved complete remission. After 48 weeks, 49 percent of patients on voclosporin, 23.7 mg twice a day, achieved complete remission, compared to 24 percent of those given a placebo.
It took two weeks less for patients undergoing this voclosporin therapy to achieve partial remission than for those in the placebo treatment, and complete remission was achieved in less than 20 weeks in patients given voclosporin as its determined optimal dose.
Another Phase 2 clinical trial (NCT02949973) is assessing the ability of biomarkers measured after eight weeks of treatment to predict clinical response over 24 and 48 weeks in lupus nephritis patients taking voclosporin.
Aurinia announced the beginning of a new and possibly pivotal clinical trial in May 2017. This trial, called AURORA (NCT03021499), is a 52-week, double-blind, placebo-controlled Phase 3 study that will compare the effectiveness of voclosporin (23.7 mg twice daily), plus the current standard of care (mycophenolate mofetil, or MMF), in achieving a renal response at 24 weeks in patients with active lupus nephritis. This trial, like AURA, is likely to be global with sites in the U.S. and Europe, and plans to recruit up to 324 people. More information is available on its clinical trials.gov webpage.
If the AURORA trial is successful, Aurinia is planning to file requests for voclosporin’s approval, under the brand name Orelvo, as a lupus nephritis treatment with the FDA and other regulatory authorities.
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