The US FDA Approved The Inhibitor Lupkynis For The Treatment Of Adult Patients With Active Lupus Nephritis (LN).

- Feb 07, 2021-


Aurinia Pharma is a biopharmaceutical company dedicated to the development of innovative therapies for kidney disease and autoimmune diseases. Recently, the company announced that the U.S. Food and Drug Administration (FDA) has approved Lupkynis (voclosporin), a combined background immunosuppressive treatment program, for the treatment of adult patients with active lupus nephritis (LN).


LN is one of the most serious and common complications of autoimmune disease systemic lupus erythematosus (SLE), which can cause irreversible kidney damage and significantly increase the risk of kidney failure, cardiac events, and death.


In December 2020, the GlaxoSmithKline antibody drug Benlysta (generic name: belimumab) was approved by the US FDA and became the first drug to treat LN. Lupkynis is the first oral therapy approved by the FDA for the treatment of LN.


In a pivotal clinical trial, patients receiving Lupkynis combined with standard care (SoC) therapy are more than twice as likely to achieve renal remission than patients receiving typical SoC treatment, and the rate of urinary protein-creatinine ratio (UPCR) decline is at the rate of receiving typical SoC treats patients twice. UPCR is a standard measurement method used to monitor protein levels in the kidney. Early intervention and renal remission are associated with better long-term results and prevention of irreversible kidney damage. Patients treated with Lupkynis showed improved response rates in all parameters of the studied LN immune activity category.


Lupus nephritis (LN) is a serious kidney inflammation caused by an autoimmune disease-systemic lupus erythematosus (SLE), which represents a serious progression of SLE. If not effectively controlled, it can lead to permanent Irreversible tissue damage, leading to end-stage renal disease (ESRD), life-threatening.


In December 2020, GlaxoSmithKline Benlysta was approved by the U.S. FDA as the first drug to treat LN. The drug is suitable for the treatment of adult patients with active LN who are receiving standard treatment. Benlysta was approved for marketing in 2011 and is the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in the past 50 years. In China, Benlysta (Benlysta, belimumab for injection) was approved in July 2019. As the world's first biological agent approved for the treatment of SLE, Britton has been approved in China to be combined with conventional treatment, which is suitable for active and autoantibody-positive adult patients with SLE who still have high disease activity on the basis of conventional treatment.


The approval of the oral drug Lupkynis is based on the support of an extensive clinical development project, including the pivotal phase III AURORA study and the pivotal phase II AURALV study. AURORA is a global, placebo-controlled, pivotal phase III study. The data shows that when combined with mycophenolate mofetil (MMF) and low-dose oral corticosteroids, voclosporin improves the performance of patients with lupus nephritis compared with placebo. The short-term and long-term prognosis. The specific data are: Compared with placebo, voclosporin significantly increased the renal remission rate (primary endpoint: 40.8% vs 22.5%, p<0.001), and was also statistically significant in all pre-specified hierarchical endpoints improve. In this study, the safety of the voclosporin regimen is comparable to the standard regimen.

voclosporin

voclosporin structure


voclosporin is an investigational drug, which is a new and potentially best-in-class calcineurin inhibitor (CNI) with clinical data of more than 2600 patients in multiple indications . voclosporin is an immunosuppressant with a synergistic and dual mechanism of action. voclosporin stabilizes kidney podocytes by inhibiting calcineurin (CN), blocking IL-2 expression and T cell-mediated immune response. Compared with the traditional CNI, voclosporin has a more predictable pharmacokinetic and pharmacodynamic relationship (therapeutic drug monitoring may not be required), increased potency (compared to cyclosporin a) and improved metabolic profile.


Structurally, voclosporin is an analog of cyclosporine A (cyclosporine A) with an extra single-chain carbon extension with a double bond (ene bond) on the single-carbon chain. voclosporin binds to cyclophilin A (cyclophilin A) to form a heterodimeric complex, which then binds and inhibits calcineurin to exert an immunosuppressive effect. The binding affinity of voclosporin and cyclosporin A to human cyclophilin protein is equivalent, but the ethylenic side chain of voclosporin can induce structural changes of calcineurin when binding, which may lead to Enhanced immunosuppressive activity.


In addition to lupus nephritis (LN), Aurinia is also developing voclosporin eye drops (VOS) for the treatment of dry eye (DES). Currently, there are 3 FDA-approved prescription drugs for the treatment of DES, 2 of which are CNI. VOS has the potential to improve the treatment of DES by reducing the time to achieve objective and subjective relief of DES symptoms and signs.