Otsuka Pharmaceutical Co., Ltd. (Otsuka) announces that the Japanese Ministry of Health, Labor, and Welfare (MHLW) has approved Lupkynis^® (voclosporin) for the treatment of lupus nephritis (LN), an inflammation of the kidneys caused by systemic lupus erythematosus, an autoimmune disease.

Lupkynis is a novel, oral immunosuppressive agent developed for the treatment of LN. It suppresses the immune system by inhibiting calcineurin, an enzyme that is crucial for the proliferation and activation of T cells, an important element of the immune system.

In the U.S., Aurinia Pharmaceuticals Inc. (Aurinia) received FDA marketing approval in January 2021 for Lupkynis as a treatment for active LN in adults. In September 2022 Otsuka received European Commission (EC) approval for Lupkynis as the treatment for active LN in EU member countries. Otsuka has subsequently received reimbursement in several EU countries as well as in the UK.

In December 2020, Otsuka and Aurinia announced that they entered into a collaboration and license agreement for the development and commercialization of oral voclosporin for the treatment of LN in Japan, the European Union (EU), and the UK, Russia, Switzerland, Norway, Belarus, Iceland, Liechtenstein and Ukraine.

Otsuka Pharmaceutical has been committed to research and development that contributes to patients and their families in order to meet unmet medical needs worldwide, focusing on cardiovascular, renal and autoimmune diseases as one of which are among our priority areas.

About lupus nephritis

Lupus nephritis (LN) is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE). The kidneys are vital organs, and LN is an irreversible and progressive condition that puts them at risk for long-term complications. If left untreated, this kidney inflammation impairs kidney function and can lead to permanent kidney damage and even kidney failure, known as end-stage renal disease (ESRD). LN is one of the most serious complications of SLE.

In Japan, the number of SLE patients is estimated to be between 60,000 and 100,000, with women accounting for 90% of cases. It is particularly prevalent among women aged 20 to 40.¹ Asians have a higher incidence of renal involvement compared to Caucasians, with 21% to 65% of Asian patients (living in Asia) with SLE having developed LN by the time of diagnosis, and 40% to 82% developing it over time.² The development of LN in SLE patients often occurs at a relatively young age and is believed to increase the risk of end-stage renal failure, leading to a deterioration in life expectancy. The challenge is to achieve rapid remission of glomerulonephritis with reduction in proteinuria, while avoiding long-term use of high doses of steroid medication.

About the clinical trials AURORA 1 and AURORA 2^{3, 4}

The MHLW approval is based on data from clinical trials, including AURORA 1 and AURORA 2.

The AURORA 1 international phase 3 trial was conducted with the primary endpoint of renal response at 52 weeks. A total of 357 patients with active LN from age 18 to 75 were enrolled in the trial, of whom 179 patients and 178 patients were randomly assigned to the voclosporin and placebo groups, respectively.

Both the voclosporin group and the placebo group were co-administered with mycophenolic mofetil and oral steroids during the trial, with a regimen to reduce the dose of steroids. The proportion of patients achieving renal response at 52 weeks was significantly higher in the voclosporin group at 40.8% compared to 22.5% in the placebo group (p＜0.001).

AURORA 2 evaluated the long-term safety, tolerability, and efficacy of voclosporin compared to placebo in 216 patients with LN (116 in the voclosporin group and 100 in the placebo group) who received an additional 2 years of treatment following completion of AURORA 1. The long-term safety and tolerability was assessed and no new or unexpected safety signals were observed.

• Reference
  1. Information Center for Rare Diseases https://www.nanbyou.or.jp/entry/53 (as of September 2024)
  
• 2. Jakes, RW. et al.:Arthritis Care Res. 2012; 64(2): 159-168
• 3. Brad H Rovin, Y K Onno Teng, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-bling, randomized, multicenter, placebo-controlled, phase 3 trial. Lancet 2021; 397: 2070-80
• 4. Amit Saxena, Ellen M. Ginzler, et al. Safety and efficacy of long-term voclosporin treatment for lupus nephritis in the phase 3 AURORA 2 clinical trial. Arthritis & Rheumatology Vol. 76, No. 1, January 2024, pp 59-67