What Is Voclosporin?
Voclosporin is an investigational medication that acts as a calcineurin inhibitor. This means it works by suppressing the immune system, which can be beneficial in conditions where the immune system is overactive or causing harm. It has been previously studied to prevent acute rejection in patients who receive a kidney transplant. Currently, voclosporin is being investigated for the treatment of various conditions, including Lupus Nephritis, psoriasis, and keratoconjunctivitis sicca. Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) that affects about half of patients with SLE. LN can increase the risk of morbidity and mortality, especially if it progresses to chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Some studies are also exploring its use in a compassionate release program for patients who previously participated in kidney transplant studies.
Uses and Conditions Under Study
Voclosporin is being studied for its potential to treat several conditions, primarily those involving immune system dysfunction.
A major focus of research is on Lupus Nephritis, with a total of 7 trials investigating its use in adults, and an additional 4 trials for pediatric and adolescent patients. Lupus nephritis is a severe kidney inflammation caused by systemic lupus erythematosus, where the immune system attacks the kidneys. As a calcineurin inhibitor, voclosporin aims to suppress this immune response and protect kidney function.
Several other kidney-related conditions are also under investigation. These include Focal Segmental Glomerulosclerosis, Kidney Diseases, Kidney Transplant Infection, Renal Transplantation, and general Immunosuppression, with a combined total of 5 trials. In these conditions, voclosporin's ability to modulate the immune system could help prevent rejection of transplanted organs, manage kidney inflammation, or provide necessary immunosuppression.
Psoriasis is another condition being studied, with 3 trials. Psoriasis is a chronic autoimmune disease that causes skin cells to build up rapidly, forming thick, silvery scales and itchy, dry patches. Voclosporin's immunosuppressive properties may help reduce the inflammation and overactive cell growth seen in psoriasis.
Finally, Keratoconjunctivitis Sicca, commonly known as dry eye syndrome, is being explored in 2 trials. This condition involves inflammation of the cornea and conjunctiva due to insufficient tear production or excessive tear evaporation. By modulating the immune response, voclosporin may help reduce the inflammation contributing to dry eye symptoms.
Dosing
Voclosporin has been studied in various dosage forms and strengths, primarily as oral capsules and an ophthalmic solution.
For adults, voclosporin is generally administered orally at a dose of 23.7 mg twice daily (BID). This oral dosage is often used in combination with other medications such as corticosteroids and mycophenolate mofetil (MMF). Some trials have also investigated oral doses of 15.8 mg BID. The dosage may be adjusted based on the patient's condition, with provisions for dose reduction or temporary interruption if safety concerns arise, particularly related to blood pressure and renal function. Oral formulations like QL1074 23.7 mg BID have been administered as a fixed dose without therapeutic drug monitoring in some studies.
In addition to oral capsules, voclosporin has been studied as an ophthalmic solution (VOS) for conditions like keratoconjunctivitis sicca. Strengths investigated include 0.05% to 0.20% VOS.
For pediatric and adolescent patients, investigational doses have been studied based on body weight, including ranges from 0.25 mg/kg to 1.5 mg/kg voclosporin. Specific weight-based oral doses such as 0.2 mg/kg po BID, 0.3 mg/kg po BID, and 0.4 mg/kg po BID have also been explored. These studies often involve different treatment arms, such as "Low Dose Voclosporin," "Mid Dose Voclosporin," and "High Dose Voclosporin," to evaluate efficacy and safety across a range of dosages.
Side Effects
In clinical trials involving patients taking Voclosporin, the most commonly reported side effect was nasopharyngitis (common cold symptoms). Overall, side effects were generally mild to moderate in severity.
- Nasopharyngitis (common cold symptoms) occurred in 25.9% of patients taking Voclosporin, compared to 23.5% of patients on placebo.
- A decrease in glomerular filtration rate (a measure of kidney function) was observed in 18.4% of patients taking Voclosporin in some studies, compared to 7.2% on placebo. In other studies, this decrease was seen in 12.1% of Voclosporin patients, versus 5.9% on placebo.
- Headache was reported by 14.6% of patients taking Voclosporin, compared to 8.1% on placebo.
- Hypertension (high blood pressure) occurred in 12.6% of patients taking Voclosporin, versus 7.3% on placebo.
- Upper respiratory tract infection affected 12.4% of patients taking Voclosporin, compared to 9.7% on placebo.
- Diarrhea was experienced by 11.4% of patients taking Voclosporin, compared to 8.9% on placebo.
- Anemia (low red blood cell count) was reported in 11.0% of patients taking Voclosporin, compared to 4.6% on placebo.
Other side effects reported include nausea (8.5% on Voclosporin vs 7.9% on placebo) and cough (7.9% on Voclosporin vs 2.7% on placebo).
Clinical Trial Results
Voclosporin in Plaque Psoriasis
A randomized, placebo-controlled study (NCT00244842) investigated Voclosporin in patients with plaque psoriasis. The study assessed the proportion of subjects achieving a 75% improvement in Psoriasis Area and Severity Index (PASI-75) at 12 weeks. Four participants on placebo achieved PASI-75. Among those taking Voclosporin, 14 participants at the 0.2 mg dose, 26 participants at the 0.3 mg dose, and 44 participants at the 0.4 mg dose achieved PASI-75.
Voclosporin in De Novo Renal Transplantation
In a study (NCT00270634) evaluating Voclosporin in patients undergoing de novo renal transplantation, different doses of Voclosporin were compared to tacrolimus. Key findings included:
- The rate of biopsy-proven acute rejection (BPAR) was lowest in the high-dose Voclosporin group at 2.3%, compared to 5.8% for tacrolimus, 10.7% for low-dose Voclosporin, and 9.1% for mid-dose Voclosporin.
- Graft survival was high across all groups: 100% for low-dose and mid-dose Voclosporin, 98.9% for high-dose Voclosporin, and 97.7% for tacrolimus.
- Patient survival also showed high rates: 100% for low-dose and mid-dose Voclosporin, 98.9% for high-dose Voclosporin, and 97.7% for tacrolimus.
Voclosporin in Lupus Nephritis (AURA-LV Study)
The AURA-LV study (NCT02141672) examined Voclosporin in patients with lupus nephritis. Results indicated that:
- Patients taking Voclosporin achieved partial remission faster. The median time to partial remission was 4.3 weeks for low-dose Voclosporin and 4.4 weeks for high-dose Voclosporin, compared to 6.6 weeks for placebo.
- For patients who achieved complete remission, the median duration of remission was 49 weeks for low-dose Voclosporin and 25 weeks for high-dose Voclosporin. The median duration was not reached for placebo.
- Regarding sustained early complete remission, 36 participants on low-dose Voclosporin and 22 participants on high-dose Voclosporin achieved this, compared to 15 participants on placebo.
Voclosporin in Lupus Nephritis (AURORA Study)
Another study, AURORA (NCT03021499), also investigated Voclosporin in lupus nephritis. Key findings included:
- Voclosporin led to a greater average reduction in urine protein-creatinine ratio (UPCR) from baseline, with a mean reduction of approximately 2.7 mg/mg, compared to about 1.5 mg/mg for placebo. A lower UPCR indicates improved kidney function.
- The median time to achieve a 50% reduction in UPCR was significantly shorter for Voclosporin at 29 days, compared to 63 days for placebo.
- The median time to achieve a UPCR of ≤0.5 mg/mg was 169 days for Voclosporin, compared to 372 days for placebo.
Voclosporin in Lupus Nephritis (Early Protein Reduction Study)
A smaller study (NCT02949973) on Voclosporin in combination with standard of care for lupus nephritis showed that 7 participants achieved complete remission at Week 24, and 4 participants achieved complete remission at Week 48. Seven participants also showed a reduction or normalization of their urine protein/creatinine ratio (UPCR).
Currently Recruiting Trials
Researchers are actively seeking participants for several clinical trials investigating Voclosporin, an important medication for conditions like lupus nephritis. These studies aim to gather more information on its safety, efficacy, and potential in combination therapies.
One ongoing study, NCT07053891, is a survey focused on the real-world use of LUPKYNIS (Voclosporin) in patients with lupus nephritis. This study, sponsored by Otsuka Pharmaceutical Co., Ltd., is not assigned a specific phase and plans to enroll 400 participants to collect data on safety and efficacy under actual use conditions.
Another trial, known as the "Synergy Trial" (NCT07225387), is a Phase 4 study sponsored by NephroNet, Inc. It aims to enroll 30 participants with proliferative lupus nephritis. This trial investigates whether combining Belimumab and Voclosporin with background therapy (Mycophenolate Mofetil, MMF) can improve the proportion of patients achieving a complete renal response. Participants will be randomized into two arms: one with early MMF termination after 90 days and another with extended MMF for 360 days.
Qilu Pharmaceutical Co., Ltd. is sponsoring a Phase 3 study, NCT06406205, which seeks to enroll 270 subjects with active lupus nephritis. This trial will assess the efficacy of Voclosporin (referred to as QL1074) compared to a placebo in achieving renal response after 52 weeks of therapy.
Where to Participate
Clinical trials for Voclosporin are currently recruiting participants across several locations in the United States. There are 6 sites spread across 6 cities in 5 different states, providing opportunities for patients to engage in this important research.
Top locations for participation include:
- Lawrenceville, Georgia (2 sites)
- Glendale, Arizona (1 site)
- Atlanta, Georgia (1 site)
- Columbus, Ohio (1 site)
- Oklahoma City, Oklahoma (1 site)
- Fort Worth, Texas (1 site)
Eligibility for these studies generally includes individuals between 15 and 80 years of age, of any gender. Healthy volunteers are not being recruited for these trials, but children are eligible to participate if they meet the specific study criteria.
Development Timeline
The clinical development of Voclosporin began on October 27, 2005, marking the start of a comprehensive research journey. Since then, a total of 23 clinical trials have been initiated, enrolling over 4,000 participants to investigate the drug's potential across various conditions. Aurinia Pharmaceuticals Inc. has been a primary driver, sponsoring 16 of these studies, with contributions from other institutions like Leiden University Medical Center, Lux Biosciences, Inc., and the National Institute of Allergy and Infectious Diseases (NIAID).
Early research initially explored Voclosporin for conditions such as IBS-C and hyperphosphatemia. Over time, the development pipeline significantly expanded, focusing heavily on kidney-related diseases. This expansion included studies for Keratoconjunctivitis Sicca, Pediatric Lupus Nephritis, Adolescent Lupus Nephritis, Focal Segmental Glomerulosclerosis, and various forms of immunosuppression and transplantation, including kidney diseases and renal transplantation. More recently, studies have also addressed Systemic Lupus Erythematosus, Covid19, and Dry Eye Syndrome.
The development has progressed through all major clinical phases, with 9 Phase 3 trials and 7 Phase 2 trials demonstrating a significant commitment to advanced research. The latest trial is projected to conclude on November 6, 2025, indicating ongoing efforts to further understand and optimize Voclosporin's therapeutic applications.