- LUPKYNIS® achieved significantly earlier reductions in UPCR and significantly higher renal response rates in lupus nephritis patients with high proteinuria, compared to patients treated with mycophenolate mofetil and low-dose steroids alone, in a pooled, post-hoc analysis.1
- LUPKYNIS® was associated with a higher rate of renal secretion and lower overall exposure to kidney tissue, which may be associated with an improved safety profile, compared to cyclosporine and tacrolimus, in an animal study.2
- LUPKYNIS® did not inhibit the kidney tubular reabsorption of calcium and magnesium and therefore does not cause hypercalciuria or hypomagnesemia, in contrast to tacrolimus, in an animal study.3
Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH) (Aurinia or the Company) today announced three oral presentations at the Annual Meeting of the European Renal Association (ERA), providing additional support for the efficacy and safety of LUPKYNIS® (voclosporin), a next generation calcineurin inhibitor (CNI) approved in the U.S. and Europe for the treatment of adults with active lupus nephritis (LN).
One oral presentation included results of a post-hoc, pooled analysis of the Phase 2 AURA-LV (NCT02141672) and Phase 3 AURORA 1 (NCT03021499) studies showing that LUPKYNIS® taken with mycophenolate mofetil (MMF) and low-dose steroids resulted in significantly higher renal response rates and significantly earlier reductions in UPCR in LN patients with high proteinuria (≥2 mg/mg), compared to MMF and low-dose steroids alone.1 These findings are meaningful, as recent post-hoc analyses with monoclonal antibody therapies demonstrated limited efficacy in patients with LN and moderate to high proteinuria (UPCR ≥2 to ≥3 mg/mg), potentially due to an increase in renal antibody clearance.4-7
“Lupus nephritis is a common and serious manifestation of lupus and can lead to significant kidney damage without appropriate treatment. The findings presented at ERA this week show that voclosporin achieved a 50% proteinuria reduction at 28 days, compared to 57 days in the control arm (p<0.0001). Additionally, the median time to achieving a UPCR of ≤0.5 mg/mg was 211 days in the voclosporin arm, while less than 50% of patients in the control arm ever achieved this endpoint,” said Dr. Greg Keenan, Chief Medical Officer of Aurinia. “Additionally, in two pre-clinical animal models, voclosporin showed a higher rate of renal secretion, lower overall kidney exposure, and no associated hypercalciuria or hypomagnesemia, compared to the legacy, first-generation CNIs. These results are relevant, as they demonstrate important clinical and mechanistic findings associated with voclosporin treatment.”
An oral presentation of a study assessing kidney tissue in mice treated with voclosporin (VCS), tacrolimus (TAC), and cyclosporine (CSA) revealed differential retention and distribution of these three therapies, consistent with their respective renal clearances in humans. Higher drug exposure and >90% renal reabsorption was observed for both CSA and TAC in this study, whereas the renal handling of VCS suggested a significant component of tubular secretion. The higher rate of secretion and lower overall exposure of kidney tissue to VCS may be associated with an improved safety profile when compared to the more diffuse distribution and greater renal retention of CSA and TAC.2
Another oral presentation compared the effects of TAC and VCS on calcium and magnesium levels in rats. Clinically, TAC frequently causes hypercalciuria and hypomagnesemia by inhibiting kidney tubular calcium and magnesium reabsorption. The study found that, unlike TAC, VCS does not inhibit the kidney tubular reabsorption of calcium and magnesium and therefore does not cause hypercalciuria or hypomagnesemia. The data showed that the tubulotoxicity observed with TAC is not apparent with VCS treatment at clinically relevant doses.3
About Lupus Nephritis
Lupus Nephritis is a serious manifestation of systemic lupus erythematosus (SLE), a chronic and complex autoimmune disease. About 200,000-300,000 people live with SLE in the U.S., and about one-third of these people are diagnosed with lupus nephritis at the time of their SLE diagnosis. About 50 percent of all people with SLE may develop lupus nephritis. If poorly controlled, lupus nephritis can lead to permanent and irreversible tissue damage within the kidney. Black and Asian people with SLE are four times more likely to develop lupus nephritis and Hispanic people are approximately twice as likely to develop the disease compared to White people with SLE. Black and Hispanic people with SLE also tend to develop lupus nephritis earlier and have worse outcomes, compared to White people with SLE.
LUPKYNIS® is the first U.S. FDA- and EC-approved oral medicine for the treatment of adult patients with active LN. LUPKYNIS is a novel, structurally modified calcineurin inhibitor (CNI) with a dual mechanism of action, acting as an immunosuppressant through inhibition of T-cell activation and cytokine production and promoting podocyte stability in the kidney. The recommended starting dose of LUPKYNIS is three capsules twice daily with no requirement for serum drug monitoring. Dose modifications can be made based on Aurinia’s proprietary personalized eGFR-based dosing protocol. Boxed Warning, warnings, and precautions for LUPKYNIS are consistent with those of other CNI-immunosuppressive treatments.
Aurinia Pharmaceuticals is a fully integrated biopharmaceutical company focused on delivering therapies to treat targeted patient populations with high unmet medical needs that are impacted by autoimmune, kidney and rare diseases. In January 2021, the Company introduced LUPKYNIS® (voclosporin), the first FDA-approved oral therapy dedicated to the treatment of adult patients with active lupus nephritis. The Company’s head office is in Edmonton, Alberta, and its U.S. commercial office is in Rockville, Maryland. The Company focuses its development efforts globally.
INDICATION AND IMPORTANT SAFETY INFORMATION
LUPKYNIS is indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active LN. Limitations of Use: Safety and efficacy of LUPKYNIS have not been established in combination with cyclophosphamide. Use of LUPKYNIS is not recommended in this situation.
IMPORTANT SAFETY INFORMATION
BOXED WARNINGS: MALIGNANCIES AND SERIOUS INFECTIONS
Increased risk for developing malignancies and serious infections with LUPKYNIS or other immunosuppressants that may lead to hospitalization or death.
LUPKYNIS is contraindicated in patients taking strong CYP3A4 inhibitors because of the increased risk of acute and/or chronic nephrotoxicity, and in patients who have had a serious/severe hypersensitivity reaction to LUPKYNIS or its excipients.
WARNINGS AND PRECAUTIONS
Lymphoma and Other Malignancies: Immunosuppressants, including LUPKYNIS, increase the risk of developing lymphomas and other malignancies, particularly of the skin. The risk appears to be related to increasing doses and duration of immunosuppression rather than to the use of any specific agent.
Serious Infections: Immunosuppressants, including LUPKYNIS, increase the risk of developing bacterial, viral, fungal, and protozoal infections (including opportunistic infections), which may lead to serious, including fatal, outcomes.
Nephrotoxicity: LUPKYNIS, like other CNIs, may cause acute and/or chronic nephrotoxicity. The risk is increased when CNIs are concomitantly administered with drugs associated with nephrotoxicity.
Hypertension: Hypertension is a common adverse reaction of LUPKYNIS therapy and may require antihypertensive therapy.
Neurotoxicity: LUPKYNIS, like other CNIs, may cause a spectrum of neurotoxicities: severe include posterior reversible encephalopathy syndrome (PRES), delirium, seizure, and coma; others include tremor, paresthesia, headache, and changes in mental status and/or motor and sensory functions.
Hyperkalemia: Hyperkalemia, which may be serious and require treatment, has been reported with CNIs, including LUPKYNIS. Concomitant use of agents associated with hyperkalemia may increase the risk for hyperkalemia.
QTc Prolongation: LUPKYNIS prolongs the QTc interval in a dose-dependent manner when dosed higher than the recommended lupus nephritis therapeutic dose. The use of LUPKYNIS in combination with other drugs that are known to prolong QTc may result in clinically significant QT prolongation.
Immunizations: Avoid the use of live attenuated vaccines during treatment with LUPKYNIS. Inactivated vaccines noted to be safe for administration may not be sufficiently immunogenic during treatment with LUPKYNIS.
Pure Red Cell Aplasia: Cases of pure red cell aplasia (PRCA) have been reported in patients treated with another CNI immunosuppressant. If PRCA is diagnosed, consider discontinuation of LUPKYNIS.
Drug-Drug Interactions: Avoid co-administration of LUPKYNIS and strong CYP3A4 inhibitors or with strong or moderate CYP3A4 inducers. Reduce LUPKYNIS dosage when co-administered with moderate CYP3A4 inhibitors. Reduce dosage of certain P-gp substrates with narrow therapeutic windows when co-administered.
The most common adverse reactions (>3%) were glomerular filtration rate decreased, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, abdominal pain upper, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, tremor, acute kidney injury, and decreased appetite.
Pregnancy/Lactation: May cause fetal harm. Advise not to breastfeed.
Renal Impairment: Not recommended in patients with baseline eGFR ≤45 mL/min/1.73 m2 unless benefit exceeds risk. Severe renal impairment: Reduce LUPKYNIS dose.
Mild and Moderate Hepatic Impairment: Reduce LUPKYNIS dose. Severe hepatic impairment: Avoid LUPKYNIS use.
- Almaani S et al. Efficacy and Safety of Voclosporin in Patients with Proteinuria ≥2 mg/mg: An Integrated Analysis of the AURA-LV and AURORA 1 Studies. Presented at the European Renal Associate Annual Meeting, 2023, Milan, Italy.
- Zhou S et al. Selective renal tissue disposition of the calcineurin inhibitors voclosporin, cyclosporine, and tacrolimus. Presented at the European Renal Associate Annual Meeting, 2023, Milan, Italy.
- Wei Ky et al. Tacrolimus but not voclosporin inhibits kidney tubular calcium and magnesium reabsorption in rats at clinically therapeutic doses. Presented at the European Renal Associate Annual Meeting, 2023, Milan, Italy.
- Furie RA et al. Ann Rheum Dis. 2022;81:100-107.
- Jayne D et al. Ann Rheum Dis. 2022;81(4):496-506.
- Liu T et al. Lupus. Apr 2022;31(4):424-432.
- Rovin BH et al. Kidney Int. Feb 2022;101(2):403-413.