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Indications: LUPKYNIS is indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis (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.

Superior results with LUPKYNIS vs standard of care alone—patients were 2.7x more likely to respond (OR: 2.7; 95% CI: 1.6, 4.3)1

Primary endpoint: complete renal response at Week 52

Primary efficacy endpoint

Significantly greater complete renal response rate with LUPKYNIS (P<0.001)1

The AURORA trial included a scheduled steroid taper from 20-25 mg/day at Week 1 to 2.5 mg/day by Week 161,2,a,b

  • Demonstrated efficacy even with a substantial steroid taper to low sustained doses (≤2.5 mg/day)1,c

Primary endpoint had strict criteria for complete renal response1:

  • UPCR of ≤0.5 mg/mg
  • eGFR ≥60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of >20% or no treatment- or disease-related eGFR-associated event at the time of assessment
  • Presence of sustained, low-dose steroids from Weeks 44-52d
  • No administration of rescue medications

The AURORA Phase 3 trial was a randomized, double-blind, placebo-controlled trial of LUPKYNIS 23.7 mg BID in combination with MMF (target 2 g/day) and corticosteroids (n=179) vs placebo BID in combination with MMF and corticosteroids (n=178) in adults with class III or IV (alone or in combination with class V) or class V lupus nephritis. Efficacy was established on the basis of complete renal response at Week 52. Key secondary endpoints included complete renal response at Week 24, partial renal response (50% reduction in UPCR from baseline) at Weeks 24 and 52, time to UPCR ≤0.5 mg/mg, and time to 50% reduction in UPCR.1,3

aInitial treatment with intravenous (IV) methylprednisolone on Day 1 and Day 2 at a dose of 500 mg/day (body weight ≥45 kg) or 250 mg/day (body weight <45 kg). The starting dose of oral prednisone was 20 mg/day for patients with a body weight of <45 kg and 25 mg/day for patients ≥45 kg. The dose of oral corticosteroid was tapered down to achieve a target dose of 2.5 mg/day by the end of Week 16. When clinically indicated, patients were allowed to be completely titrated off oral corticosteroids.1,2

bPatients with a lack of response were allowed one 4-week interval without dose reduction or 1 dose escalation to the previous dose for 2 weeks at any time during the study. Lack of response was defined as no or minimal change in UPCR per investigator judgment over 3 visits or deterioration in UPCR not meeting the criteria for withdrawal.2

cThe protocol required steroid taper to 2.5 mg/day of prednisone by Week 16.1

dPatients did not receive more than 10 mg prednisone for ≥3 consecutive days or for ≥7 days in total during Weeks 44-52.1

Secondary endpoints

Demonstrated significantly greater renal response vs control as early as Week 241-3,e

Complete renal response at Week 24

(OR: 2.2; 95% CI: 1.3, 3.7)

Complete renal response at Week 24

Partial renal response at Week 24
(50% reduction in UPCR from baseline)

(OR: 2.4; 95% CI: 1.6, 3.8)

Partial renal response at Week 24

ePrimary endpoint of complete renal response, as previously described, was assessed at Week 52.

Secondary endpoints

Reduced proteinuria 2x faster than standard of care alone1,f

Median time to UPCR ≤0.5 mg/mg1,2,g

Median time to UPCR ≤0.5 mg/mg

Median time to 50% UPCR reduction2

Median time to 50% UPCR reduction

fPrimary endpoint of complete renal response, as previously described, was assessed at Week 52.

gAll patients were followed for 4 weeks after the last visit at Week 52.2

In a post hoc analysis, LUPKYNIS demonstrated consistent efficacy across racial and ethnic subgroups4,h

The study was not powered to detect differences in the treatment effect between these subgroups; therefore, results from this post hoc analysis should be interpreted with caution

hPrimary endpoint of complete renal response, as previously described, was assessed at Week 52.

BID=twice daily; eGFR=estimated glomerular filtration rate; HR=hazard ratio; MMF=mycophenolate mofetil; NC=not calculated; OR=odds ratio; UPCR=urine protein/creatinine ratio.

References: 1. LUPKYNIS [package insert]. Rockville, MD: Aurinia Pharma U.S., Inc., 2021. 2. Aurinia Pharma U.S., Inc. Data on file. 3. Rovin BH, Teng YKO, Ginzler EM, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. Published online May 7, 2021. doi:10.1016/S0140-6736(21)00578-X. 4. Arriens C, Polyakova S, Adzerikho I, et al; AURORA Study Group. AURORA phase 3 study demonstrates voclosporin statistical superiority over standard of care in lupus nephritis. Presented at: EULAR European E-Congress of Rheumatology 2020; June 3-Sept 1, 2020.

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Indications

LUPKYNIS is indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis (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.

CONTRAINDICATIONS: 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 calcineurin inhibitors (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.

ADVERSE REACTIONS

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.

SPECIFIC POPULATIONS

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. If used in this population, reduce LUPKYNIS dose.

Hepatic Impairment: For mild or moderate hepatic impairment, reduce LUPKYNIS dose. Avoid use with severe hepatic impairment.

Please see Prescribing Information including Boxed Warning and Medication Guide for LUPKYNIS.

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.

CONTRAINDICATIONS: 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 calcineurin inhibitors (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.

ADVERSE REACTIONS

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.

SPECIFIC POPULATIONS

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. If used in this population, reduce LUPKYNIS dose.

Hepatic Impairment: For mild or moderate hepatic impairment, reduce LUPKYNIS dose. Avoid use with severe hepatic impairment.

Please see Prescribing Information including Boxed Warning and Medication Guide for LUPKYNIS.