LUPKYNIS

WARNING: MALIGNANCIES AND SERIOUS INFECTIONS Increased risk for developing malignancies and serious infections with LUPKYNIS or other immunosuppressants that may lead to hospitalization or death [see Warnings and Precautions ( 5.1 , 5.2 )]. WARNING: MALIGNANCIES AND SERIOUS INFECTIONS See full prescribing information for complete boxed warning. Increased risk for developing serious infections and malignancies with LUPKYNIS or other immunosuppressants that may lead to hospitalization or death. ( 5.1 , 5.2 )

5 WARNINGS AND PRECAUTIONS Nephrotoxicity (acute and/or chronic): May occur due to LUPKYNIS or concomitant nephrotoxic drugs. Monitor renal function; consider dosage reduction. ( 5.3 ) Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. ( 5.4 ) Neurotoxicity: Including risk of posterior reversible encephalopathy syndrome (PRES); monitor for neurologic abnormalities; reduce dosage or discontinue LUPKYNIS. ( 5.5 ) Hyperkalemia: Risk may be increased with other agents associated with hyperkalemia; monitor serum potassium levels. ( 5.6 ) QT Prolongation: Consider obtaining electrocardiograms and monitoring electrolytes in patients at high risk. ( 5.7 ) Hypersensitivity Reactions: Discontinue LUPKYNIS; treat and monitor until signs and symptoms resolve. ( 5.8 ) Immunizations: Avoid live vaccines. ( 5.9 ) Pure Red Cell Aplasia: Consider discontinuation. ( 5.10 ) 5.1 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 the intensity and duration of immunosuppression rather than to the use of any specific agent. Examine patients for skin changes and advise to avoid or limit sun exposure and to avoid artificial UV light (tanning beds, sun lamps) by wearing protective clothing and using a broad spectrum sunscreen with a high protection factor (SPF 30 or higher). 5.2 Serious Infections Immunosuppressants, including LUPKYNIS, increase the risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections. These infections may lead to serious, including fatal, outcomes. Viral infections reported include cytomegalovirus and herpes zoster infections. Monitor for the development of infection. Consider the benefits and risks for the individual patient; use the lowest effective dose needed to maintain response. 5.3 Nephrotoxicity LUPKYNIS, like other calcineurin-inhibitors, can cause acute and/or chronic nephrotoxicity. Nephrotoxicity was reported in clinical trials [see Adverse Reactions ( 6.1 )] . Monitor eGFR regularly during treatment, and consider dose reduction or discontinuation in patients with decreases in eGFR from baseline [see Dosage and Administration ( 2.3 )] ; persistent decrease of eGFR should be evaluated for chronic calcineurin-inhibitor nephrotoxicity. Consider the risks and benefits of LUPKYNIS treatment in light of the patient’s treatment response and risk of worsening nephrotoxicity, including co-administration with drugs associated with nephrotoxicity. The risk for acute and/or chronic nephrotoxicity is increased when LUPKYNIS is concomitantly administered with drugs associated with nephrotoxicity. 5.4 Hypertension Hypertension is a common adverse reaction of LUPKYNIS therapy and may require antihypertensive therapy [see Adverse Reactions ( 6.1 )] . Some antihypertensive drugs can increase the risk for hyperkalemia [see Warnings and Precautions ( 5.6 )] . Certain calcium-channel blocking agents (verapamil and diltiazem) may increase voclosporin blood concentrations and require dosage reduction of LUPKYNIS [see Dosage and Administration ( 2.5 ) and Drug Interactions ( 7.2 )] . Monitor blood pressure regularly during treatment and treat new-onset hypertension and exacerbations of pre-existing hypertension. If a patient experiences increases in blood pressure that cannot be managed with dose reduction of LUPKYNIS or other appropriate medical intervention, consider discontinuation of LUPKYNIS [see Dosage and Administration ( 2.3 )] . 5.5 Neurotoxicity LUPKYNIS, like other calcineurin-inhibitors, may cause a spectrum of neurotoxicities [see Adverse Reactions ( 6.1 )] . The most severe neurotoxicities include posterior reversible encephalopathy syndrome (PRES), delirium, seizure, and coma; others include tremors, paresthesias, headache, mental status changes, and changes in motor and sensory functions. Monitor for neurologic symptoms and consider dosage reduction or discontinuation of LUPKYNIS if neurotoxicity occurs. 5.6 Hyperkalemia Hyperkalemia, which may be serious and require treatment, has been reported with calcineurin inhibitors including LUPKYNIS [see Adverse Reactions ( 6.1 )] . Concomitant use of agents associated with hyperkalemia (e.g., potassium-sparing diuretics, ACE inhibitors, angiotensin receptor blockers) may increase the risk for hyperkalemia. Monitor serum potassium levels periodically during treatment. 5.7 QTc Prolongation LUPKYNIS prolongs the QTc interval in a dose-dependent manner after single dose administration at a dose higher than the recommended lupus nephritis therapeutic dose [see Clinical Pharmacology ( 12.2 )] . The use of LUPKYNIS in combination with other drugs that are known to prolong QTc may result in clinically significant QT prolongation. Certain circumstances may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including (1) bradycardia; (2) hypokalemia or hypomagnesemia; (3) concomitant use of other drugs that prolong the QTc interval; and (4) presence of congenital prolongation of the QT interval. 5.8 Hypersensitivity Reactions Postmarketing cases of hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with LUPKYNIS. If signs or symptoms of a hypersensitivity reaction occur, discontinue LUPKYNIS; treat and monitor until signs and symptoms resolve [see Contraindications ( 4 )] . 5.9 Immunizations Avoid the use of live attenuated vaccines during treatment with LUPKYNIS (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines). Inactivated vaccines noted to be safe for administration may not be sufficiently immunogenic during treatment with LUPKYNIS. 5.10 Pure Red Cell Aplasia Cases of pure red cell aplasia (PRCA) have been reported in patients treated with another calcineurin-inhibitor immunosuppressant. All of these patients reported risk factors for PRCA such as parvovirus B19 infection, underlying disease, or concomitant medications associated with PRCA. A mechanism for calcineurin-inhibitor-induced PRCA has not been elucidated. If PRCA is diagnosed, consider discontinuation of LUPKYNIS.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Lymphoma and Other Malignancies [see Warnings and Precautions ( 5.1 )] Serious Infections [see Warnings and Precautions ( 5.2 )] Nephrotoxicity due to LUPKYNIS and Drug Interactions [see Warnings and Precautions ( 5.3 )] Hypertension [see Warnings and Precautions ( 5.4 )] Neurotoxicity [see Warnings and Precautions ( 5.5 )] Hyperkalemia [see Warnings and Precautions ( 5.6 )] QTc Prolongation [see Warnings and Precautions ( 5.7 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.8 )] Immunizations [see Warnings and Precautions ( 5.9 ) ] Pure Red Cell Aplasia [see Warnings and Precautions ( 5.10 )] The most commonly reported 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurinia Pharmaceuticals at 1-833-672-0028 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 355 patients with LN were treated with voclosporin in the Phase 2 and 3 clinical studies with 224 exposed for at least 48 weeks, and 92 exposed for 3 years. Patients in Study 1 were randomized to LUPKYNIS 23.7 mg twice a day or placebo. A proportion of patients (n=216, 60%) in Study 1 continued in Study 1 extension, a double-blinded continuation study, and these patients were observed for up to 2 additional years [see Clinical Studies ( 14 )] . Patients in Study 2 were randomized to LUPKYNIS 23.7 mg twice a day, voclosporin 39.5 mg twice a day, or placebo. Patients received background treatment with MMF 2 g daily and an IV bolus of corticosteroids followed by a pre-specified oral corticosteroid taper dosing schedule; LUPKYNIS dosing was adjusted based on eGFR and BP. A total of 267 patients received at least 1 dose of LUPKYNIS 23.7 mg twice a day with 184 exposed for at least 48 weeks. A total of 88 patients received at least 1 dose of voclosporin 39.5 mg twice a day with 40 exposed for 48 weeks. Table 1 lists common adverse reactions occurring in at least 3% of patients receiving LUPKYNIS and at an incidence at least 2% greater than placebo in Studies 1 and 2. Table 1: Adverse Reactions in ≥3% of Patients Treated with LUPKYNIS 23.7 mg Twice a Day and ≥2% Higher than Placebo in Studies 1 and 2 Adverse Reaction LUPKYNIS 23.7 mg twice a day (n=267) Placebo (n=266) Glomerular filtration rate decreased See Specific Adverse Reactions below (Nephrotoxicity) 26% 9% Hypertension 19% 9% Diarrhea 19% 13% Headache 15% 8% Anemia 12% 6% Cough 11% 2% Urinary tract infection 10% 6% Abdominal pain upper 7% 2% Dyspepsia 6% 3% Alopecia 6% 3% Renal Impairment 6% 3% Abdominal pain 5% 2% Mouth ulceration 4% 1% Fatigue 4% 1% Tremor 3% 1% Acute kidney injury 3% 1% Decreased appetite 3% 1% Other adverse reactions reported in less than 3% of patients in the LUPKYNIS 23.7 mg group and at a 2% higher rate than in the placebo group through 48/52 weeks included gingivitis and hypertrichosis. The overall profile of adverse events seen in Study 1 extension (representing 203 patient-years of additional exposure) were similar in both nature and severity to those seen in the first year of treatment (Study 1). The annual incidence of adverse reactions reduced each successive year in both treatment groups. The integrated LN dataset is presented in the Specific Adverse Reactions section: Placebo-controlled Studies: Studies 1 and 2 were integrated to represent safety through 48/52 weeks for placebo (n=266), LUPKYNIS 23.7 mg twice a day (n=267), and voclosporin 39.5 mg twice a day (n=88). Among patients from Study 1, 100 patients (56.2%) on placebo twice a day and 116 patients (64.8%) on LUPKYNIS 23.7 mg twice a day continued in a follow-on study period for up to 2 additional years (Study 1 extension), with safety assessments through a total of up to 3 years. Exposure adjusted incidence rates were adjusted by study for all the adverse events reported in this section. Specific Adverse Reactions Infections In the integrated Study 1 and Study 2 data sets, infections were reported in 146 patients (107.4 per 100 patient-years) treated with placebo, 166 patients (135.2 per 100 patient-years) treated with LUPKYNIS 23.7 mg, and 58 patients (167.5 per 100 patient-years) treated with voclosporin 39.5 mg twice a day. The most frequent infections were upper respiratory tract infections, urinary tract infections, viral upper respiratory tract infections, and herpes zoster. Serious infections were reported in 27 patients (12.0 per 100 patient-years) treated with placebo, 27 patients (11.9 per 100 patient-years) treated with LUPKYNIS 23.7 mg, and 10 patients (14.4 per 100 patient-years) treated with voclosporin 39.5 mg twice a day. The most frequent serious infections were pneumonia, gastroenteritis, and urinary tract infections. Opportunistic infections were reported in 2 patients (0.9 per 100 patient-years) treated with placebo, 3 patients (1.3 per 100 patient-years) treated with LUPKYNIS 23.7 mg, and 1 patient (1.4 per 100 patient-years) treated with voclosporin 39.5 mg twice a day. The most frequent opportunistic infections were cytomegalovirus chorioretinitis, cytomegalovirus infection, and herpes zoster cutaneous disseminated. In Study 1 extension, infections and infestations were reported in 43 patients (32.3 per 100 patient-years) treated with placebo and 57 patients (41.4 per 100 patient-years) treated with LUPKYNIS 23.7 mg. There were 8 serious infections reported in both placebo treated patients (4.5 per 100 patient-years) and LUPKYNIS treated patients (3.9 per 100 patient-years). Nephrotoxicity In the integrated Study 1 and Study 2 data sets, glomerular filtration rate decreased was the most frequently reported adverse reaction, reported in 25 patients (11.3 per 100 patient-years) treated with placebo, 70 patients (37.1 per 100 patient-years) treated with LUPKYNIS 23.7 mg, and 27 patients (48.7 per 100 patient-years) treated with voclosporin 39.5 mg twice a day. In patients treated with LUPKYNIS 23.7 mg twice a day, decreases in glomerular filtration rate occurred within the first 3 months of LUPKYNIS treatment in 50/70 (71%), with 39/50 (78%) resolved or improved following dose modification, and of those 25/39 (64%) resolved or improved within 1 month [see Dosage and Administration ( 2.3 )] . Decreases in glomerular filtration rate resulted in permanent discontinuation of LUPKYNIS in 10/70 (14%), and resolved in 4/10 (40%) 3 months after treatment discontinuation. Renal adverse reactions (defined as renal impairment, acute kidney injury, blood creatinine increased, azotemia, renal failure, oliguria, and proteinuria) were reported in 22 patients (9.5 per 100 patient-years) treated with placebo, 26 patients (11.3 per 100 patient-years) treated with LUPKYNIS 23.7 mg, and 11 patients (16.5 per 100 patient-years) treated with voclosporin 39.5 mg twice a day. Serious renal adverse reactions were reported in 9 patients (3.7 per 100 patient-years) treated with placebo, 13 patients (5.6 per 100 patient-years) treated with LUPKYNIS 23.7 mg, and 0 patients (0 per 100 patient-years) treated with voclosporin 39.5 mg twice a day. The most frequent serious renal adverse reactions were acute kidney injury and renal impairment. In Study 1 extension, eGFR decreased was reported in 5 patients (2.8 per 100 patient-years) treated with placebo and 12 patients (6.1 per 100 patient-years) treated with LUPKYNIS 23.7 mg. Renal and urinary adverse events were reported in 10 patients (5.7 per 100 patient-years) treated with placebo and 21 patients (10.7 per 100 patient-years) treated with LUPKYNIS. Serious renal and urinary adverse events were reported in 5 patients (2.8 per 100 patient-years) treated with placebo and 2 patients (0.9 per 100 patient-years) treated with LUPKYNIS, and included lupus nephritis in both treatment groups. Hypertension In the integrated Study 1 and Study 2 data sets, hypertension was reported in 23 patients (10.3 per 100 patient-years) treated with placebo, 51 patients (25.2 per 100 patient-years) treated with LUPKYNIS 23.7 mg, and 16 patients (26.0 per 100 patient-years) treated with voclosporin 39.5 mg twice a day. Serious hypertension was reported in 1 patient (0.4 per 100 patient-years) treated with placebo, 5 patients (2.1 per 100 patient-years) treated with LUPKYNIS 23.7 mg, and 2 patients (2.8 per 100 patient-years) treated with voclosporin 39.5 mg twice a day. In Study 1 extension, hypertension was reported in 7 patients (4.0 per 100 patient-years) treated with placebo and 10 patients (4.9 per 100 patient-years) treated with LUPKYNIS 23.7 mg. Neurotoxicity In the integrated Study 1 and Study 2 data sets, nervous system disorders were reported in 44 patients (21.6 per 100 patient-years) treated with placebo, 74 patients (38.9 per 100 patient-years) treated with LUPKYNIS 23.7 mg, and 24 patients (42.5 per 100 patient-years) treated with voclosporin 39.5 mg twice a day. The most frequent neurological adverse reactions were headache, tremor, dizziness, post herpetic neuralgia, migraine, paresthesia, hypoaesthesia, seizure, tension headache, and disturbance in attention. Serious nervous system disorders were reported in 2 patients (0.9 per 100 patient-years) treated with placebo, 9 patients (3.9 per 100 patient-years) treated with LUPKYNIS 23.7 mg, and 3 patients (4.3 per 100 patient-years) treated with voclosporin 39.5 mg twice a day. The most frequent serious neurological adverse reactions were headache, migraine, seizure, and posterior reversible encephalopathy syndrome. In Study 1 extension, nervous system disorders (including headache) were reported in 8 patients (4.7 per 100 patient-years) treated with placebo and 14 patients (7.3 per 100 patient-years) treated with LUPKYNIS 23.7 mg. Malignancy In the integrated Study 1 and Study 2 data sets, malignancies were reported in 0 patients (0 per 100 patient-years) treated with placebo, 4 patients (1.7 per 100 patient-years) treated with LUPKYNIS 23.7 mg, and 0 patients (0 per 100 patient-years) treated with voclosporin 39.5 mg twice a day. These consisted of single occurrences of stage 0 cervical carcinoma, skin neoplasm, pyoderma gangrenosum, and breast tumor excision. In Study 1 extension, there were no reports of malignancies in either treatment arm. Hyperkalemia In the integrated Study 1 and Study 2 data sets, hyperkalemia was reported in 2 patients (0.8 per 100 patient-years) treated with placebo, 5 patients (2.1 per 100 patient-years) treated with LUPKYNIS 23.7 mg, and 1 patient (1.4 per 100 patient-years) treated with voclosporin 39.5 mg twice a day. In Study 1 extension, hyperkalemia was reported in 0 patients treated with placebo and 1 patient (0.5 per 100 patient-years) treated with LUPKYNIS 23.7 mg. QT Prolongation In the integrated Study 1 and Study 2 data sets, QT prolongation was reported in 0 patients (0 per 100 patient-years) treated with placebo, 2 patients (0.9 per 100 patient-years) treated with LUPKYNIS 23.7 mg, and 1 patient (1.4 per 100 patient-years) treated with voclosporin 39.5 mg twice a day. In Study 1 extension, no patient treated with LUPKYNIS 23.7 mg reported QT prolongation. 6.2 Postmarketing Experience The following adverse recations have been identified during post approval use of LUPKYNIS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Hypersensitivity reactions, including anaphylaxis and angioedema [see Warnings and Precautions ( 5.8 )] Nausea, vomiting

<table cellpadding="3" frame="border" rules="all" width="100%"><caption>Table 1: Adverse Reactions in &#x2265;3% of Patients Treated with LUPKYNIS 23.7 mg Twice a Day and &#x2265;2% Higher than Placebo in Studies 1 and 2</caption><colgroup><col align="left"/><col align="center"/><col align="center"/></colgroup><tbody><tr><th align="center">Adverse Reaction</th><th>LUPKYNIS 23.7 mg twice a day (n=267) </th><th>Placebo (n=266) </th></tr><tr><td>Glomerular filtration rate decreased <footnote ID="tbl1fn1">See Specific Adverse Reactions below (Nephrotoxicity)</footnote></td><td>26%</td><td>9%</td></tr><tr><td>Hypertension</td><td>19%</td><td>9%</td></tr><tr><td>Diarrhea</td><td>19%</td><td>13%</td></tr><tr><td>Headache</td><td>15%</td><td>8%</td></tr><tr><td>Anemia</td><td>12%</td><td>6%</td></tr><tr><td>Cough</td><td>11%</td><td>2%</td></tr><tr><td>Urinary tract infection</td><td>10%</td><td>6%</td></tr><tr><td>Abdominal pain upper</td><td>7%</td><td>2%</td></tr><tr><td>Dyspepsia</td><td>6%</td><td>3%</td></tr><tr><td>Alopecia</td><td>6%</td><td>3%</td></tr><tr><td>Renal Impairment <footnoteRef IDREF="tbl1fn1"/></td><td>6%</td><td>3%</td></tr><tr><td>Abdominal pain</td><td>5%</td><td>2%</td></tr><tr><td>Mouth ulceration</td><td>4%</td><td>1%</td></tr><tr><td>Fatigue</td><td>4%</td><td>1%</td></tr><tr><td>Tremor</td><td>3%</td><td>1%</td></tr><tr><td>Acute kidney injury <footnoteRef IDREF="tbl1fn1"/></td><td>3%</td><td>1%</td></tr><tr><td>Decreased appetite</td><td>3%</td><td>1%</td></tr></tbody></table>