Brand Name
Lupkynis
Generic Name
Voclosporin
View Brand Information FDA approval date: January 22, 2021
Classification: Calcineurin Inhibitor Immunosuppressant
Form: Capsule
What is Lupkynis (Voclosporin)?
LUPKYNIS is indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis . 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. LUPKYNIS is a calcineurin-inhibitor immunosuppressant indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis . 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.
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Related Clinical Trials
LUPKYNIS Drug-use Results Survey
Summary: The purpose of this study is to survey the safety of LUPKYNIS in patients with lupus nephritis under actual use conditions. In addition, information on efficacy will be collected.
A Double-Blind, Placebo-Controlled, Dose Escalation Study to Assess the Efficacy, Safety and Pharmacokinetics of Voclosporin in Adolescent and Pediatric Subjects With Lupus Nephritis
Summary: The purpose of this study is to assess the efficacy and safety of voclosporin compared to placebo in achieving renal response following 24 weeks of therapy in adolescent and pediatric subjects with active lupus nephritis (LN).
Related Latest Advances
Brand Information
LUPKYNIS (Voclosporin)
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
1INDICATIONS AND USAGE
LUPKYNIS is indicated in combination with a background immunosuppressive therapy regimen
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.
2DOSAGE FORMS AND STRENGTHS
Capsules: 7.9 mg (voclosporin) oval, pink/orange in color, imprinted on one side with VCS in white ink.
3CONTRAINDICATIONS
LUPKYNIS is contraindicated in:
- Patients concomitantly using strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) because these medications can significantly increase exposure to LUPKYNIS which may increase the risk of acute and/or chronic nephrotoxicity
- Patients with a history of serious or severe hypersensitivity reaction, including anaphylaxis, to LUPKYNIS or any of its excipients
4ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Lymphoma and Other Malignancies
- Serious Infections
- Nephrotoxicity due to LUPKYNIS and Drug Interactions
- Hypertension
- Neurotoxicity
- Hyperkalemia
- QTc Prolongation
- Hypersensitivity Reactions
- Immunizations
- Pure Red Cell Aplasia
4.1Clinical 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
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.
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.
4.1.1Specific 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
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.
4.2Postmarketing 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
- Nausea, vomiting
5OVERDOSAGE
Cases of accidental overdose have been reported with LUPKYNIS; symptoms may include tremor, headache, nausea and vomiting, infections, tachycardia, urticaria, lethargy, and increases in blood urea nitrogen, serum creatinine, and alanine aminotransferase levels.
No specific antidote to LUPKYNIS therapy is available. If overdose occurs, general supportive measures and symptomatic treatment should be conducted, including stopping treatment with LUPKYNIS and assessing blood urea nitrogen, serum creatinine, eGFR and alanine aminotransferase levels.
Consider contacting a poison center (1-800-222-1222) or medical toxicologist for advice and review of overdosage management recommendations.
6DESCRIPTION
LUPKYNIS (voclosporin) capsules, a calcineurin-inhibitor immunosuppressant, is available for administration as soft gelatin capsules containing 7.9 mg voclosporin per capsule. Inactive ingredients include alcohol, Vitamin E polyethylene glycol succinate (NF), polysorbate 40 (NF), medium-chain triglycerides (NF), gelatin, sorbitol, glycerin, iron oxide yellow, iron oxide red, titanium dioxide, and water.
Voclosporin (90 to 95%
Voclosporin has an empirical formula of C
7CLINICAL STUDIES
The safety and efficacy of LUPKYNIS were investigated in Study 1 (NCT03021499), a 52-week, randomized, double-blind, placebo-controlled trial in patients with a diagnosis of systemic lupus erythematosus and with International Society of Nephrology / Renal Pathology Society (ISN/RPS) biopsy-proven active Class III or IV LN (alone or in combination with Class V LN) or Class V LN. Patients with Class III or IV LN (alone or in combination with Class V LN) were required to have a urine protein to creatinine (UPCR) ratio of ≥1.5 mg/mg; patients with Class V LN were required to have a UPCR of ≥2 mg/mg.
A total of 357 patients with LN were randomized in a 1:1 ratio to receive either LUPKYNIS 23.7 mg twice daily or placebo.
Patients in both arms received background treatment with MMF and corticosteroids as follows:
- Oral MMF at a target dose of 2 g/day (1 g twice a day). (Patients not already receiving MMF were started on MMF 500 mg twice a day with escalation to MMF 1 g twice a day after the first week.) Dose increases up to 3 g/day were allowed.
- 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) followed by a reducing taper of oral corticosteroids [oral prednisone 25 mg/day (body weight ≥45 kg) or 20 mg/day (body weight <45 kg); tapered to achieve a target dose of 2.5 mg/day by Week 16].
Throughout the study, patients were prohibited from using immunosuppressants (other than MMF and hydroxychloroquine/chloroquine) and from changing/commencing angiotensin II receptor blockers (ARBs) or angiotensin converting enzyme (ACE) inhibitors.
Patients with baseline eGFR ≤45 mL/min/1.73 m
Dosage was adjusted based on eGFR and BP in a pre-defined dosage adjustment protocol. Dosage adjustments should follow the dosage recommendations
The median age of patients was 31 years (range 18 to 72). The proportion of women was 88%. Approximately 36.1% were White, 9.5% were Black, 30.5% were Asian, 1.1% were American Indian or Alaska Native, and 22.7% were multiple race or other. Approximately 32.5% were Hispanic or Latino.
The mean (SD) daily dose of voclosporin was 41.3 (±9.7) mg/day. The mean (SD) daily dose of MMF was 1.9 (±0.4) g/day; 9% received >2 but ≤3 g/day of MMF. The mean (SD) daily dose of IV methylprednisolone (on Day 1 was 495 (±90) mg/day and Day 2 was 487 (±55) mg/day). The mean (SD) starting oral corticosteroid dose (Day 3) was 22.8 (±4.8) mg/day; approximately 81% received ≤2.5 mg/day of oral corticosteroids at Week 16.
The distribution by kidney biopsy class was Class III or IV (60.8%), Class III or IV in combination with Class V (24.9%), and Class V (14.3%). Mean (SD) eGFR on entry was 91 (±30) mL/min/1.73 m
The primary efficacy endpoint was the proportion of patients achieving complete renal response at Week 52. Complete renal response was defined as follows (both must be met):
- UPCR of ≤0.5 mg/mg, and
- eGFR ≥60 mL/min/1.73 m
In order to be considered a responder, the patient must not have received more than 10 mg prednisone for ≥3 consecutive days or for ≥7 days in total during Weeks 44 through 52. Patients who received rescue medication or withdrew from the study were considered non-responders.
A higher proportion of patients in the LUPKYNIS arm than the placebo arm achieved complete renal response at Week 52 (Table 4).
A higher proportion of patients in the LUPKYNIS arm than the placebo arm achieved complete renal response at Week 24 (32.4% vs. 19.7%; odds ratio: 2.2; 95% CI: 1.3, 3.7). Time to UPCR of ≤0.5 mg/mg was shorter in the LUPKYNIS arm than the placebo arm (median time of 169 days vs. 372 days; hazard ratio: 2.0; 95% CI: 1.5, 2.7).
A 2-year extension study (NCT03597464) followed Study 1. After reconsenting, patients remained on blinded randomized treatment. From the LUPKYNIS arm, 116 patients (64.8%) and from the placebo arm, 100 patients (56.2%) agreed to continue treatment for up to a further 2 years. Over 52% of the 357 patients completed the study (LUPKYNIS 56.4%, placebo 47.8%); 51.4% of LUPKYNIS patients and 41.0% of placebo patients were still on study treatment at the end of study.
Among the 179 LUPKYNIS patients and 178 placebo patients who entered Study 1, 36 (20.1%) LUPKYNIS patients and 21 (11.8%) placebo patients were observed to achieve sustained complete renal response, where achieving sustained complete renal response is defined as achieving renal response at Month 12 and maintaining the renal response at each subsequent study visit through Month 36 (the end of the extension study). Thirty-nine (21.8%) LUPKYNIS subjects and 41 (23.0%) placebo subjects had missing data either at the end of the first year or by the end of the 2 year extension and therefore have an unknown status for sustained complete renal response.
8HOW SUPPLIED/STORAGE AND HANDLING
LUPKYNIS (voclosporin) capsules 7.9 mg are oval, pink/orange capsules, imprinted on one side with VCS in white ink, packed in cold-formed aluminum blisters, consisting of laminated backing and lidding materials that are thermo-sealed together. Four individual 3 × 5 blister strips are assembled into a cardboard wallet.
LUPKYNIS is available in:
- NDC 75626-001-01: Wallet containing 60 capsules
- NDC 75626-001-02: Carton containing three wallets (180 capsules)
LUPKYNIS is provided in child-proof packaging to avoid unintentional ingestion of study medication by children.
Store at controlled room temperature 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF) [See USP Controlled Room Temperature].
Do not put LUPKYNIS in another container. Keep capsules in their original packaging until ready to be taken.
9PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Administration
Advise patients to:
- Swallow LUPKYNIS capsules whole, and not to open, crush, or divide LUPKYNIS capsules.
- Take LUPKYNIS on an empty stomach consistently as close to a 12-hour schedule as possible, and with a minimum of 8 hours between doses.
- If a dose is missed, take it as soon as possible within 4 hours after missing the dose. Beyond the 4-hour time frame, wait until the usual scheduled time to take the next regular dose. Do not double the next dose.
- Avoid eating grapefruit or drinking grapefruit juice while taking LUPKYNIS.
Development of Lymphoma and Other Malignancies
Inform patients that they are at an increased risk of developing lymphomas and other malignancies, particularly of the skin, due to immunosuppression. Advise patients to limit exposure to sunlight and ultraviolet (UV) light by wearing protective clothing and use a sunscreen with a high protection factor
Increased Risk of Infection
Inform patients that they are at an increased risk of developing a variety of infections, including opportunistic infections, due to immunosuppression and to contact their physician if they develop any symptoms of infection such as fever, sweats or chills, cough or flu-like symptoms, muscle aches, or warm, red, painful areas on the skin
Nephrotoxicity (Acute and/or Chronic)
Inform patients that LUPKYNIS can have toxic effects on the kidney that should be monitored. Advise patients to attend all visits and complete all blood tests ordered by their medical team
Hypertension
Inform patients that LUPKYNIS can cause high blood pressure which may require treatment with antihypertensive therapy. Advise patients to monitor their blood pressure
Neurotoxicity
Inform patients that they are at risk of developing adverse neurologic effects including seizure, altered mental status, and tremor. Advise patients to contact their physician should they develop vision changes, delirium, or tremors
Hyperkalemia
Inform patients that LUPKYNIS can cause hyperkalemia. Monitoring of potassium levels may be necessary, especially with concomitant use of other drugs known to cause hyperkalemia
Drug Interactions
Advise patients to tell their healthcare provider when they start or stop taking any concomitant medications. Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) are contraindicated with LUPKYNIS, and other CYP3A4 enzyme modulating drugs can alter LUPKYNIS exposure
Pregnancy
Inform female patients of the potential risk to a fetus and to avoid use of LUPKYNIS during pregnancy. When LUPKYNIS is administered in combination with MMF, refer patients to the MMF medication guide. Advise females to inform their healthcare provider if they are pregnant or become pregnant
Lactation
Advise female patients to inform their healthcare provider if they are breastfeeding or intend to breastfeed while taking LUPKYNIS
Hypersensitivity Reactions
Inform patients of the potential risk of hypersensitivity reactions. Advise patients to stop taking LUPKYNIS and seek medical attention if signs or symptoms of a hypersensitivity reaction occur (such as swelling of face, lips, tongue, or throat; difficulty breathing or swallowing)
Immunizations
Inform patients that LUPKYNIS can interfere with the usual response to immunizations and that they should avoid live vaccines
10SPL MEDGUIDE SECTION
This Medication Guide has been approved by the U.S. Food and Drug Administration Issued: 10/2025
11PACKAGE LABEL PRINCIPAL DISPLAY PANEL SECTION
Wallet: 60 Capsules
NDC 75626-001-01
12PACKAGE LABEL PRINCIPAL DISPLAY PANEL SECTION
Carton: 180 Capsules
NDC 75626-001-02