Last updated Jan. 30, 2023, by Marisa Wexler, MS
Fact-checked by Joana Carvalho, PhD
What is Lupkynis for lupus nephritis?
Lupkynis (voclosporin) is an oral therapy approved to treat lupus nephritis, a severe complication of lupus characterized by kidney inflammation and damages. It is marketed by Aurinia Pharmaceuticals.
How does Lupkynis work?
Lupkynis works by blocking the activity of a protein called calcineurin. In T-cells, a type of immune cell, blocking calcineurin activity reduces its inflammatory activity. Meanwhile, blocking calcineurin in podocytes (kidney cells) helps stabilize the molecular scaffolding that gives kidney cells their structure. It’s thought that Lupkynis may reduce the severity of lupus nephritis by simultaneously reducing inflammation and stabilizing kidney cells.
Who can take Lupkynis?
The U.S. Food and Drug Administration (FDA) has approved Lupkynis, given in addition to background therapy with mycophenolate mofetil and corticosteroids, to treat adults with active lupus nephritis. The therapy received similar approvals in the EU and the U.K.
Who should not take Lupkynis?
Lupkynis should not be used by anyone with a known serious allergy to the medication or any of its components.
Additionally, it shouldn’t be used in combination with strong CYP3A4 inhibitors — a class of medicine that includes ketoconazole, itraconazole, and clarithromycin, which are used to treat certain infections.
Lupkynis has not been evaluated in combination with cyclophosphamide, an immune-suppressing medicine sometimes used in managing lupus. Thus, it’s not recommended that Lupkynis be used with cyclophosphamide.
Patients with severely reduced kidney function (specifically with an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or less) may be at increased risk of kidney toxicity associated with using Lupkynis. The therapy should only be used in these patients if the potential benefits outweigh the risks.
Those with a blood pressure higher than 165/105 or having a hypertensive emergency should not start treatment with Lupkynis.
How is Lupkynis administered?
Lupkynis is available in 7.9 mg capsules. The recommended starting dose is 23.7 mg taken by mouth, twice per day, as close to every 12 hours as possible. If a dose is missed, it can be taken within a four-hour window, otherwise patients are advised to wait until the next scheduled dose.
The therapy should be taken on an empty stomach and patients should avoid eating grapefruit or drinking grapefruit juice while on it because certain grapefruit components can interfere with Lupkynis’ function.
Kidney function and blood pressure should be monitored regularly after patients starts Lupkynis. If kidney function worsens, the dose may be lowered, may be paused, or the treatment may be discontinued, depending on the severity of the change. If blood pressure increases beyond 165/105 mmHg or a hypertensive emergency occurs, Lupkynis should be discontinued and treatment to control blood pressure should be initiated.
If a patient has not had a clear benefit of Lupkynis after 24 weeks (about six months) on it, it should be discontinued.
Lupkynis in clinical trials
After results from a Phase 2 trial called AURA-LV (NCT02141672) identified 23.7 mg twice daily as the optimal dose for Lupkynis, the effectiveness of this dose was evaluated in a Phase 3 clinical trial called AURORA (NCT03021499) and in its extension study, AURORA 2 (NCT03597464). Data from AURORA supported Lupkynis approvals.
AURORA trial
AURORA enrolled 357 adults with active lupus nephritis who were randomly assigned to take Lupkynis or a placebo, both given on top of standard therapy with mycophenolate mofetil and corticosteroids, for one year.
The study’s main goal was to assess the number of patients achieving a complete renal response, a composite measure that basically shows kidney function was within a normal range or at least stable, without the need for a rescue medication or more than 10 mg of prednisone given over at least three consecutive days, or at least seven days total.
After one year, significantly more patients on Lupkynis than placebo were considered responders (40.8% vs. 22.5%). A higher proportion of Lupkynis-treated patients were considered partial responders after six and 12 months of treatment.
The therapy was also found to be generally well tolerated, with no new side effects reported. Infection was the most common side effect reported.
Ongoing trials
Aurinia has launched a Phase 3 clinical trial called VOCAL (NCT05288855) that aims to compare the efficacy and safety of Lupkynis against a placebo in 40 adolescents with lupus nephritis, ages 12–17. The study is being conducted at UNC-Chapel Hill in North Carolina. Participants are not yet being recruited.
Aurinia is also sponsoring an observational study (NCT05337124) that is collecting data on the effectiveness of Lupkynis in adults with lupus nephritis in the U.S.
Common side effects of Lupkynis
The most common side effects of Lupkynis include:
- reduced kidney function, kidney impairment, or acute kidney injury
- high blood pressure (hypertension)
- diarrhea
- headache
- anemia
- cough
- urinary tract infection
- abdominal pain
- hair loss (alopecia)
- ulcers in the mouth
- fatigue
- tremor
- decreased appetite
Kidney and nervous system toxicity
Lupkynis can cause acute and/or chronic kidney toxicity. Kidney function should be monitored and dosing should be reduced or stopped if kidney function deteriorates.
Lupkynis also can cause neurological problems like posterior reversible encephalopathy syndrome (PRES), which is characterized by headache, seizures, vision problems, and changes in mental status. Patients on Lupkynis should be monitored for neurological abnormalities, and if any are detected dosing should be reduced or stopped.
Hypertension
Lupkynis may increase the risk of high blood pressure, particularly if used in combination with other medications that can raise blood pressure. Blood pressure should be monitored in patients on Lupkynis, and if it gets dangerously high the therapy should be discontinued and appropriate care should be given to lower it.
Infections, cancers, and vaccines
Because Lupkynis works by lowering the activity of the immune system, it can reduce the body’s ability to fight off infections and eliminate abnormal cells. Patients on Lupkynis may be at an increased risk of developing certain infections and cancers, which can be serious. Monitoring and taking appropriate precautionary steps to minimize infection risk is recommended.
Vaccines that contain a live virus should not be administered to patients on Lupkynis. Additionally, since vaccines work by activating the immune system and Lupkynis works by blocking immune activity, vaccines may be less effective in patients on Lupkynis.
Potassium levels and heart abnormalities
Lupkynis may increase the risk of hyperkalemia — abnormally high levels of potassium — if it’s used in combination with other medicines that affect potassium levels. Potassium levels should be monitored where appropriate.
Lupkynis may also alter heart rhythm. Monitoring is recommended for patients known to be at risk for heart problems.
Pure red cell aplasia
Pure red cell aplasia, a condition where the body stops producing red blood cells that carry oxygen through the blood, has been reported in patients treated with other medicines that work through the same mechanism as Lupkynis. If this complication develops, it’s recommended that patients discontinue Lupkynis.
Use in pregnancy and breastfeeding
Lupkynis is not recommended for use during pregnancy or breastfeeding. In animal studies, the therapy was found to be toxic during pregnancy and to pass on to milk.
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