Voclosporin
Also known as: Cyclosporin analogue C, ISA-247, ISA247, Lupkynis, Voclosporin
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Summary
Voclosporin is an oral calcineurin‑inhibiting cyclic peptide approved for the treatment of adult lupus nephritis, a serious kidney manifestation of systemic lupus erythematosus. It is used in combination with mycophenolate mofetil and low‑dose glucocorticoids to improve renal outcomes and reduce disease activity.
Mechanism of Action
Voclosporin, a cyclosporin analogue, binds intracellular cyclophilin A, forming a complex that blocks the phosphatase activity of calcineurin. This prevents dephosphorylation of nuclear factor of activated T‑cells (NFAT), thereby suppressing transcription of interleukin‑2 and other cytokines that drive T‑cell activation and downstream inflammatory cascades implicated in lupus nephritis.
What the Research Shows
Clinical evidence for voclosporin centres on the phase 3 AURORA 1 trial, a double‑blind, randomised study of 357 adults with biopsy‑proven class III, IV or V lupus nephritis. Patients receiving voclosporin (23.7 mg twice daily) plus mycophenolate mofetil and tapered steroids achieved a complete renal response at 52 weeks in 41% of cases, versus 23% with placebo (odds ratio 2.65, p < 0.0001). Safety was comparable between groups, with serious adverse events in 21% of each arm and similar rates of pneumonia. Review articles published in 2023‑2024 cite voclosporin as one of the few recent FDA‑approved agents for lupus nephritis, highlighting its role alongside belimumab and anifrolumab, while noting limited pediatric data.
Reported Benefits
In the AURORA 1 trial, voclosporin significantly increased the proportion of patients attaining complete renal response, suggesting better control of proteinuria and preservation of kidney function compared with standard therapy alone. The safety profile was similar to placebo when added to mycophenolate and steroids, indicating that the drug can be integrated into existing regimens without markedly increasing overall adverse events.
Limitations of the Evidence
Evidence is currently limited to a single pivotal phase 3 trial; long‑term outcomes beyond one year remain under‑studied. Comparative data versus other immunosuppressants or biologics are lacking, and pediatric efficacy and safety have not been established in the cited literature. Real‑world effectiveness and cost‑access issues are also not addressed in the available abstracts.
Safety Considerations
Voclosporin’s adverse‑event profile in the trial was comparable to placebo, with serious events occurring in 21% of participants in each arm. Infections, particularly pneumonia, were the most common serious infection (≈4% in each group). No deaths were attributed to the study drug. Clinicians should monitor for infections and standard calcineurin‑inhibitor toxicities, adjusting therapy as needed.
How It Is Administered
Voclosporin is administered orally, typically as a twice‑daily tablet (23.7 mg per dose in the pivotal trial). It is prescribed in combination with mycophenolate mofetil and a rapidly tapered low‑dose glucocorticoid regimen. Formulations are oral tablets; no intravenous or other routes are reported.
Routes of Administration
Goals & Uses
- T-cell immunosuppressionImmunologyHigh
- IgA nephropathy (investigational)RenalLow
- Lupus nephritis remissionAutoimmune Renal DiseaseHigh
- Proteinuria reductionRenalHigh
- Podocyte stabilizationRenalModerate
- Lupus nephritis treatmentAutoimmune / RenalHigh
- Reduce systemic disease activityAutoimmune DiseaseModerate
Contraindications
- Live vaccinesVaccinationModerate
- Known hypersensitivity to voclosporin or cyclosporineAllergyHigh
- Active serious infectionsInfectiousHigh
- Hypersensitivity to voclosporin or cyclosporin analoguesAllergyHigh
- Severe uncontrolled hypertensionCardiovascularHigh
- Severe renal impairment or eGFR <45 mL/min/1.73m² at initiationRenalHigh
- Concurrent use of strong CYP3A4 inhibitorsDrug InteractionHigh
Adverse Effects
- HypertensionCardiovascularCommonHigh blood pressure
- HeadacheNeurologicCommonPain in the head or upper neck
- TremorNeurologicUncommonInvoluntary shaking
- Urinary tract infectionGenitourinaryCommon
- InfectionsImmunologicCommon
- HyperkalemiaElectrolyte ImbalanceCommon
- Nephrotoxicity / decreased eGFRRenalCommon
- NephrotoxicityRenalCommon
- HyperlipidemiaMetabolicUncommon
Drug Interactions
- RifampinModerate
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine)High
- KetoconazoleHigh
- Potassium-sparing diuretics / ACE inhibitors / ARBsModerate
- Moderate CYP3A4 inhibitors (e.g., fluconazole, diltiazem)Moderate
- Other calcineurin inhibitors (e.g., tacrolimus)High
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin)High
- Nephrotoxic agents (e.g., NSAIDs, aminoglycosides)Moderate
Population Constraints
- PregnancyReproductive SafetyRelative
- Pediatric patients (<18 years)AgeRelative
- LactationReproductiveRelative
- Patients with active or chronic serious infectionsInfectionRelative
- Severe hepatic impairmentOrgan ImpairmentRelative
- BreastfeedingReproductiveRelative
Regulatory Status
- European UnionApprovedApproved: Active lupus nephritisEMA approval 2022.
- United StatesApprovedApproved: Active lupus nephritisFDA approval 2021 (Lupkynis).
- United KingdomApprovedApproved: Active lupus nephritisMHRA approval 2022.
First FDA‑approved oral calcineurin inhibitor specifically indicated for lupus nephritis; later approved in the EU and UK.
Evidence & Sources
- Journal ArticleModerateGonzález-García A, Cusácovich I, Ruiz-Irastorza G2023-01-01T00:00:00.000000Z
- Journal ArticleModerateSiegel CH, Sammaritano LR2024-01-01T00:00:00.000000Z
- Journal ArticleModerateRovin BH, et al.2021-01-01T00:00:00.000000Z
- Journal ArticleModerateHoi A, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleModeratePennesi M, Benvenuto S2023-01-01T00:00:00.000000Z
- Journal ArticleModerateRoveta A, et al.2024-01-01T00:00:00.000000Z
Frequently Asked Questions
What condition is voclosporin approved to treat?
Voclosporin is FDA‑approved for adult patients with active lupus nephritis, a kidney inflammation caused by systemic lupus erythematosus.
How does voclosporin differ from cyclosporine?
Voclosporin is a structural analogue of cyclosporine that retains calcineurin inhibition but has been modified to improve potency and pharmacokinetics, leading to its specific approval for lupus nephritis.
Is voclosporin used alone or with other drugs?
Clinical trials used voclosporin together with mycophenolate mofetil and a low‑dose steroid taper; it is not typically prescribed as monotherapy for lupus nephritis.
What are the main safety concerns?
In trials, serious adverse events occurred at similar rates to placebo, with infections like pneumonia being the most frequent serious infection. Monitoring for infection and standard calcineurin‑inhibitor effects is advised.
Is voclosporin studied in children?
The cited literature does not provide pediatric trial data; current evidence and approval pertain to adult patients only.
What is Voclosporin?
Voclosporin is an oral calcineurin‑inhibiting cyclic peptide approved for the treatment of adult lupus nephritis, a serious kidney manifestation of systemic lupus erythematosus. It is used in combination with mycophenolate mofetil and low‑dose glucocorticoids to improve renal outcomes and reduce disease activity.
What is Voclosporin used for?
Voclosporin is educationally associated with: T-cell immunosuppression, IgA nephropathy (investigational), Lupus nephritis remission, Proteinuria reduction, Podocyte stabilization, Lupus nephritis treatment, Reduce systemic disease activity. Educational only — not medical advice.
How is Voclosporin administered?
Recorded routes of administration: Oral.
What are the potential side effects of Voclosporin?
Reported adverse effects include: Hypertension, Headache, Tremor, Urinary tract infection, Infections, Hyperkalemia, Nephrotoxicity / decreased eGFR, Nephrotoxicity, Hyperlipidemia. This list is not exhaustive — consult a qualified clinician.
Who should avoid Voclosporin?
Recorded contraindications: Live vaccines, Known hypersensitivity to voclosporin or cyclosporine, Active serious infections, Hypersensitivity to voclosporin or cyclosporin analogues, Severe uncontrolled hypertension, Severe renal impairment or eGFR <45 mL/min/1.73m² at initiation, Concurrent use of strong CYP3A4 inhibitors. Consult a qualified clinician before use.