What are the clinical uses and dosing guidelines for Voclosporin (Cyclosporin analog) in patients?

Clinical Uses and Dosing Guidelines for Voclosporin

Voclosporin is primarily indicated for the treatment of adults with active lupus nephritis (LN) in combination with mycophenolate mofetil (MMF) and low-dose glucocorticoids in patients with baseline eGFR of at least 45 mL/min/1.73 m². 1

Primary Indication and Patient Selection

• Approved for adults with active lupus nephritis (Class III, IV, or V alone or in combination)
• Patient eligibility criteria:
  • Confirmed diagnosis of systemic lupus erythematosus with lupus nephritis
  • Baseline eGFR ≥45 mL/min/1.73 m² 1, 2
  • Not recommended for patients with eGFR <45 mL/min/1.73 m² 1

Dosing Regimen

• Recommended dose: 23.7 mg twice daily 1, 2
• Always administered as part of combination therapy:
  • With mycophenolate mofetil (target dose 2 g/day)
  • With reduced steroid regimen 1
• No therapeutic drug monitoring required (unlike other calcineurin inhibitors) 3

Efficacy

• FDA approval based on positive results from:
  • Phase 2b AURA-LV trial
  • Phase 3 AURORA-1 trial 1
• Complete remission rates at 6 and 12 months significantly higher with voclosporin 1
• Long-term data from AURORA-2 showed:
  • Sustained efficacy with mean UPCR at 30 months of 0.58 mg/g in voclosporin arm vs 1.34 g/g in control arm 1
  • Complete renal response in 50.9% vs 39.0% of patients after 3 years of treatment 4

Monitoring and Safety Considerations

Renal Function

• Monitor eGFR closely, especially in first 3 months of treatment 1
• Decreases in GFR occurred within first 3 months in 71% of patients on voclosporin 23.7 mg 2
• Most GFR decreases (78%) resolved following dose modification 2

Infections

• Increased risk of infections (135.2 per 100 patient-years with voclosporin vs 107.4 with placebo) 2
• Most common: upper respiratory tract infections, urinary tract infections, viral upper respiratory infections, herpes zoster 2
• Monitor for opportunistic infections (cytomegalovirus, herpes zoster) 2

Hypertension

• Reported in 25.2 per 100 patient-years with voclosporin vs 10.3 with placebo 2
• Regular blood pressure monitoring recommended

Drug Interactions

• Strong CYP3A4 inhibitors (e.g., ketoconazole) significantly increase voclosporin exposure (18-fold increase in AUC) and should be avoided 2, 5
• Strong CYP3A4 inducers (e.g., rifampin) significantly decrease voclosporin exposure and should be avoided 2, 5
• P-glycoprotein inhibitors (e.g., verapamil) increase voclosporin exposure (2.7-fold increase in AUC) 5
• Voclosporin increases exposure of P-glycoprotein substrates (e.g., digoxin) 5

Special Populations

Renal Impairment

• Mild to moderate renal impairment: No dose adjustment needed 6
• Severe renal impairment: 1.5-fold increase in AUC; not recommended for patients with eGFR <45 mL/min/1.73 m² 1, 6

Hepatic Impairment

• Mild to moderate hepatic impairment: 1.5- to 2-fold increase in exposure; use with caution 6
• Effect of severe hepatic impairment unknown 2

Clinical Pearls

• Voclosporin has a more consistent pharmacokinetic-pharmacodynamic profile compared to other calcineurin inhibitors 3
• Benefit appears less pronounced in patients receiving MMF >2 g/day 1
• Reduction in proteinuria may be partly due to non-immunosuppressive effects (decreased glomerular filtration pressure, stabilization of podocyte cytoskeleton) 1
• Long-term data (3 years) shows maintained safety profile with reduced frequency of adverse events over time 4