Safety and efficacy of itolizumab in lupus nephritis: results from phase Ib EQUALISE study

Itolizumab is a first-in-class anti-CD6 monoclonal antibody that selectively targets the CD6-activated leukocyte cell adhesion molecule signaling pathway to suppress pathogenic T effector cells while maintaining T regulatory cells. Itolizumab has recently been evaluated in an open-label, proof-of-concept, phase Ib EQUALISE study, showing a favorable safety and tolerability profile in patients with lupus nephritis.

Topline results¹

• Out of 17 patients enrolled, 16 patients completing Week 36 were analyzed.
  • The baseline mean urine protein creatinine ratio (UPCR) was 4.9 g/g.
• The median spot UPCR showed a reduction of ~73% from the baseline.
• By Week 36, more than 80% of subjects achieved >50% reduction in UPCR (Figure 1)

Figure 1. Clinical response* 

CR, complete response; PR, partial response.
*Data from Businesswire.^1
†UPCR ≤0.7 g/g.
^‡UPCR ≥50% reduction.

• The overall response rate (ORR) achieved in patients receiving itolizumab by Week 12 and 28 were greater than the ORR in patients receiving standard-of-care alone. Additionally, the results were comparable with those from voclosporin in the phase III AURORA1 study (ORR 70% at Month 6 and 12 in active treatment).
• Patients were able to taper their systemic corticosteroids by >80% by Week 24.
• Itolizumab consistently reduced cell surface CD6 levels on T cells and was associated with reductions in absolute lymphocyte counts over a 6-month treatment period.
• Reduction in absolute lymphocyte counts was not associated with increased rates of infection or other adverse events.
• The majority of treatment-emergent adverse events were mild (Grade 1) or moderate (Grade 2) in severity. The two most common treatment-emergent adverse events were lymphopenia and peripheral edema. Two subjects had ≥1 serious adverse event, unrelated to study treatment.