Equillium, Inc. announced that data from the Type B portion of the EQUALISE study in lupus nephritis patients was presented at the annual meeting of the American Society of Nephrology (ASN). The data highlights that subjects had high complete and partial response rates with rapid and deep reduction in urine protein creatinine ratio (UPCR) when itolizumab was added to mycophenolate mofetil (MMF) and corticosteroids. The Type B portion of the EQUALISE study in patients with active proliferative LN (apLN) is evaluating the safety, tolerability and clinical activity of subcutaneous delivery of itolizumab.

Patients must present with greater than 1 gram of proteinuria and have a recent kidney biopsy showing ISN/RPS class III or IV apLN to be eligible for the study. During the 24-week treatment period, patients receive a subcutaneous dose of 1.6 mg/kg every two weeks, with follow up out to 36 weeks. Consistent with standard of care, patients on study also receive 2-3 g/day of mycophenolate mofetil/mycophenolic acid (MMF/MPA), and patients may receive pulse systemic corticosteroids that are rapidly tapered.

A total of 17 subjects have been enrolled in the study, with 15 subjects reaching Week 28 (4 weeks following the final dose, or the end of study (EOS)). Based on published guidelines for the management of lupus nephritis from the European League Against Rheumatism (EULAR) and European Renal Association-European Dialysis and Transplant Association (ERA-EDTA), clinical activity assessments in this study are focused on the change in UPCR from baseline; proportion of apLN subjects with a complete response (CR), defined as 50% or greater reduction in UPCR and less than 0.5-0.7 g/g; and proportion of subjects achieving a partial response (PR), defined as 50% or greater reduction in UPCR. Key findings from analysis of the Type B portion of the EQUALISE study in lupus nephritis: Subjects were highly proteinuric: baseline mean UPCR of 4.9 g/g, Percent reduction from baseline in median spot UPCR is ~73%, Clinically meaningful responses were observed: By week 28 (EOS): 6 of 15 (40%) subjects achieved CR (UPCR < 0.7 g/g), Additional 5 of 15 (33%) subjects achieved PR (UPCR > 50% reduction).

There was a greater overall response rate (ORR) achieved in patients receiving itolizumab by 12 and 28 weeks than expected compared to the ORR in patients receiving standard of care alone using data generated from the Accelerating Medicines Partnership® (AMP) Lupus Network. Results are comparable to those observed in the Phase 3 AURORA1 study of voclosporin (ORR 70% at 6 and 12 months in active treatment). Consistent with the decline in UPCR overtime, subjects were able to taper their systemic corticosteroids over the course of the study.

Itolizumab induced consistent pharmacodynamic responses in patients reducing the levels of cell surface CD6 on T cells, which is known to reduce T cell activity. Itolizumab treatment (over 6 months) was also associated with reductions in absolute lymphocyte counts (ALC), another known pharmacodynamic effect. As noted in other studies of drugs whose mechanism leads to reductions in ALC, such as the S1P modulators, the reduction in ALC observed here was not associated with increased rates of infection or other adverse clinical signals.

77% of TEAEs were assessed as mild (Grade 1) or moderate (Grade 2) by the investigators. Two subjects had at least one serious adverse event.