Obinutuzumab Efficacy, Safety for FSGS Treatment

Ladan Zand, MD, and others examined the efficacy and safety of obinutuzumab, a type II anti-CD20 antibody, to treat patients with focal segmental glomerulosclerosis (FSGS) who were treatment-resistant or dependent on immunosuppressive therapy. They reported findings in a poster presented at ASN Kidney Week 2024, titled Single-Center, Phase 2, Open-Label Trial Evaluating the Efficacy and Safety of Obinutuzumab in Treatment of Immunosuppression-Resistant Primary FSGS, or Contraindication to High-Dose Corticosteroids.

Study participants received two doses of 1 g obinutuzumab two weeks apart at baseline and six months. The primary outcome was the change in proteinuria from baseline to six and 12 months. Secondary endpoints included complete remission (proteinuria <0.3g/d) or partial remission (50% reduction in proteinuria and proteinuria <3.5 g/d) and rates of serious adverse events.

There were 20 patients in the study, and all had failed two to three prior therapies. The average age was 45.3±17.5 years and 55% were male. Systolic blood pressure was 132±17.5 mmHg and diastolic blood pressure was 77.1±9.5 mmHg.

Patients demonstrated a significant improvement in proteinuria, from 10.7 g/d (7.5-13.7) at baseline to 3.8 g/d (1.5-8.6)] at 12 months (P=.001). There were also significant improvements in serum albumin, cholesterol, and eGFR. At 12 months, eight patients (40%) achieved complete or partial remission, and none had a relapse. There were three serious adverse events, all of which were unrelated to obinutuzumab. Seven infusion-related adverse reactions and seven infections occurred, none of which resulted in hospitalization.

Overall, obinutuzumab significantly reduced proteinuria in patients with primary FSGS for whom two to three previous therapies had failed. “Reduction in proteinuria was associated with an improvement in eGFR and serum albumin with an acceptable side effect profile,” the authors said.

Source: Zand L, Greene EL, Cheungpasitporn W, Vargas-Brochero MJ, Machado M, Sethi S, Ronco PM, Fervenza FC. Single-center, phase 2, open-label trial evaluating the efficacy and safety of obinutuzumab in treatment of immunosuppression-resistant primary FSGS, or contraindication to high-dose corticosteroids. TH-PO1206. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2024; October 24, 2024; San Diego, California. Commercial support for the study was provided by Genentech.