FDA approves obinutuzumab to reduce relapse risk in childhood-onset idiopathic nephrotic syndrome

Children with frequently relapsing or steroid-dependent idiopathic nephrotic syndrome (INS) now have an FDA-approved steroid-sparing option. On September 25, 2026, the FDA approved obinutuzumab (Gazyva; Genentech) to reduce the risk of relapse in adult and pediatric patients aged 2 years and older with frequently relapsing or steroid-dependent childhood-onset INS who are in complete remission.¹ In the phase 3 INShore trial, 95.5% of patients receiving obinutuzumab achieved sustained complete remission at week 52 vs 73.2% of those receiving mycophenolate mofetil (MMF).²

Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, called the agent "the first FDA-approved treatment option for idiopathic nephrotic syndrome in 70 years," adding that directly targeting B cells offers the possibility of lasting remission.¹

INShore trial design and obinutuzumab efficacy in FRNS and SDNS

INShore (NCT05627557) was a randomized, open-label phase 3 trial that enrolled 85 patients aged 2 to 25 years with frequently relapsing or steroid-dependent nephrotic syndrome in complete remission, defined as no edema and a urine protein-to-creatinine ratio of 0.2 g/g or less.² Patients were randomized 1:1 to intravenous obinutuzumab (1000 mg, or 20 mg/kg if <45 kg) on days 1, 15, 168, and 182, or MMF 1200 mg/m²/day (maximum 2 g/day) for 52 weeks; ongoing glucocorticoids were tapered.² Overall, 63.5% of participants were younger than 12 years, and 75.3% had received prior nonsteroid immunosuppressive therapy.²

The primary endpoint favored obinutuzumab (adjusted difference, 23.36%; P = .003).² Obinutuzumab also reduced the risk of relapse or death by 75% (HR, 0.25; P = .007), lowered cumulative glucocorticoid dose (weight-adjusted median difference, −8.86 mg/kg; P = .04), and was associated with fewer relapses through week 52 (4 vs 23; adjusted rate ratio, 0.07; P = .002).² Sustained remission at week 76 was numerically higher but not statistically significant (P = .14).²

Obinutuzumab safety profile in pediatric nephrotic syndrome

Adverse events were more frequent with obinutuzumab than MMF (95.5% vs 82.9%), as were grade 3 or higher events (25.0% vs 7.3%); infusion-related reactions occurred in 36.4% of the obinutuzumab group.² Labeling highlights risks of hepatitis B reactivation and progressive multifocal leukoencephalopathy, notes a potentially higher risk of severe infection vs MMF, and advises that live vaccines be given at least 28 days before treatment in INS.¹

Disease burden and steroid dependence in childhood INS

INS is the most common form of primary glomerular disease in children. Steroids remain the mainstay of therapy, but relapse rates exceed 70%, and steroid toxicity limits long-term use.¹ Andi Callaway, founder and president of The Nephrotic Syndrome Foundation, said patients have long faced unpredictable relapses, prolonged steroid exposure, and the threat of disease progression.¹

Obinutuzumab mechanism and prior approvals across kidney disease

Obinutuzumab is a humanized type II anti-CD20 monoclonal antibody with a glycoengineered Fc region.³ It was previously approved for chronic lymphocytic leukemia, follicular lymphoma, and active lupus nephritis.⁴ The FDA granted Breakthrough Therapy Designation and Priority Review for INS, and obinutuzumab is under FDA review for primary membranous nephropathy and systemic lupus erythematosus.¹

References

1. Genentech. FDA approves Gazyva for idiopathic nephrotic syndrome in patients aged 2 and older. News release. September 25, 2026. Accessed September 25, 2026. https://www.gene.com/media/statements/ps_092526

2. Hogan J, Greenbaum LA, Nozu K, et al. WCN26-7699 B-cell–targeted therapy for idiopathic nephrotic syndrome: results of the phase III, global, multicenter INShore trial assessing obinutuzumab vs mycophenolate mofetil. Kidney Int Rep. 2026;11(5):106510. doi:10.1016/j.ekir.2026.106510

3. Roche. Roche announces positive phase III results for Gazyva/Gazyvaro in primary membranous nephropathy. News release. February 16, 2026. Accessed September 25, 2026. https://www.roche.com/media/releases/med-cor-2026-02-16

4. Obinutuzumab looks favorable for childhood-onset idiopathic nephrotic syndrome. Renal & Urology News. November 2025. Accessed September 25, 2026. https://www.renalandurologynews.com/news/obinutuzumab-looks-favorable-for-childhood-onset-idiopathic-nephrotic-syndrome/