The US FDA approved Roche/Genentech's Gazyva (obinutuzumab) to reduce the risk of relapse in adult and pediatric patients 2 years of age and older with frequently relapsing or steroid-dependent, childhood-onset idiopathic nephrotic syndrome (INS) who are in remission. The approval adds a new indication to a molecule previously cleared for certain cancers and for lupus nephritis in adults.
The INS approval received Breakthrough Therapy, Orphan Drug, and Priority Review designations in this predominantly pediatric population.
The pivotal INSHORE trial (NCT05627557) was a Phase III, randomized, controlled, open-label, multicenter study enrolling 85 patients aged 2 years and older with childhood-onset frequently relapsing or steroid-dependent INS who were in complete remission at entry. Patients received intravenous obinutuzumab dosed by weight on Days 1 and 15 and at Weeks 24 and 26, or twice-daily oral mycophenolate mofetil as a standard-of-care comparator. The primary endpoint — the proportion of patients with a first morning urine protein-creatinine ratio of no more than 0.2 g/g at Week 52 without relapse from Week 8 to Week 52 — was met, with the obinutuzumab group achieving a 95% sustained complete remission at Week 52 versus 73% with mycophenolate mofetil.
Obinutuzumab is a glycoengineered Type II anti-CD20 monoclonal antibody that depletes B cells through enhanced direct cell death and antibody-dependent cellular cytotoxicity, effects conferred by modification of its Fc region that distinguishes it from Type I anti-CD20 antibodies such as rituximab. In INS, sustained B cell depletion is thought to interrupt the immune dysregulation that drives podocyte injury and proteinuria relapse.