FDA approval of Gazyva offers new option for pediatric INS

The US Food and Drug Administration (FDA) has approved Gazyva (obinutuzumab; 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 idiopathic nephrotic syndrome (INS) who are in complete remission. Announced September 25, 2026, the approval marks the first FDA-approved treatment option for INS in 70 years, offering a new approach to managing a disease characterized by recurrent relapses and prolonged reliance on corticosteroids. For pediatric patients and their families, the approval represents an opportunity to reduce disease burden and potentially limit the complications associated with repeated steroid exposure.

The approval was supported by results from the phase 3 INShore trial, which demonstrated that 95% of patients treated with Gazyva experienced no relapses after week 8 and remained in complete remission at week 52, compared with 73% of patients receiving mycophenolate mofetil (MMF). Gazyva, a B-cell–depleting monoclonal antibody, also demonstrated statistically significant improvements in relapse-free survival, time to first relapse or death, and the number of relapses through week 52 compared with MMF. No new safety signals were identified, although clinicians must consider risks associated with B-cell depletion, including serious infections, infusion-related reactions, and implications for vaccination timing.

To better understand the clinical significance of this approval and its potential impact on pediatric nephrology practice, Contemporary Pediatrics spoke with Keisha L. Gibson, MD, MPH, a pediatric nephrologist at the University of North Carolina School of Medicine. In the following Q&A, Gibson discusses how Gazyva could change the management of frequently relapsing and steroid-dependent INS, considerations for identifying appropriate pediatric patients, and what clinicians should know about balancing the potential benefits of sustained remission with treatment-related risks and long-term monitoring.

Contemporary Pediatrics: For pediatricians who manage or refer children with idiopathic nephrotic syndrome, what is most important to understand about this FDA approval of obinutuzumab for patients aged 2 years and older?

Keisha L. Gibson, MD, MPH: Most pediatricians are likely not managing INS, but there are certainly a few who do because of a lack of pediatric nephrologists in their state/geographic area. It is important to know that obinutuzumab is and should be used as steroid-sparing therapy only in patients who have clinically declared themselves as frequent relapsers or steroid-dependent.

Contemporary Pediatrics: Which children with frequently relapsing or steroid-dependent nephrotic syndrome may be appropriate candidates for obinutuzumab, and where might it fit into the current treatment pathway?

Gibson: Obinutuzumab may be considered for any child with frequently relapsing or steroid-dependent nephrotic syndrome. It may also be considered for any child with INS that has displayed overt side effects from steroids. The decision between whether to choose obinutuzumab or other steroid-sparing therapies like mycophenolate mofetil or a calcineurin inhibitor should really be shared decision-making between the family and their provider. Obinutuzumab is the only option for steroid-sparing therapies that is FDA- and EMA-approved, but there may be reasons why a family may prefer another option (for example, if there's a history of severe needle phobia or if access is limited by cost or availability).

Contemporary Pediatrics: In the INShore trial, 95% of patients treated with obinutuzumab had no relapses after week 8 and were in complete remission at 1 year, compared with 73% receiving mycophenolate mofetil. How should clinicians interpret those findings in practice?

Gibson: Clinicians can look at these results and feel assured that both options are very reasonable options for steroid-sparing therapy in these patients. Although the positive results of this primary analysis of the Inshore trial are compelling, we really should avoid thinking that this is enough to displace MMF as a very reasonable option for management in this often complicated-to-manage group of patients. Our current 2025 KDIGO guidelines still list rituximab, MMF, calcineurin inhibitors, cyclophosphamide, and levamisole as all reasonable steroid-sparing options in an unbiased order. Obinutuzumab has yet to be incorporated, of course, in these guidelines, but I would venture to say that we'll see it soon. I think there's going to be a real role for this drug in patients with more difficult-to-control disease where a durable B cell depletion can offer a clear advantage. MMF has a well-established low toxicity profile and good efficacy as long as therapeutic levels are achieved. We need to remember that obinutuzumab, like other anti-CD20 depleting antibodies, carries a risk for infusion-related reactions and other more long-term complications like neutropenia, low antibody levels (hypogammaglobulinemia), which may at times require IVIG. Again, the shared decision-making between families and their providers will be critical.

Contemporary Pediatrics: Because prolonged or repeated corticosteroid exposure can be a major concern in children, how could this treatment affect steroid use and the longer-term management of these patients?

Gibson: It would be challenging to argue against the fact that, of all the treatments for patients with frequently relapsing or steroid-dependent INS, chronic steroid exposure carries the longest list of unpalatable side effects and toxicity. Access to these steroid-sparing therapies is critical in avoiding that toxicity. Therapies like obinutuzumab provide families with the potential option of a treatment that does not require daily or alternate-day dosing for an extended period of time.

Contemporary Pediatrics: What safety considerations, monitoring requirements, or counseling points should pediatricians be aware of when a child is receiving obinutuzumab, particularly given its B-cell–depleting mechanism of action?

Gibson: Infusion reactions in several study series of children who received obinutuzumab were not uncommon. This is something that families should be aware of and providers completing these infusions should be prepared to respond to. As is true for almost all steroid-sparing therapies in children with nephrotic syndrome, a higher risk for infection should be respected. Prior to treatment with obinutuzumab, vaccination status should be confirmed, and any live vaccines not previously administered should be avoided during depletion. HBV serology in particular should be confirmed prior to treatment. Following treatment, serial CBCs to monitor for lymphopenia and IgG levels to monitor for hypogammaglobulinemia should be routinely performed.

Reference

Genentech. FDA approves Gazyva for idiopathic nephrotic syndrome in patients aged 2 and older. News release. Published September 25, 2026. Accessed October 15, 2026. https://www.gene.com/media/statements/ps_092526