First New Drug Approved for Idiopathic Nephrotic Syndrome in 70 Years

The FDA expanded the indications for the B-cell depleter obinutuzumab (Gazyva) to include idiopathic nephrotic syndrome, the agency announced on Friday, the first new option for the rare kidney disease in more than half a century.

The CD20-directed cytolytic antibody injection is indicated to reduce the risk of relapse in patients 2 years and older with frequently relapsing or steroid-dependent childhood-onset idiopathic nephrotic syndrome who are in complete remission.

Obinutuzumab targets B cells to control disease activity and can lead to longer lasting remissions, marking the first new treatment in idiopathic nephrotic syndrome in 70 years, according to a press release from drugmaker Genentech.

Data from the phase III INShore study supported the approval. In the 85-participant, open-label trial, a greater proportion of patients achieved complete remission at week 52 with obinutuzumab compared with twice-daily oral mycophenolate mofetil, a commonly used standard-of-care therapy (95% vs 73%).

Key secondary endpoints also showed statistically significant and clinically meaningful benefits with obinutuzumab, including an increase in the proportion of patients with overall relapse-free survival, a longer median time to first relapse or death, and fewer relapses from baseline to week 52.

Idiopathic nephrotic syndrome is a kidney-related autoimmune disease in which large amounts of protein leak into the urine, leading to hypoalbuminemia. The condition can also lead to high cholesterol and other complications, such as infections and blood clots that can block small blood vessels.

“For too long, patients living with idiopathic nephrotic syndrome have had to endure unpredictable relapses, prolonged steroid use, and the constant threat of disease progression,” Andi Callaway, founder and president of the Nephrotic Syndrome Foundation, said in a statement.

The approval “marks a shift that enables patients and families facing this debilitating disease to raise expectations for care and look ahead with optimism for a brighter future,” Callaway added.

No new safety signals with obinutuzumab were observed in INShore, the drugmaker noted.

The most common adverse events were upper respiratory tract infection, infusion-related reactions, ear infection, pneumonia, influenza, neutropenia, bronchitis, COVID, conjunctivitis, and urinary tract infection. The label carries a boxed warning regarding hepatitis B virus reactivation and progressive multifocal leukoencephalopathy.

Prescribing information also warns against infusion-related reactions, hypersensitivity reactions including serum sickness, tumor lysis syndrome, serious or fatal infections, neutropenia, thrombocytopenia, disseminated intravascular coagulation, and embryo-fetal toxicity. Live virus vaccines should also be avoided until B-cell recovery.

This marks the second approval of obinutuzumab for an autoimmune-mediated disease, following its approval in adult lupus nephritis last year. It is also indicated to treat chronic lymphocytic leukemia and follicular lymphoma.

Obinutuzumab is being investigated in pediatric lupus nephritis and is under FDA review for primary membranous nephropathy and for systemic lupus erythematosus, based on the positive phase III MAJESTY and ALLEGORY trials.