FDA Approves Gazyva for Lupus Nephritis in Adults

The FDA has approved Genentech’s Gazyva (obinutuzumab) for the treatment of lupus nephritis in adults, according to a news release published today. Gazyva is the first and only anti-CD20 monoclonal antibody approved for lupus nephritis and should be used in combination with the standard of care.

Lupus is an autoimmune disease that affects millions of people worldwide. In lupus, the immune system produces autoantibodies, which mistakenly attack healthy tissue in the kidneys, brain, lungs, skin, blood and joints. Approximately 90% of lupus patients are women, diagnosed between the ages of 15 and 45. There is an even higher prevalence in Black, Latinx, Indigenous, Asian and Pacific Islander people.

Lupus nephritis is a kidney-specific complication of lupus that causes severe inflammation that most commonly manifests within the first five years of lupus diagnosis. Symptoms include weight gain, swelling, an increase in urination (especially at night), bloody and foamy urine and high blood pressure. Approximately 50% of lupus patients develop lupus nephritis, and up to 30% of patients with lupus nephritis develop end-stage kidney disease, which results in transplantation or dialysis.

This approval was made using the results from the phase 2 NOBILITY and phase 3 REGENCY clinical trials, which tested the effectiveness of Gazyva in 200 patients being treated with standard lupus therapy consisting of mycophenolate mofetil and corticosteroids or mycophenolate mofetil/mycophenolic acid and corticosteroids.

The most common adverse reactions reported were upper respiratory tract infection, COVID-19 and urinary tract infections, occurring in at least 5% of patients.

The most common serious adverse reactions were COVID-19 (5.5%), pneumonia (4.5%) and neutropenia (3.5%).

Gazyva is an anti-CD20 monoclonal antibody that works by attaching to CD20, a protein found on certain types of B cells that drive inflammation in lupus.

“Obinutuzumab, the first anti-CD20 therapy currently approved for lupus nephritis, enhances B-cell depletion compared to previously studied anti-CD20 antibodies, providing complete renal response in nearly half of patients studied, without increasing the frequency of serious safety events,” Richard Furie, M.D., chief of the division of rheumatology at Northwell in New York State and the study’s lead investigator and member of Lupus Clinical Investigators Network, said in the news release. “B cells play a critical role in lupus nephritis pathogenesis and currently are a popular target not only for lupus but also for other types of inflammatory diseases.”

Gazyva comes in a 1,000-mg single dose vial, according to the prescribing information. The recommended dosage is 1,000 mg during the initial infusion, week 2, and weeks 24 and 26, and then every 6 months thereafter. During the initial infusion, the dose can be increased by 50-mg every hour for a maximum of 400-mg per hour. During all other infusions, dosage can be increased by 100-mg an hour every 30 minutes for a maximum of 400-mg per hour.

Patients with no signs of grade 3 or higher adverse reactions during initial infusion may receive an accelerated 90-minute infusion for dose two and thereafter.

The patient may be pretreated with an intravenous glucocorticoid, administered at least one hour before Gazyva, or acetaminophen or an antihistamine at least 30 minutes before Gazyva infusion.

Gazyva was originally approved by the FDA in 2013 for the treatment of chronic lymphocytic leukemia when used in combination with the chemotherapy drug chlorambucil.