Obinutuzumab up for approval as lupus nephritis treatment in US
FDA agrees to review approved blood cancer therapy for lupus complication
The U.S. Food and Drug Administration (FDA) has agreed to review an application by Roche seeking approval of obinutuzumab for the treatment of lupus nephritis, a lupus complication marked by kidney inflammation and damage.
Developed by Roche’s subsidiary Genentech and Biogen, obinutuzumab is an antibody-based treatment, already approved for certain blood cancers, that was found in a clinical trial to ease symptoms of kidney disease in lupus nephritis patients. The therapy is marketed for cancer as Gazyva in the U.S. and Canada, and as Gazyvaro in other regions.
The request, submitted in the form of a supplemental biologics license application, or sBLA, is based on data from the ongoing Phase 3 REGENCY trial (NCT04221477). That trial assessed the efficacy and safety of obinutuzumab against a placebo, when given alongside standard of care, in 271 adults with lupus nephritis.
The FDA’s final decision on obinutuzumab’s approval for lupus nephritis is now expected by October. A similar application is also being prepared for submission to health authorities in Europe.
“In people with lupus nephritis, Gazyva/Gazyvaro demonstrated a complete renal response benefit, a meaningful clinical outcome linked to preservation of kidney function, and slowing or prevention of end-stage kidney disease,” Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, said in a company press release.
Garraway added: “The FDA’s sBLA acceptance for Gazyva/Gazyvaro [recognizes] the need to provide a more effective treatment option for people living with this devastating disease.”
Lupus nephritis treatment approved for cancer in US as Gazyva
Lupus occurs when malfunctioning immune B-cells generate antibodies that mistakenly attack the body’s own tissues and organs. Many adults with lupus eventually develop lupus nephritis, a serious condition characterized by impaired kidney function.
In a large portion of cases, these patients do not respond well to existing lupus treatments and may progress to kidney failure, requiring dialysis or a kidney transplant.
Obinutuzumab works by binding to CD20, a protein found on the surface of B-cells, triggering their destruction. Due to this mode of action, the therapy is believed to help eliminate the overactive B-cells driving the damaging autoimmune response seen in lupus.
Given the relatively young age of onset, people with lupus nephritis experience more years of disease-related complications and decreased quality of life due to the significant burden of this illness. We are hopeful for a new treatment option that can effectively reduce these risks and improve the health of all people affected by this disease.
Results from REGENCY, which backed the new application, showed the trial met its main goal, with significantly more patients achieving a complete renal response after 76 weeks, or about 1.5 years, of treatment with obinutuzumab versus standard of care alone (46.4% vs. 33.1%). To achieve a complete renal response, patients had to meet certain criteria associated with kidney function improvements. At the same time, patients could not require rescue therapy, fail to respond to treatment, withdraw from the study, or die.
At week 76, a significantly larger proportion of patients who had been treated with obinutuzumab in addition to standard care achieved a complete renal response. This occurred alongside a reduction in the use of corticosteroids (42.7% vs. 30.9%) and the attainment of a more favorable reduction in the excess levels of proteins in the urine (55.5% vs. 41.9%), the data showed.
Complement levels and reductions in anti-dsDNA antibodies, two markers of lupus disease activity and inflammation, also showed clinically meaningful improvements. Obinutuzumab’s safety profile in the study was also consistent with what was observed in patients with blood cancers.
Louise Vetter, president and CEO of the Lupus Foundation of America, noted that lupus nephritis is “potentially life-threatening” and “debilitating” for patients.
“Given the relatively young age of onset, people with lupus nephritis experience more years of disease-related complications and decreased quality of life due to the significant burden of this illness. We are hopeful for a new treatment option that can effectively reduce these risks and improve the health of all people affected by this disease,” Vetter said.
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