On the heels of last week’s lupus nephritis nod from the FDA, Roche’s Gazyva is proving once again that it still has new tricks despite its 12 years on the market—and not just in its original oncology field, either.
Pitted against the immunosuppressant mycophenolate mofetil (MMF), Roche’s CD20-targeting antibody Gazyva (obinutuzumab) helped more kids and young adults with idiopathic nephrotic syndrome (INS) achieve sustained remission after one year, according to a top-line readout from the Swiss drugmaker’s late-stage INShore trial.
Improvements associated with Gazyva in the study—which enrolled 85 people with INS between the ages of 2 and 25 years old—were statistically significant and clinically meaningful, allowing the trial to hit its primary endpoint, Roche’s Genentech unit said in an Oct. 28 press release.
Roche did not disclose detailed results from the study Tuesday, noting that it will share the full readout at a future medical meeting. Emboldened by the trial, Roche said it also plans to provide the data to global regulators, including the FDA and the European Medicines Agency.
Gazyva was originally greenlighted in 2013 to treat chronic lymphocytic leukemia, and, up until last week, the drug’s four approved indications were all in the field of oncology.
Oct. 20, however, Gazyva won FDA approval to treat adults with active lupus nephritis who are taking standard therapy. Like INS, lupus nephritis, which can develop from the most common form of the disease, systemic lupus erythematosus (SLE), is an immune-mediated condition that predominantly affects the kidneys.
Roche figures that Gazyva, by targeting the CD20 protein, could tackle a range of immune-mediated kidney and kidney-related conditions driven by disease-causing B cells.
In the case of INS, the autoimmune disease—typically diagnosed during early childhood—is defined by “unpredictable” relapses that lead to fatigue, swelling, weight gain and greater vulnerability to infections and clotting, Roche explained. The condition may also cause anxiety and depression triggered by “fear of relapse and social isolation,” the company added.
Steroids remain the cornerstone of current INS treatment, according to Roche, but the potential for serious side effects limits long-term use, and many patients still experience relapses under this approach.
In the INShore trial, Roche defined complete INS remission as the absence of relapses during the study period, alongside a low amount of protein in the urine at the 52-week mark.
Gazyva also succeeded across a series of key secondary endpoints, charting improvements over MMF in relapse-free survival, median time to relapse or death, reduction in cumulative corticosteroid dosing from baseline to a year and fewer relapses from baseline to Week 52, Roche said.
On certain other endpoints, however, Gazyva “showed no significant difference” in performance over MMF, Roche admitted. The endpoints where Gazyva showed parity with the immunosuppressant MMF included sustained complete remission, probability of relapse-free survival, the proportion of patients who experienced edema-associated relapse and mean change on a measure of “general fatigue,” among others.
No new safety signals cropped up in the study, and Gazyva’s overall safety profile was on par with results from previous studies of the drug in adults, Roche pointed out.
“These results show that Gazyva may achieve robust disease control with a reduced need for corticosteroids, which are associated with serious side effects over time,” Levi Garraway, M.D., Ph.D., chief medical officer and head of global product development at Roche, said in a statement.
“Idiopathic nephrotic syndrome is a severe and chronic kidney disease usually diagnosed in early childhood, yet meaningful treatment progress has been limited,” he continued. “As a targeted therapy, Gazyva has the potential to help address this unmet need and we look forward to sharing the data with health authorities.”
While the INS market remains generally untapped by novel branded drugs, Gazyva will face greater competition in its new lupus nephritis indication, where GSK’s Benlysta is dominant and AstraZeneca’s Saphnelo first graced the stage in 2021. Aside from lupus nephritis and INS, Roche is also testing Gazyva in membranous nephropathy, rare immune-mediated kidney diseases and SLE.
In 2024, while still operating exclusively in the realm of blood cancers, Roche’s antibody drug secured (PDF) full-year sales of 910 million Swiss francs (roughly $1.15 billion), growing 16% over 2023.