Atrasentan and Obinutuzumab Show Promise for Rare Kidney Diseases in Phase 3 Trials

Final results from a phase 3 study evaluating atrasentan in adults with immunoglobulin A (IgA) nephropathy showed the drug slowed kidney function decline, while a separate phase 3 trial of obinutuzumab demonstrated significantly higher remission rates in primary membranous nephropathy (pMN) patients compared to standard immunosuppressant therapy.

Atrasentan is an endothelin receptor agonist currently marketed under the brand name Vanrafia to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid disease progression. The drug received approval through the Food and Drug Administration's accelerated approval pathway in April 2025 based on interim results from the ALIGN trial (ClinicalTrials.gov Identifier: NCT04573478). The study met its primary endpoint demonstrating a reduction in proteinuria with atrasentan vs placebo in IgA nephropathy patients at week 36.

The key secondary endpoint for the final analysis was the change from baseline to week 136 in kidney function as measured by estimated glomerular filtration rate (eGFR). Findings showed treatment with atrasentan showed a difference of 2.59 mL/min/1.73m2 (P =.039) in eGFR change from baseline compared with placebo at week 132 (end of treatment period), as well as a difference of 2.39 mL/min/1.73m2 vs placebo (P =.057) at week 136 (4 weeks after end of treatment).

Clinically meaningful effects were also seen in prespecified exploratory groups of patients receiving sodium-glucose co-transporter-2 inhibitors. The safety profile of the drug was consistent with that observed in previous analyses. The most common adverse reactions reported with atrasentan in clinical trials were peripheral edema and anemia. The Company intends to seek traditional approval for Vanrafia in 2026 based on the final data from the ALIGN study.

The phase 3 MAJESTY trial of anti-CD20 antibody Gazyva (obinutuzumab), known as Gazyvaro in some markets, met its primary endpoint, with significantly more patients achieving disease remission with the drug compared to immunosuppressant tacrolimus, the active control. In pMN, the immune system launches an attack on the glomeruli structures of the kidney responsible for its blood filtering function, leading to a gradual and progressive decline in renal function. It accounts for 70% to 80% of all membranous nephropathy cases and affects around 88,000 people in the EU and 96,000 in the US.

Up to 30% of people with the disease progress to kidney failure over 10 years, despite current treatment approaches based on immune-suppressing drugs that can also cause significant side effects, such as infections, bone marrow suppression, and cancer. Significantly more people achieved complete remission at two years with Gazyva versus tacrolimus, with a safety profile that was in line with what has previously been reported with the anti-CD20 antibody, which achieved a 25% hike in sales to $1.28 billion last year.

The results also showed a significant improvement with Gazyva on secondary endpoints, such as complete or partial remission at week 104 and complete remission at week 76. The results will be presented at an upcoming medical meeting and submitted to regulators in the US, Europe, and other parts of the world.

Originally developed as a more-potent follow-up to a long-established CD20-directed antibody for blood cancers and launched in 2013, Gazyva is seeing a spike in use thanks to its recent approval for lupus nephritis, a kidney complication of autoimmune disease systemic lupus erythematosus (SLE). The drug has also reported positive phase 3 results in idiopathic nephrotic syndrome and in reducing disease activity more broadly in SLE.