Roche trial offers hope to patients with rare kidney disease

A study of Roche's Gazyva has raised the prospect of a first approved therapy for primary membranous nephropathy (pMN), a rare autoimmune kidney disorder.

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.

According to top-line results announced by Roche this morning, 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 – which will be presented at an upcoming medical meeting and submitted to regulators in the US, Europe, and other parts of the world – 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.

"These results demonstrate that Gazyva/Gazyvaro may help more people with primary membranous nephropathy achieve complete remission, maintain kidney function for longer and delay or potentially prevent the onset of life-threatening complications," said Levi Garraway, Roche's chief medical officer.

Originally developed as a more-potent follow-up to Roche's long-established CD20-directed antibody Rituxan (rituximab) 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).

Roche has aspirations to add to the drug's indications in kidney diseases even further, and has also reported positive phase 3 results with the drug in idiopathic nephrotic syndrome and in reducing disease activity more broadly in SLE. GlobalData has predicted that sales of the drug could reach $1.8 billion or more in 2030, fuelled by expanded indications.