Roche’s Gazyva shows superior efficacy in lupus nephritis treatment, Phase III trial data reveals

Roche has announced promising new data from its phase III REGENCY clinical trial, published in the New England Journal of Medicine, highlighting the superior efficacy of Gazyva/Gazyvaro (obinutuzumab) in the treatment of active lupus nephritis. The trial results underscore Gazyva’s potential to significantly improve kidney outcomes in patients with this life-threatening autoimmune condition, outperforming standard therapies.

How does Gazyva improve lupus nephritis treatment outcomes?

The REGENCY trial demonstrated that nearly half of the participants receiving Gazyva plus standard therapy achieved a complete renal response (CRR)—a critical measure indicating healthy kidney function—compared to those on standard treatment alone. Specifically, 46.4% of patients treated with Gazyva combined with standard therapy (mycophenolate mofetil and glucocorticoids) achieved CRR at 76 weeks, significantly higher than the 33.1% seen in patients treated with standard therapy alone. This difference, marked by an adjusted improvement of 13.4% (95% CI, 2.0%-24.8%; P=0.0232), is both statistically significant and clinically meaningful.

Achieving CRR is vital in managing lupus nephritis because it is directly linked to preserving kidney function and delaying the progression to end-stage kidney disease (ESKD), where dialysis or transplantation becomes necessary. The REGENCY trial results suggest that Gazyva could play a pivotal role in enhancing long-term kidney health for patients struggling with lupus nephritis. Moreover, the improvements observed in complement levels and reductions in anti-dsDNA markers indicate that Gazyva effectively reduces disease activity and inflammation, both of which are critical factors in controlling lupus nephritis progression.

What makes Gazyva different from standard lupus nephritis therapies?

Gazyva is the only anti-CD20 monoclonal antibody to demonstrate a CRR benefit in a phase III randomised trial for lupus nephritis. Its mechanism of action is distinct from traditional therapies. As a Type II engineered humanised monoclonal antibody, Gazyva specifically targets CD20, a protein found on B cells, which are key drivers of inflammation in lupus nephritis. By depleting these disease-causing B cells, Gazyva reduces kidney inflammation and limits further damage, addressing the underlying cause of the disease rather than merely managing its symptoms.

This mechanism contrasts with standard lupus nephritis treatments like corticosteroids and immunosuppressants, which often come with significant side effects and do not directly target the root cause of kidney damage. Additionally, Gazyva’s ability to enable patients to reduce corticosteroid use without compromising treatment efficacy is a noteworthy advancement, as long-term steroid use can lead to complications such as osteoporosis, weight gain, cardiovascular issues, and increased susceptibility to infections. The drug’s targeted approach offers a promising alternative for patients who require more precise, effective treatment options with fewer long-term risks.

What were the key findings of the REGENCY trial?

The REGENCY trial, a double-blind, placebo-controlled, multicentre study, enrolled 271 patients diagnosed with active lupus nephritis. Participants were randomly assigned to receive either biannual intravenous doses of Gazyva plus standard therapy or a placebo with standard therapy. The primary endpoint focused on the proportion of patients achieving CRR at 76 weeks, a timeframe designed to capture meaningful long-term treatment outcomes.

Results from the trial revealed that patients receiving Gazyva were significantly more likely to achieve CRR compared to those on standard therapy alone. Additionally, Gazyva-treated patients demonstrated successful corticosteroid tapering, with 42.7% of them maintaining CRR while reducing their prednisone dosage to 7.5 mg/day or less between weeks 64 and 76, compared to 30.9% in the placebo group (P=0.0421). The reduction in corticosteroid dependency is crucial, as high-dose steroids can lead to adverse effects over time.

Proteinuric response, which reflects a reduction in the amount of protein excreted in the urine and serves as an indicator of improved kidney function, was achieved by 55.5% of patients treated with Gazyva, compared to 41.9% in the standard therapy group (P=0.0227). Furthermore, the incidence of renal-related events and mortality was significantly lower in the Gazyva group (18.9%) compared to the placebo group (35.6%) with a P-value of 0.0026, suggesting that Gazyva not only improves kidney function but also offers protection against disease progression and life-threatening complications.

How does Gazyva’s safety profile compare to existing treatments?

Gazyva’s safety profile in the REGENCY trial was consistent with its well-documented performance in treating haematological cancers, for which it is already approved in over 100 countries. The safety data showed that Gazyva was well-tolerated, with adverse events comparable to those observed in the standard therapy group. No new safety concerns emerged during the trial, reinforcing the drug’s potential as a safe and effective option for lupus nephritis patients.

Dr. Richard Furie, Chief of Rheumatology at Northwell Health, highlighted that the ability of Gazyva to deliver strong clinical outcomes without increasing adverse effects is particularly encouraging. He noted that patients receiving obinutuzumab not only achieved better kidney responses but also managed to taper corticosteroid doses, which is a major win given the risks associated with long-term steroid use. This balance between efficacy and safety is critical for chronic conditions like lupus nephritis, where patients often require lifelong management.

What are the broader implications for lupus nephritis treatment?

Lupus nephritis affects approximately 1.7 million people globally, predominantly women of colour in their childbearing years. Despite available treatments, up to one-third of lupus nephritis patients progress to end-stage kidney disease within 10 years, facing the prospect of dialysis or kidney transplantation. The disease disproportionately affects younger women, particularly women of colour, highlighting significant disparities in healthcare outcomes and access to effective treatments.

The REGENCY trial’s results are especially impactful because they offer hope for a more effective treatment strategy that could change the trajectory of the disease. Dr. Levi Garraway, Roche’s Chief Medical Officer, emphasised the urgency of this breakthrough, stating that Gazyva addresses an unmet medical need by providing superior disease control compared to standard therapies. The drug’s ability to improve kidney outcomes while reducing corticosteroid use could significantly enhance the quality of life for lupus nephritis patients, reducing both disease-related complications and treatment-related side effects.

What’s next for Gazyva in lupus nephritis research?

Following the positive REGENCY trial results, Roche has shared data with regulatory authorities, including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), potentially paving the way for expanded indications of Gazyva in lupus nephritis. Regulatory approval would mark a significant milestone, offering a new, more effective treatment option for patients worldwide.

Gazyva is also being investigated in other kidney-related conditions, including membranous nephropathy, childhood-onset idiopathic nephrotic syndrome, and systemic lupus erythematosus. These ongoing studies aim to broaden the therapeutic applications of Gazyva and provide further insights into its long-term impact on kidney health and overall patient outcomes. With its demonstrated ability to improve complete renal response rates, reduce steroid dependency, and slow disease progression, Gazyva is poised to redefine the standard of care for lupus nephritis and related conditions.