Roche submits Gazyva lupus results to FDA

Nearly 16 years after the underwhelming outcomes of Rituxan in treating lupus, Roche's Genentech has achieved promising results with another B cell-targeting drug, Gazyva, specifically for lupus nephritis. The company is now advancing plans to seek FDA approval for this treatment.

On Friday, Genentech revealed that Gazyva successfully met the primary endpoint in a crucial clinical trial. The drug, when added to standard care for lupus nephritis, improved the percentage of patients achieving complete renal response by 13% compared to those who did not receive it. During the Phase 3 trial, 271 participants were administered either Gazyva (known scientifically as obinutuzumab) or a placebo alongside standard therapies, which typically involve an immunosuppressive agent and a steroid. After approximately 76 weeks, or a year and a half, 46.4% of the patients treated with Gazyva reached complete renal response, compared to 33.1% in the placebo group.

These findings were unveiled at the annual World Congress of Nephrology held in New Delhi and published in the New England Journal of Medicine. Genentech had already announced in September that the trial had met its primary endpoint, and the recent presentation confirms their intention to share these results with both the FDA and the European Medicines Agency (EMA).

Lupus nephritis is a severe manifestation of lupus, characterized by the immune system attacking the kidneys. In this clinical study, the primary measure of success was complete renal response, which involves evaluating kidney function through two laboratory tests. Achieving this response is seen as a potential indicator of long-term kidney health preservation.

Both Rituxan (rituximab) and Gazyva operate by targeting the CD20 protein present on B cells. Rituximab, a collaboration between Biogen and Genentech, is still occasionally used off-label for treating lupus nephritis, despite the availability of biosimilar alternatives. Researchers believe that Gazyva, which has already been approved for certain blood cancers, achieves a more significant depletion of B cells in lupus patients than rituximab, accounting for its success in this pivotal study where rituximab did not perform as well.

Jay Garg, who leads nephrology and rheumatology globally for Roche and Genentech, remarked, "This is the first and only anti-CD20 treatment to demonstrate benefit in a Phase 3 study for lupus nephritis." He emphasized that while the medical community has had faith in anti-CD20 therapies, this belief was primarily based on single-arm open-label studies that had inherent biases. This study, he noted, serves to validate the community's confidence in anti-CD20 treatments.

The achievement with Gazyva comes at a time when pharmaceutical companies are increasingly exploring the application of immunotherapy techniques, initially developed for cancer, in treating autoimmune diseases. Garg acknowledged the progress made in the field, stating, "We've come a long way." However, he also pointed out that challenges remain, as more than half of the patients in the study did not attain complete renal response.

He expressed optimism about future research, specifically CAR-T cell therapies, which may enhance B cell depletion and lead to more substantial outcomes for patients. The early data from CAR-T therapies in autoimmune conditions have generated excitement, prompting a competitive pursuit among biotechnology and pharmaceutical firms to develop these treatments for autoimmune diseases such as lupus.