Genentech targets lupus market for Gazyva with positive Phase III results

Genentech, a subsidiary of Roche, has presented encouraging Phase III trial results to the US Food and Drug Administration (FDA) for its CD20-targeting drug, Gazyva (obinutuzumab), as it seeks to enter the lucrative lupus market. The current treatment landscape for systemic lupus erythematosus (SLE) and lupus nephritis, primarily served by generic medications, has seen limited approval of targeted biologics over the last half-century. Notably, only a few such as GSK's Benlysta (belimumab) and AstraZeneca's Saphnelo (anifrolumab) have been approved specifically for SLE.

The significance of the Phase III data for Gazyva lies in its potential to become the first CD20-directed therapy for lupus nephritis with regulatory endorsement, should it gain approval. The REGENCY trial (NCT04221477) involved 271 patients and demonstrated that 46.4% of those receiving Gazyva in combination with standard treatment achieved a complete renal response after 76 weeks. This contrasts with a 33.1% response rate in the placebo group. These results were disclosed at the World Congress of Nephrology in New Delhi, India, with confirmations that the data has been submitted to both the FDA and the European Medicines Agency (EMA) for review.

Lupus nephritis is a serious form of SLE characterized by kidney inflammation, which substantially heightens the risk of organ damage and mortality. Current management strategies largely depend on immunosuppressive agents like steroids and mycophenolate mofetil (MMF), which carry significant safety concerns, including increased infection risk and potential for organ toxicity over time.

The promising outcomes from the REGENCY trial emerge over a decade after the unsuccessful application of another Roche B-cell depleting agent, Rituxan (rituximab), for lupus nephritis. Although developed in partnership with Biogen and widely utilized off-label for the condition, Rituxan was not approved by the FDA following the Phase III LUNAR trial (NCT00282347) in 2012, which did not demonstrate a meaningful renal outcome improvement. Notwithstanding, real-world experiences have continued to support Rituxan's use in stubborn lupus cases, reportedly generating about $2.5 billion in sales in 2023, despite its off-label status.

Gazyva, like Rituxan, is a monoclonal antibody targeting the CD20 protein on B cells, but it is glycoengineered to enhance B-cell depletion. Already approved in the United States for various hematological cancers, including chronic lymphocytic leukemia and follicular lymphoma, Gazyva's potential approval for lupus nephritis could significantly widen its market footprint. According to GlobalData, the drug could achieve sales of up to $1.7 billion by 2030 if approved for this new indication.

Beyond lupus nephritis, Genentech is also researching Gazyva's applicability in other autoimmune disorders such as SLE, childhood-onset idiopathic nephrotic syndrome, membranous nephropathy, and pediatric lupus nephritis. Although Genentech has not specified a timeline for regulatory decisions, the company intends to collaborate closely with relevant agencies to expedite Gazyva's approval for lupus nephritis. The global market for SLE and lupus nephritis is projected to climb to $4.8 billion by 2031, underscoring the significant commercial potential for effective new treatments in this domain.