NOBILITY: Gazyva sustains safety, efficacy against lupus nephritis over 2 years
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Obinutuzumab provides sustained clinical benefit through 2 years among patients with lupus nephritis, with treatment efficacy maintained 18 months after the final infusion, according to data presented at ACR 2020.
Results of the phase 2 NOBILITY trial also showed that obinutuzumab (Gazyva, Genentech) was well-tolerated with “no unexpected safety findings” by week 104.
“Decades ago, it was felt that B cell depletion would be a terrific treatment strategy for SLE,” Richard Furie, MD, of Northwell Health, in Great Neck, New York, told Healio Rheumatology. “After all, SLE is the prototypic B cell disease as evidenced by the presence of B cell hyperactivity and the production of autoantibodies. Our foray into B-cell depletion in SLE clinical trials unfortunately was not successful. Additional data suggested that a reason for inadequate responses was that B-cell depletion was not profound enough.”
He added, “With obinutuzumab showing superior B-cell depletion in vitro as well as in head‐to‐head clinical trials in B cell malignancies, it was decided to try once again in a lupus nephritis clinical trial.”
To determine whether enhanced B-cell depletion with obinutuzumab could improve responses in lupus nephritis, Furie and colleagues randomized patients with class 3/4 lupus nephritis (n=125) to receive either blinded obinutuzumab or placebo infusions at weeks 0, 2, 24 and 26. The primary endpoint was complete renal response at week 52, with secondary endpoints including overall renal response and modified complete renal response.
According to study results, 102 patients (82%) completed 104 weeks of follow up. Complete renal response was demonstrated to be greater with obinutuzumab than placebo at week 52 (35% vs. 23%, P = .115), week 76 (40% vs. 18%, P = .007) and week 104 (41% vs. 23%, P = .026). Additionally, at week 104, patients treated with obinutuzumab exhibited greater improvement in eGFR, UPCR, anti-dsDNA, C3 and C4, and fewer of these patients required initiation of a new rescue therapy through week 104.
“The NOBILITY study met its primary endpoint at week 104, which adds sustained long‐term efficacy to the positive 76‐ and 52‐ week data presented last year,” Furie said. “Gazyva, in combination with standard of care, demonstrated superiority compared to placebo plus standard of care alone.”
“What is so striking about the results at week 104 is that the treatment was last given 18 months prior to this endpoint, emphasizing the longevity of effect,” he added. “A durable response to a therapeutic intervention is so crucial in SLE management.”
The researchers detected peripheral B-cells in 92% of patients treated with obinutuzumab at week 104. Notably, serious adverse events were more common in the placebo group than in the obinutuzumab group (30% vs. 25%), as were serious infections (18% vs. 8%) and deaths (4 vs. 1).
“Our current state‐of‐the‐art therapies for lupus nephritis are inadequate with about one‐third of
patients achieving a complete response,” Furie said. “Since those who do better initially do better long‐term, our patients need more effective therapies for this severe complication. The phase 3 REGENCY study of obinutuzumab in lupus nephritis is now enrolling, and we expect to reproduce the excellent results seen in the phase 2 NOBILITY trial.”
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Furie R. Abstract #988. Presented at: ACR Convergence 2020; November 5-9, 2020 (virtual meeting).
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