'I am optimistic': Lupus pipeline features promising B-cell depletion therapies
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SAN DIEGO — Obinutuzumab and ianalumab are two promising B-cell depleting therapies on the horizon for lupus, according to data presented at the 2024 Congress of Clinical Rheumatology West.
“I am optimistic about the future,” Richard A. Furie, MD, chief of the rheumatology division at Northwell Health, in New York, told attendees. “I think it’s just a matter of time before we have more drugs approved, and this means greater outcomes for our patients with lupus.”
Obinutuzumab (Gazyva, Genentech) is an anti-CD20 antibody, similar to rituximab (Rituxan, Genentech), but stronger and more potent, Furie said.
“It has been glycoengineered to get greater antibody-dependent cytotoxicity by about 100-fold,” he added. “It also induces greater direct B cell death.”
Furie was the first author on a phase 2 trial, called NOBILITY, that tested obinutuzumab in lupus nephritis and found “very profound B-cell depletion,” as well as greater complete renal response compared with placebo, he said.
“At 1 year, there’s an effect size of about 12 percentage points,” Furie said. “It grew to about 20 percentage points at 1-and-a-half years and was sustained at 2 years to close to 20%.”
Patients were re-treated at 6 months and demonstrated “a very durable response” up to a 1.5 years after the last dose, according to Furie.
“We just heard 2 days ago that the phase 3 study for obinutuzumab in lupus nephritis, called REGENCY, had a positive outcome, so stay tuned to hear more about those results,” he said.
Furie also highlighted ianalumab (Novartis), which has a dual mechanism of action, depleting B cells as well as blocking the B-cell activating factor (BAFF) pathway, also known as the B lymphocyte stimulator (BLyS) pathway.
The drug first showed “profound B-cell depletion” in a Sjögren’s trial. Additionnally, in a small phase 2 study in systemic lupus erythematosus, ianalumab resulted in significant B-cell depletion and a “very profound” effect size on SLE Responder Index 4 response, according to Furie.
Ianalumab is now undergoing further study in an SLE trial and a lupus nephritis trial, he said.
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Furie RA. Novel Treatments for Systemic Lupus Erythematosus and Lupus Nephritis. Presented at The Congress of Clinical Rheumatology West; Sept. 26-29, 2024. (hybrid meeting).
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