Anifrolumab, obinutuzumab show ‘promising results’ for lupus drug pipeline
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Several emerging therapies for lupus have shown promising results in the past year, with anifrolumab and obinutuzumab potentially attracting FDA attention, according to a speaker at the Basic and Clinical Immunology for the Busy Clinician symposium.
“What about our old friend anifrolumab? Anifrolumab was developed as an antibody that is to the receptor for type 1 interferons,” Gregg J. Silverman, MD, of the New York University School of Medicine, told attendees at the virtual meeting. “There was an issue originally when they made antibodies through the type 1 interferons themselves — they were not as effective.”
“The problem is, there are 10 or more different distinct molecules that are type 1 interferons, but one receptor,” he added. “So, trying to have an inhibitor of the receptor itself was looked at in two studies, TULIP-1 and TULIP-2. And now, with these phase 3 studies, they have just put the data together.”
That data was presented at the ACR 2020 Convergence meeting by Victoria Werth, MD, of the University of Pennsylvania. The two, 52-week, randomized, double-blind, placebo-controlled trials had evaluated the efficacy and safety of anifrolumab (AstraZeneca) — administered intravenously in doses of 300 mg every 4 weeks for 48 weeks — in patients with moderately to severely active SLE despite standard-of-care treatment. A total of 360 participants were treated with anifrolumab while 366 received a placebo.
At ACR, Werth reported that anifrolumab was associated with rapid and durable improvements in skin-specific SLE disease activity — based on by Cutaneous Lupus Erythematosus Disease Area and Severity Index- activity scores — among patients with mild to severe baseline cutaneous disease activity.
“You can see that statistically significant benefits were shown from 8 weeks,” Silverman said. “There were some really great benefits, and it was persistent out to 52 weeks. This is something that we may see, and I think the FDA is considering whether this merits approval.”
Obinutuzumab (Gazyva, Genentech), which the FDA granted a “breakthrough therapy” designation for lupus nephritis in September 2019, also had some promising results reported out of ACR 2020, according to Silverman.
That data, which was presented at the time by Richard Furie, MD, of Northwell Health, in New York, had been the product of 2 years of research from the NOBILITY trial, which included 125 patients with class III or IV lupus nephritis. Patients received mycophenolate and steroids and randomized to blinded infusions of either obinutuzumab or placebo on weeks 0, 2, 24 and 26. All patients were followed through week 104.
According to the NOBILITY researchers, the data demonstrated a sustained benefit for obinutuzumab through week 104, approximately 18 months after the final infusion, with no unexpected safety findings. In addition, obinutuzumab was associated with a return of peripheral B-cells by week 104.
“Obinutuzumab has been previously shown to be safe and effective for non-Hodgkin’s lymphoma, and it’s FDA approved, but the question is: ‘What about lupus nephritis?’” Silverman said. “We still need something very potent.”
“We can see in this 2-year study follow-up that 41% of obinutuzumab patients were able to get a complete renal response, compared to 23% with placebo, and the results for a partial response were about 54%,” he added. “When you bring it all together, it really is very statistically significant. Also notable is that the FDA has given it breakthrough special status for accelerated approval.”
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Silverman G. SLE: New perspectives on pathogenesis and emerging novel therapies. Presented at Basic and Clinical Immunology for the Busy Clinician; Feb. 5-6, 2021. (virtual meeting).
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