BIIB059 safe, efficacious in systemic lupus erythematosus
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BIIB059 significantly reduces total active joint counts among patients with systemic lupus erythematosus, with a rate of serious adverse events and infection similar to placebo, according to a speaker at ACR Convergence 2020.
“There are three types of interferons — types 1, 2 and 3 — and type 1 interferons, consisting of five subtypes, play a key role in lupus pathogenesis,” Richard Furie, MD, chief of the division of rheumatology at Northwell Health, in New York, told attendees at the virtual meeting. “There are several lines of evidence to support this association, including elevated levels of interferon- in lupus patients, interferon gene signatures in the majority of patients, and recent clinical trial results demonstrating clinical effectiveness of anifrolumab, a monoclonal antibody that inhibits the interferon pathway by blocking the type 1 interferon receptor.”
“Plasmacytoid dendritic cells, responsible for the bulk of type 1 interferon production in lupus, are abundant in the skin of lupus patients,” he added. “A protein unique to plasmacytoid dendritic cells is known as blood dendritic cell antigen, or BDCA2 for short. When ligated by an antibody to BDCA2, known as BIIB059, BDCA2 is internalized, and type 1 interferon, cytokine and chemokine production is inhibited. In a phase 1 study of 12 lupus patients with cutaneous disease who were treated with a single dose of BIIB059 or placebo, we demonstrated inhibition of the interferon gene signature in peripheral blood, downregulation of cutaneous expression in interferon-regulated protein, and clinical improvement in skin activity as measured by CLASI.”
To examine the safety and efficacy of BIIB059 (Biogen) among patients with SLE as well as cutaneous lupus erythematosus, Furie and colleagues conducted the two-part phase-2 LILAC trial. Furie presented the results of part A of the trial, which focused specifically on SLE. For that part, the researchers enrolled 120 adults who fulfilled four of the 11 revised 1997 ACR classification criteria, with at least four tender and swollen joints, based on 28-joint assessment, as well as active skin disease based on SLEDAI-2K, and positive ANA or elevated anti-dsDNA antibodies.
Participants were randomized into one of two groups, with 64 treated with 450 mg of BIIB059, and 56 receiving placebo, administered subcutaneously every 4 weeks for 20 weeks, as well as an additional dose at week 2. Concomitant SLE therapy had to have been initiated at least 12 weeks — and remain stable for at least 4 weeks — prior to randomization and throughout the study. Meanwhile, oral corticosteroids were limited to 20 mg of prednisone per day— or equivalent — with mandatory tapering started 4 weeks after the initial dose of study therapy.
The primary endpoint was the change in total active joint count — defined as the sum of tender and swollen joints — from baseline to week 24. Secondary endpoints compared the proportions of participants with 50% improvement from baseline in CLASI-A score and the proportions of participants who achieved an SRI-4 response at week 24. The researchers also examined safety.
In all, 90.6% and 89.3% of participants in the BIIB059 and placebo groups completed the study, respectively.
According to the researchers, there was a significant difference in least squares mean absolute changes from baseline in the total active joint count between the placebo group, with a change of –11.6 and the BIIB059 arm, with a change of –15.0 (P = .037). In addition, there was a 26-percentage point difference (95% CI, 9.46-43.24) in the SRI-4 response rate between the BIIB059 and placebo groups at week 24.
Although the BIIB059 group demonstrated a higher CLASI-50 response rate than those who received a placebo, this finding was not statistically significant.
Regarding safety, 67.9% and 59.2% of participants in the placebo and pooled BIIB059 groups, respectively, experienced any adverse event.
“Receipt of BIIB059 through week 20 was associated with a significant reduction in the total active joint count, a significant improvement in the SRI response rate, and a higher percentage of those who achieved a CLASI-50 response,” Furie said. “Serious adverse event and infection rates were similar to the placebo group.”
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Furie R. Abstract 0935. Presented at: ACR Convergence 2020; November 5-9, 2020 (virtual meeting).
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