Subcutaneous delivery feasible for anifrolumab in SLE
medwireNews: Phase 2 study data suggest that subcutaneous administration is a feasible option for treatment with the type I interferon receptor inhibitor anifrolumab in patients with systemic lupus erythematosus (SLE).
As previously reported by medwireNews, intravenous anifrolumab has already shown clinical efficacy in people with SLE, but the inconvenience of intravenous administration prompted Catharina Lindholm (AstraZeneca, Gothenburg, Sweden) and colleagues to investigate how the drug performs when delivered subcutaneously.
The international study included 36 patients (mean age 45 years, 89% women) with SLE with a high type I interferon 4-gene signature (IFI27, IFI44, IFI44L, and RSAD2) and active skin disease.
The participants were randomly assigned to receive subcutaneous anifrolumab 150 mg (n=14), 300 mg (n=13), or placebo (n=9) every 2 weeks for 50 weeks in addition to standard therapy, and the treatment completion rates were 71%, 77%, and 100%, respectively.
The researchers report in The Lancet Rheumatology that, at week 12, pre-dose mean anifrolumab trough serum concentrations were 19.82 μg/mL among patients who received the 150 mg dose and 60.28 μg/mL among those who received the 300 mg dose, while the ratio between the two doses was more than 2.0 from week 4 to week 52.
Lindholm et al say this shows that the serum drug concentrations were more than dose proportional and the pharmacokinetics were nonlinear.
The investigators also measured the median percentage neutralization of the type I interferon gene signature. At week 12, it was 88.0% with anifrolumab 150 mg, 90.7% with anifrolumab 300 mg and 18.5% with placebo, and these values were sustained until week 52.
In line with this, more patients in the anifrolumab 150 mg and 300 mg groups had type I interferon gene signature neutralization of at least 75% at week 12 than in the placebo group, at 67% and 77% versus 11%, respectively.
Lindholm and team note that the “safety and tolerability of subcutaneous anifrolumab was similar to that of intravenous anifrolumab.” The most commonly reported adverse events were upper respiratory tract infection, nasopharyngitis, bronchitis, and headache.
Serious adverse events occurred in 22% of patients who received anifrolumab (four patients in the 150 mg group and two in the 300 mg group) and in none of those who received placebo. There were no treatment-related deaths.
In exploratory efficacy analyses, the proportion of patients who had an improvement in the Cutaneous Lupus Erythematosus Disease Area and Severity Index was similar across the treatment groups at week 12 but was greater among the anifrolumab-treated patients at weeks 24 and 52.
Lindholm and co-authors conclude: “The pharmacokinetics, pharmacodynamics, and safety data from these studies support the feasibility of subcutaneous administration of anifrolumab.”
They caution however that the “study’s eligibility requirement of a high type I interferon 4gene signature limits the generalisability of our results to patients with a similar gene signature.”
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