The FDA approves anifrolumab-fnia injection (Saphnelo; AstraZeneca) for the treatment of adults with moderate to severe system- ic lupus erythematosus (SLE) who are receiving standard therapy.
The FDA had approved anifrolumab-fnia injection (Saphnelo; AstraZeneca) for the treatment of adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy.
The approval carries the limitation that the efficacy of Saphnelo has not been evaluated in patients with severe active central nervous system lupus or severe active lupus nephritis and is not recommended in these situations.1 Symptoms of SLE include fatigue, fevers, joint swelling, pain, and rashes. Approximately 5 million individuals worldwide have a form of lupus, and more than half of those with SLE develop permanent organ damage.2
Pharmacology and Pharmacokinetics
Saphnelo is a fully human IgG1ҡ monoclonal antibody that binds to subunit 1 of the type 1 interferon-α/β receptor (IFNAR) with high affinity and specificity, which causes the biologic activity of type 1 IFNs to be blocked. Saphnelo also reduces the levels of cell surface IFNAR1 available for receptor assembly. By blocking receptor-mediated type 1 IFN signaling, IFN- responsive gene expression and downstream inflammatory and immunological processes are inhibited. Type 1 IFN inhibition also blocks plasma cell differentiation and normalizes peripheral T-cell subsets. Type 1 IFNs are involved in the pathogenesis of SLE, with approximately 60% to 80% of adults with active SLE demonstrating elevated levels of type 1 IFN inducible genes.1,2
Saphnelo displays nonlinear pharmacokinetics. Steady-state plasma concentration is observed by day 85, and the estimated systemic clearance is 0.193 L/day.1
Dosage and Administration
The recommended dose of Saphnelo is 300 mg administered as a 30-minute intravenous infusion every 4 weeks. It is supplied as a 300-mg/2 mL solution in a single-dose vial. Saphnelo requires dilution prior to administration.1
Saphnelo was evaluated in 3 double-blind, multicenter, placebo-controlled, randomized studies in adults with moderate to severe SLE who were receiving standard therapy. In trial 1, 305 patients were randomized 1:1:1 to receive Saphnelo 300 mg, Saphnelo 1000 mg, or a placebo for up to 52 weeks. The primary end point was a combined assessment of the SLE Responder Index (SRI-4) and the sustained reduction in oral corticosteroid use at week 24. Both groups receiving Saphnelo showed improvement compared with those using the placebo.
Trial 2 randomized 457 patients 1:2:2 to receive Saphnelo 150 mg, Saphnelo 300 mg, or a placebo. The primary end point was improvement in disease activity as measured by SRI-4 at week 52, which the trial did not meet.
In trial 3, 362 patients were randomized 1:1 to receive Saphnelo 300 mg
or a placebo. The primary end point was improvement in disease activity as assessed by the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at week 52. The trial found Saphnelo to be more effective than the placebo.1,2
Contradictions, Warnings, and Precautions
Treatment with Saphnelo is contraindicated in patients with a history of anaphylaxis to the medication.
Patients using Saphnelo have experienced serious and sometimes fatal infections. In controlled trials, Saphnelo increased the risk of herpes zoster and respiratory infections. The medication should not be initiated in patients with an active infection, and the individual benefits and risks should be considered in patients with a chronic or severe infection. Interruption of treatment should be considered if a new infection occurs. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported after administration of Saphnelo.
If a serious hypersensitivity or infusion-related reaction occurs, the infusion of Saphnelo should be stopped immediately and appropriate therapy initiated. Because there is an increased risk of malignancies with the use of immunosuppressants, the individual benefits and risks in patients with known risk factors for malignancy should be considered before beginning treatment. The concomitant use of live or live-attenuated vaccines should be avoided. The combination of Saphnelo and other biologic therapies has not been evaluated and is not recommended.
The most common adverse reactions are bronchitis, cough, herpes zoster, infusion-related reactions, nasopharyngitis, and upper respiratory tract infections.1
Monica Holmberg, PharmD, BCPS, is a pharmacist and Pharmacy Times® contributor.
1. Saphnelo. Prescribing information. AstraZeneca Pharmaceuticals LP; 2021. Accessed September 29, 2021. https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/44b6985c-8268-46b1-ba3e-2bb43bfd4d4c/44b6985c-8268-46b1-ba3e-2bb43bfd4d4c_viewable_rendition__v.pdf
2. Saphnelo(anifrolumab)approvedintheUSfor moderate to severe systemic lupus erythematosus. News release. AstraZeneca. August 2, 2021. Accessed September 29, 2021. https:// www.astrazeneca-us.com/content/az-us/media/ press-releases/2021/saphnelo--anifrolumab--approved-in-the-us-for-moderate-to-severe.html