Regulatory Decision Summary for Saphnelo

Systemic lupus erythematosus (SLE) is a chronic, debilitating, autoimmune, rheumatic disease. It is complex and multi-systemic, potentially affecting all organ systems. Manifestations and progression of SLE are unpredictable and range in severity from mild to life-threatening. SLE patients are at an increased risk for serious comorbidities, long-term morbidity, and have a higher mortality rate the general population. There remains an unmet medical need for additional targeted therapies for the management of SLE.

Authorization of Saphnelo was based on three multicentre, randomized, double-blind, placebo-controlled studies, each with a 52 week treatment period. Patients with active, autoantibody positive, SLE received either anifrolumab 300 mg administered via intravenous infusion or placebo every 4 weeks for a total of 13 doses in addition to their standard SLE therapy.

The benefits of Saphnelo are demonstrated by an assessment of clinical response using two valid composite endpoints that measure overall disease activity in different ways: SRI-4 (Systemic Lupus Erythematosus Responder Index of ≥4) and BICLA (British Isles Lupus Assessment Group-2004-based Combined Lupus Assessment). In one study, where SRI-4 was evaluated as the primary endpoint, a treatment benefit for anifrolumab compared to placebo was not observed. However, a positive treatment effect in favour of Saphnelo was observed in the other two studies, where SRI-4 response was evaluated as a secondary endpoint. When BICLA was evaluated as a measure of overall disease activity, a consistent treatment effect in favour of Saphnelo was observed for BICLA response in all three studies.

Despite uncertainties surrounding the inconsistent SRI-4 response observed in one of the studies, when considering the totality of evidenced presented in all three studies, a favourable treatment effect for Saphnelo was consistently observed for several clinically meaningful endpoints, including positive treatment effects on concomitant corticosteroid use and annualized flare rate.

The most common treatment-emergent adverse events reported in ≥5% of patients during treatment with Saphnelo included nasopharyngitis (16.3%, placebo: 9.4%), upper respiratory tract infection (15.5%, placebo: 9.7%), urinary tract infection (12.0%, placebo: 13.5%), bronchitis (9.8%, placebo: 4.3%), infusion related reaction (9.4%, placebo: 7.1%), headache (8.1%, placebo: 9.7%), herpes zoster (6.1%, placebo: 1.3%), back pain (5.2%, placebo: 4.3%), sinusitis (5.2%, placebo: 5.2%) and cough (5.0%, placebo: 3.2%).

The recommended dose of Saphnelo is 300 mg, administered as an intravenous infusion over a 30 minute period, every 4 weeks.

Overall, the anticipated benefits of Saphnelo are expected to outweigh its risks when used under the conditions of use recommended in the Saphnelo (anifrolumab for injection) product monograph at this time.

For more information on Health Canadas decision, please view the Summary Basis of Decision.