Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect most organs of the body. The skin and the musculoskeletal system are organs that are frequently affected in individuals with SLE. The disease is characterized by intermittent flares. These flares can cause increased organ damage as well as decrease the quality of life for the individual with SLE. Standard therapies used to treat SLE can include antimalarial drugs (e.g., hydroxychloroquine, chloroquine), glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), and immunosuppressants (e.g., azathioprine, methotrexate). The medications used to treat SLE and the flares can also cause organ damage that is separate from the damage caused by the disease itself. One of the goals of providers of care for individuals with SLE is to taper off glucocorticoids to the lowest dose that will prevent flares since the corticosteroids can cause organ damage and other undesirable side effects.
Anifrolumab (Saphnelo) is a human immunoglobulin (Ig) G1 kappa monoclonal antibody that binds to subunit 1 of the type I interferon (IFN) receptor (IFNAR) with high specificity and affinity. This binding inhibits type I IFN signaling, thereby blocking the biologic activity of type I IFNs. Anifrolumab (Saphnelo) also induces the internalization of IFNAR1, thereby reducing the levels of cell surface IFNAR1 available for receptor assembly. Blockade of receptor-mediated type I IFN signaling inhibits IFN responsive gene expression as well as downstream inflammatory and immunological processes. Inhibition of type I IFN blocks plasma cell differentiation and normalized peripheral T-cell subsets.
PEER-REVIEWED LITERATURE
Summary
The safety and efficacy of anifrolumab (Saphnelo) was evaluated in a phase IIb, randomized, double-blind, parallel group, placebo-controlled clinical trial (Furie et al., 2017) including 305 individuals with moderate-to-severe SLE. Ninety-nine individuals received anifrolumab (Saphnelo) 300 mg, 104 individuals received anifrolumab (Saphnelo) 1000 mg, and 102 individuals received placebo. All participants received the study drug by intravenous infusion (IV) every 4 weeks and continued to receive standard therapy. The length of the study was 48 weeks. Tapering of the individuals' oral corticosteroid (OC) dose was encouraged but was left to the discretion of the investigator at the site. The primary endpoint was the percentage of individuals achieving an SLE Responder Index (SRI) response at week 24 as well as maintaining a reduction of their OC dose to less than 10 mg/d and less than or equal to the dose at week 1 from weeks 12 through 24. The primary endpoint was reached by 34.3 percent of the 99 individuals receiving the 300-mg dose (P=0.014) and 28.8 percent of the individuals receiving the 1000-mg dose (P=0.063), but only 17.6 percent of individuals receiving placebo.
The safety and efficacy of anifrolumab (Saphnelo) was evaluated in a phase III, randomized, double-blind, parallel group, placebo-controlled clinical trial (Furie et al., 2019) including 457 individuals with moderate-to-severe SLE. One hundred eighty individuals received anifrolumab (Saphnelo) 300 mg, 93 individuals received anifrolumab (Saphnelo) 150 mg, and 184 individuals received placebo. All participants received the study drug by IV every 4 weeks and continued to receive standard therapy. The length of the study was 48 weeks. There were standard mandatory attempts at tapering of the participants' OCs if the individual was receiving a dose equivalent to 10 mg/d or more of prednisone at baseline starting at week 8 through week 40. The primary endpoint was the difference between the percentage of individuals achieving a SRI-4 response at week 52 with anifrolumab (Saphnelo) 300 mg versus placebo. Some of the secondary endpoints included the percentage of individuals who were able to taper and maintain their OC dose to 7.5 mg/d or less from week 40 through to week 52; the percentage of individuals with a cutaneous lupus erythematosus disease area and severity index (CLASI) activity score of 1 or more at baseline who were able to achieve a 50 percent or more decrease in their CLASI score by the 12th week; the percentage of individuals who reached SRI-4 by week 24; and the annualized flare rate total through the 52nd week. The primary endpoint was not achieved as only 35 percent of the anifrolumab (Saphnelo) 300 mg group and 40 percent of the placebo group achieved a SRI-4 response by week 52. However, 41 percent of the anifrolumab (Saphnelo) 300-mg group versus 32 percent of the placebo group were able to decrease and maintain their OC dose to 7.5 mg/d or less and the percentage of individuals who achieved at least 50 percent reduction of their CLASI score by the 12th week was 42 percent in the anifrolumab (Saphnelo) 300 mg group versus 25 percent in the placebo group. The annualized flare rates were also not significant at 0.60 for the anifrolumab (Saphnelo) group versus 0.72 for the placebo group.
The safety and efficacy of anifrolumab (Saphnelo) was evaluated in another phase III, randomized, double-blind, parallel group, placebo-controlled clinical trial (Morand et al., 2020) using a different primary endpoint. For this study, the primary endpoint was the difference in the proportion of individuals in a group receiving the study drug versus a group receiving placebo in response at week 52 in their British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) responses. The BICLA response was assessed by all of the following: a decrease in all severe or moderately severe disease activity from the individual's baseline to reassessment, no worsening in other organ systems or disease activity, no discontinuation of the trial protocols, and no use of restricted drugs beyond levels allowed in the trial's protocols. The secondary endpoints were a BICLA response in individuals who were identified as having a high IFN gene signature at baseline, decrease in OC dosage, decrease by 50 percent or more in the CLASI score by week 12, decrease by 50 percent or more in the swollen/tender joints count by week 52, and the annualized flare rate. Individuals with moderate to severe SLE were randomly assigned to receive anifrolumab (Saphnelo) 300 mg (180 individuals) or placebo (182 individuals) IV every 4 weeks for 48 weeks. The individuals continued to receive standard therapy for SLE and there was a mandatory attempt to taper the OC dose after 8 weeks through week 40 if the individual was on a prednisone-equivalent dose of 10 mg/d or more. The proportion of individuals who had a BICLA response at week 52 in the anifrolumab (Saphnelo) group was 47.8 percent versus 31.5 percent in the placebo group (P=0.001). For the subpopulation of individuals with a high IFN, 48.0 percent in the anifrolumab (Saphnelo) group and 30.7 percent in the placebo group had a BICLA response at week 52 (P=0.002). The proportion of individuals able to decrease and sustain a lower OC dose was 47.0 percent in the anifrolumab (Saphnelo) group and 30.2 percent in the placebo group (P=0.01). The proportion of individuals able to decrease their CLASI score by 50 percent or more was 49.0 percent in the anifrolumab (Saphnelo) group and 25.0 percent in the placebo group (P=0.04). The proportion of individuals with a decrease by 50 percent or more in the swollen/tender joint count was 42.2 percent in the anifrolumab (Saphnelo) and 37.5 percent in the placebo group (P=0.55). The annualized flare rate was 0.43 in the anifrolumab (Saphnelo) group and 0.64 in the placebo group (P=0.08).
OFF-LABEL INDICATIONS
There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
