SAPHNELO (anifrolumab-fnia) is indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE), who are receiving standard therapy

The efficacy of SAPHNELO has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Use of SAPHNELO is not recommended in these situations.

Injection: 300 mg/2 mL (150 mg/mL) as a clear to opalescent, colorless to slightly yellow, solution in a single-dose vial.

SAPHNELO is contraindicated in patients with a history of anaphylaxis with anifrolumab-fnia

The following clinically significant adverse reactions are also discussed elsewhere in the labeling:

No formal drug interaction studies have been conducted.

Anifrolumab-fnia is a type I interferon (IFN) receptor antagonist, immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that is produced in mouse myeloma cells (NS0) by recombinant DNA technology. The molecular weight is approximately 148 kDa.

SAPHNELO (anifrolumab-fnia) injection is a sterile, preservative‑free, clear to opalescent, colorless to slightly yellow, solution for intravenous use. SAPHNELO contains anifrolumab-fnia at a concentration of 150 mg/mL in a single-dose vial.

Each vial contains 300 mg (150 mg/mL) of anifrolumab-fnia, L-histidine (3 mg), L-histidine hydrochloride monohydrate (6 mg), L-lysine hydrochloride (18 mg), polysorbate 80 (1 mg), trehalose dihydrate (98 mg), and Water for Injection, USP. The pH is 5.9.

The safety and efficacy of SAPHNELO were evaluated in three 52-week treatment period, multicenter, randomized, double-blind, placebo-controlled studies (Trial 1 [NCT01438489], Trial 2 [NCT02446912] and Trial 3 [NCT02446899]). Patients were diagnosed with SLE according to the American College of Rheumatology (1982 revised) classification criteria. All patients were ≥18 years of age and had moderate to severe disease, with a SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥6 points, organ level involvement based on BILAG assessment, and a Physician’s Global Assessment [PGA] score ≥1, despite receiving standard SLE therapy consisting of either one or any combination of oral corticosteroids (OCS), antimalarials and/or immunosuppressants at baseline. Patients continued to receive their existing SLE therapy at stable doses during the clinical trials, with the exception of OCS (prednisone or equivalent) where tapering was a component of the protocol. Patients who had severe active lupus nephritis and patients who had severe active central nervous system lupus were excluded. The use of other biologic agents and cyclophosphamide were not permitted during the trials; patients receiving other biologic therapies were required to complete a wash-out period of at least 5 half‑lives prior to enrollment. All three studies were conducted in North America, Europe, South America and Asia. Patients received anifrolumab-fnia or placebo, administered by intravenous infusion, every 4 weeks.

Efficacy of SAPHNELO was established based on assessment of clinical response using the composite endpoints, the British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA) and the SLE Responder Index (SRI‑4).

BICLA response at Week 52, was defined as improvement in all organ domains with moderate or severe activity at baseline:

SRI‑4 response, was defined as meeting each of the following criteria at Week 52 compared with baseline:

Trial 1 randomized 305 patients (1:1:1) who received anifrolumab-fnia, 300 mg or 1000 mg, or placebo for up to 52 weeks. The primary endpoint was a combined assessment of the SRI-4 and the sustained reduction in OCS (<10 mg/day and ≤OCS dose at week 1, sustained for 12 weeks) measured at Week 24.

Trial 2 and 3 were similar in design. Trial 2 randomized 457 patients who received anifrolumab-fnia 150 mg, 300 mg or placebo (1:2:2). Trial 3 randomized 362 patients (1:1) who received anifrolumab-fnia 300 mg or placebo. The primary endpoints were improvement in disease activity evaluated at 52 weeks, measured by SRI‑4 in Trial 2 and BICLA in Trial 3 (defined above). The common secondary efficacy endpoints included in both studies were the maintenance of OCS reduction, improvement in cutaneous SLE activity, and flare rate. During Weeks 8-40, patients with a baseline OCS ≥10 mg/day were required to taper their OCS dose to ≤7.5 mg/day, unless there was worsening of disease activity. Both studies evaluated the efficacy of anifrolumab-fnia 300 mg versus placebo; a dose of 150 mg was also evaluated for dose-response in Trial 2.

Patient demographics and disease characteristics were generally similar and balanced across treatment arms (Table 2).

Randomization was stratified by disease severity (SLEDAI-2K score at baseline, <10 vs ≥10 points), OCS dose on Day 1 (<10 mg/day vs ≥10 mg/day prednisone or equivalent) and interferon gene signature test results (high vs low).

The reduction in disease activity seen in the BICLA and SRI-4 was related primarily to improvement in the mucocutaneous and musculoskeletal organ systems. Flare rate was reduced in patients receiving SAPHNELO compared to patients who received placebo although the difference was not statistically significant.

In Trial 3, examination of subgroups by age, race, gender, ethnicity, disease severity [SLEDAI-2K at baseline], and baseline OCS use did not identify differences in response to anifrolumab-fnia.

Figure 1 shows the proportion of BICLA responders through the 52-week treatment period in Trial 3.

SAPHNELO (anifrolumab-fnia) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution for intravenous infusion. It is packaged in a 2 mL clear glass vial containing 300 mg/2 mL (150 mg/mL) of anifrolumab-fnia.

SAPHNELO is available in a carton containing one single-dose vial (NDC-0310-3040-00).

Store in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light.

Do not freeze. Do not shake.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Inform patients that SAPHNELO may decrease their ability to fight infections, and that serious infections, including fatal ones, occurred in patients receiving SAPHNELO in clinical trials. Also inform patients that they are at increased risk of respiratory infections and herpes zoster during treatment with SAPHNELO

Inform patients that serious hypersensitivity reactions, including anaphylaxis, have been reported in patients who received SAPHNELO. Instruct patients to immediately tell their healthcare provider or go to the emergency department of their nearest hospital, if they experience symptoms of an allergic reaction (e.g., anaphylaxis) during or after the administration of SAPHNELO

Inform patients that they should not receive live or live-attenuated vaccines while receiving SAPHNELO. Advise patients to discuss with their healthcare provider before seeking immunizations on their own

Advise female patients to inform their healthcare provider if they intend to become pregnant during therapy, suspect they are pregnant or become pregnant while receiving SAPHNELO

Inform women that they can find information about a pregnancy exposure registry which monitors pregnancy outcomes in women exposed to SAPHNELO by calling AstraZeneca at 1-877-693-9268.

Manufactured by: AstraZeneca AB Södertälje, Sweden SE-15185

US License No. 2059

Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850

©AstraZeneca 2024

NDC 0310-3040-00                              

(anifrolumab-fnia)

Injection

300 mg/2 mL

(150 mg/mL)

For Intravenous Infusion After Dilution

Must dilute before use. See prescribing information.

Single-dose vial. Discard unused portion.

Store refrigerated at 2°C to 8°C (36°F to 46°F).

Keep vial in original carton to protect from light.

Do not shake or freeze.

1 single-dose vial

AstraZeneca