SAPHNELO (anifrolumab-fnia)

SAPHNELO (anifrolumab-fnia) injection

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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.

Indications and usage

SAPHNELO is a type I interferon (IFN) receptor antagonist indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE), who are receiving standard therapy.

Limitations of Use: 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.

Dosage and administration

SAPHNELO must be diluted prior to intravenous administration.

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

Missed dose: If a planned infusion is missed, administer SAPHNELO as soon as possible. Maintain a minimum interval of 14 days between infusions.

Instructions for Preparation and Administration

SAPHNELO is supplied as a single-dose vial. Prepare the diluted infusion solution using aseptic technique, by the following procedure:

  1. Visually inspect the vial for particulate matter and discoloration. SAPHNELO is a clear to opalescent, colorless to slightly yellow, solution. Discard the vial if the solution is cloudy, discolored or visible particles are observed. Do not shake the vial.
  2. Withdraw and discard 2 mL of solution from a 100 mL 0.9% Sodium Chloride Injection, USP infusion bag.
  3. Withdraw 2 mL of solution from the vial of SAPHNELO and add it to the infusion bag. Mix the solution by gentle inversion. Do not shake.
  4. Each vial is intended for one time use only. Discard any unused portion remaining in the vial.
  5. Administer the infusion solution immediately after preparation.
  6. If the infusion solution is not administered immediately, store the diluted solution of SAPHNELO at room temperature (59°F to 77°F, 15°C to 25°C) for up to 4 hours, or refrigerated (36°F to 46°F, 2°C to 8°C) for up to 24 hours. Do not freeze. Protect from light. If refrigerated, allow the diluted SAPHNELO solution to reach room temperature prior to administration.
  7. Administer the infusion solution intravenously over a 30-minute period through an infusion line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter.
  8. Upon completion of the infusion, flush the infusion set with 25 mL of 0.9% Sodium Chloride Injection, USP to ensure that all of the solution for infusion has been administered.
  9. Do not co-administer other medicinal products through the same infusion line.
  10. Dispose of any unused medicinal product or waste material in accordance with local requirements.

Mechanism of Action

Anifrolumab-fnia is a human IgG1κ monoclonal antibody that binds to subunit 1 of the type I interferon receptor (IFNAR) with high specificity and affinity. This binding inhibits type I IFN signaling, thereby blocking the biologic activity of type I IFNs. Anifrolumab-fnia 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 normalizes peripheral T-cell subsets.

Type I IFNs play a role in the pathogenesis of SLE. Approximately 60-80% of adult patients with active SLE express elevated levels of type I IFN inducible genes.

Pharmacodynamics

In patients with SLE, following the administration of anifrolumab-fnia at 300 mg dose, via intravenous infusion every 4 weeks for 52 weeks, neutralization (≥80%) of a type I IFN gene signature was observed from Week 4 to Week 52 in blood samples of patients with elevated levels of type I IFN inducible genes and returned to baseline levels within 8 to 12 weeks fol lowing withdrawal of anifrolumab-fnia at the end of the 52-week treatment period. However, the clinical relevance of the type I IFN gene signature neutralization is unclear.

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In SLE patients with positive anti-dsDNA antibodies at baseline (Trials 2 and 3), treatment with anifrolumab-fnia 300 mg led to numerical reductions in anti-dsDNA antibodies over time through Week 52.

In patients with low complement levels (C3 and C4), increases in complement levels were observed in patients receiving anifrolumab-fnia through Week 52.

Pharmacokinetics

The PK of anifrolumab-fnia was studied in adult patients with SLE following intravenous doses ranging from 100 to 1000 mg once every 4 weeks, and healthy volunteers following a single intravenous dose at 300 mg. Anifrolumab-fnia exhibits non-linear PK in the dose range of 100 mg to 1000 mg with more than dose-proportional increases in the exposure as measured by AUC. Following the 300 mg every 4 weeks intravenous administrations of anifrolumab-fnia, steady-state was reached by Day 85. The accumulation ratio was approximately 1.36 for Cmax and 2.49 for Ctrough.

Distribution: Based on population PK analysis, the estimated volume of distribution at steady state for a typical patient with SLE (69.1 kg) is 6.23 L.

Elimination: From population PK analysis, anifrolumab-fnia exhibited non-linear PK due to IFNAR1-mediated drug clearance.

Following the administration of anifrolumab-fnia at a dose of 300 mg via intravenous infusion every 4 weeks, the estimated systemic clearance (CL) for anifrolumab-fnia was 0.193 L/day.

Warning and precautions

Serious Infections: Serious and sometimes fatal infections have occurred in patients receiving immunosuppressive agents, including SAPHNELO.

Consider the benefit and risk of administering SAPHNELO in patients with a chronic infection, a history of recurrent infections, or known risk factors for infection. Avoid initiating treatment with SAPHNELO in patients with any clinically significant active infection until the infection resolves or is adequately treated. Instruct patients to seek medical advice if signs or symptoms of clinically significant infection occur. If a patient develops an infection, or is not responding to standard anti-infective therapy, monitor the patient closely and consider interrupting SAPHNELO therapy until the infection resolves.

Hypersensitivity Reactions Including Anaphylaxis: Serious hypersensitivity reactions (including anaphylaxis) have been reported following SAPHNELO administration. Events of angioedema have also been reported.

SAPHNELO should be administered by healthcare providers prepared to manage hypersensitivity reactions, including anaphylaxis, and infusion-related reactions. If a serious infusion-related or hypersensitivity reaction (e.g., anaphylaxis) occurs, immediately interrupt the administration of SAPHNELO and initiate appropriate therapy.

Malignancy: There is an increased risk of malignancies with the use of immunosuppressants. The impact of SAPHNELO treatment on the potential development of malignancies is not known.

Consider the individual benefit-risk in patients with known risk factors for the development or reoccurrence of malignancy prior to prescribing SAPHNELO. In patients who develop malignancies, consider the benefit-risk of continued treatment with SAPHNELO.

Immunization: Update immunizations, according to current immunization guidelines, prior to initiating SAPHNELO therapy. Avoid concurrent use of live or live-attenuated vaccines in patients treated with SAPHNELO.

Not Recommended for Concomitant Use with Other Biologic Therapies: SAPHNELO has not been studied in combination with other biologic therapies, including B-cell-targeted therapies. Therefore, use of SAPHNELO is not recommended for use in combination with biologic therapies.

Use in specific populations

Pregnancy: The limited human data with SAPHNELO use in pregnant women are insufficient to inform on drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcome. Monoclonal IgG antibodies are known to be actively transported across the placenta as pregnancy progresses; therefore, anifrolumab-fnia exposure to the fetus may be greater during the third trimester of pregnancy.

Lactation: No data are available regarding the presence of SAPHNELO in human milk, the effects on the breastfed child, or the effects on milk production. Anifrolumab-fnia was detected in the milk of female cynomolgus monkeys administered anifrolumab-fnia. Due to species-species differences in lactation physiology, animal data may not reliably predict drug levels in humans. Maternal IgG is known to be present in human milk. If anifrolumab-fnia is transferred into human milk, the effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to anifrolumab-fnia are unknown

Pediatric Use: The safety and efficacy of SAPHNELO in pediatric patients less than 18 years of age have not been established.

Geriatric Use: Of the 664 patients with SLE exposed to anifrolumab-fnia in clinical trials, 3% (n=20) were 65 and over. The number of patients aged 65 years of age and older was not sufficient to determine whether they respond differently from younger adult patients.

Storage and handling

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.

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