ENFLONSIA

Clesrovimab-cfor is a respiratory syncytial virus F protein-directed fusion inhibitor. Clesrovimab-cfor is a fully human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody produced in recombinant Chinese hamster ovary (CHO) cells. The molecular weight is approximately 149 kDa. ENFLONSIA (clesrovimab-cfor) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution for intramuscular injection. Each 0.7 mL contains 105 mg of clesrovimab-cfor, arginine hydrochloride (10.33 mg), histidine (0.55 mg), L-histidine monohydrochloride monohydrate (0.74 mg), polysorbate 80 (0.14 mg), sucrose (35 mg) and water for injection (USP). The pH is 6.0.

ENFLONSIA is indicated for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants who are born during or entering their first RSV season. ENFLONSIA is a respiratory syncytial virus (RSV) F protein-directed fusion inhibitor indicated for the prevention of RSV lower respiratory tract disease in neonates and infants who are born during or entering their first RSV season. ( 1 )

Recommended dosage: 105 mg administered as a single intramuscular (IM) injection. ( 2.1 ) 2.1 Recommended Dosage The recommended dose for neonates and infants born during or entering their first RSV season is 105 mg administered as a single intramuscular (IM) injection. For neonates and infants born during the RSV season, administer ENFLONSIA once starting from birth. For infants born outside the RSV season, administer ENFLONSIA once prior to the start of their first RSV season considering the duration of protection provided by ENFLONSIA [see Clinical Pharmacology (12.2) ]. Infants Undergoing Cardiac Surgery with Cardiopulmonary Bypass For infants undergoing cardiac surgery with cardiopulmonary bypass during or entering their first RSV season, an additional 105 mg dose administered as an IM injection is recommended as soon as the infant is stable after surgery to ensure adequate clesrovimab-cfor serum levels. 2.2 Administration Instructions ENFLONSIA must be administered by a healthcare provider. Before injection, remove ENFLONSIA from the refrigerator and allow the prefilled syringe to come to room temperature for approximately 15 minutes. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. ENFLONSIA is a clear to slightly opalescent, colorless to slightly yellow solution. This product should not be used if particulate matter or discoloration is found. Do not use if the prefilled syringe has been dropped or damaged, the security seal on the carton has been broken, or the expiration date has passed. Refer to Figure 1 for prefilled syringe components. Figure 1: Prefilled Syringe Components Step 1: Hold the syringe barrel in one hand and unscrew the tip cap by twisting it counter-clockwise with the other hand. Do not remove the Luer Lock adaptor and the finger flange extender. Step 2: Attach a sterile Luer Lock needle by twisting in a clockwise direction until the needle fits securely on the syringe. Due to the viscosity of the product, use a 22- to 25-gauge needle. Step 3: Inject the entire contents of the ENFLONSIA prefilled syringe intramuscularly in the anterolateral aspect of the thigh. ENFLONSIA should not be injected in the gluteal area or areas where there may be a major nerve trunk and/or blood vessel. Step 4: Discard syringe into a sharps container. Co-administration with Childhood Vaccines and Immunoglobulin Products ENFLONSIA can be given concomitantly with childhood vaccines [see Clinical Pharmacology (12.3) ] . When ENFLONSIA is administered concomitantly with injectable vaccines, it should be given using a separate syringe and at a different injection site. Do not mix ENFLONSIA with any vaccines or medications in the same syringe or vial. There is no information regarding co-administration of ENFLONSIA with other immunoglobulin products. There are no data regarding substitution of ENFLONSIA for palivizumab once prophylaxis treatment is initiated with palivizumab for the RSV season. Prefilled Syringe

ENFLONSIA is contraindicated in infants with a history of serious hypersensitivity reactions, including anaphylaxis, to any component of ENFLONSIA [see Warnings and Precautions (5.1) and Description (11) ]. ENFLONSIA is contraindicated in infants with a history of serious hypersensitivity reactions, including anaphylaxis, to any component of ENFLONSIA. ( 4 )

Most common adverse reactions were injection-site erythema (3.8%), injection-site swelling (2.7%) and rash (2.3%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of ENFLONSIA was evaluated in 2,858 infants who received ENFLONSIA in Phase 2b/3 and Phase 3 clinical trials (Trial 004 and Trial 007). Neonates and Infants Entering Their First RSV Season (Trial 004) Trial 004 was a Phase 2b/3, randomized, double-blind placebo-controlled, multisite trial conducted in early and moderate preterm infants (≥29 to <35 weeks gestational age (GA)) and late preterm and full-term infants (≥35 weeks GA). Participants were randomized 2:1 and received a single 105 mg dose of ENFLONSIA (N=2,412, including 422 early and moderate preterm infants) or saline placebo (N=1,202, including 209 early and moderate preterm infants) by IM injection. Participants were monitored for 30 minutes post-dose. Safety was assessed using an electronic diary device from Days 1 through 42 post-dose. Participants were monitored for serious adverse events (SAEs) through the duration of their participation for up to 365 days post-dose. A subset of participants was monitored for SAEs for up to 515 days post-dose. Table 1 summarizes the adverse reactions in participants who received ENFLONSIA. Most (≥97%) of the adverse reactions were toxicity grade 1 (mild) or grade 2 (moderate). Table 1: Adverse Reactions Reported at an Incidence Higher Than Placebo (Trial 004) Adverse Reaction ENFLONSIA N=2,412 Sample size reflects the number of participants included in the safety analysis population. % Placebo N=1,202 % Injection-site erythema Solicited on Day 1 through Day 5 post-dose using an electronic diary device. (occurring within 5 days post-dose) 3.8 3.3 Injection-site swelling (occurring within 5 days post-dose) 2.7 2.6 Rash Defined by the following grouped preferred terms: rash, rash erythematous, rash macular, rash papular, rash maculo-papular, rash vesicular, rash exfoliative, dermatitis allergic, drug eruption and toxic skin eruption. (occurring within 14 days post-dose) 2.3 1.9 Infants Born at ≤35 Weeks Gestational Age and Infants with Chronic Lung Disease (CLD) of Prematurity or Hemodynamically Significant Congenital Heart Disease (CHD) Entering Their First RSV Season (Trial 007) Trial 007 was a Phase 3, randomized, partially-blind, palivizumab-controlled, multisite trial conducted in infants at increased risk of severe RSV disease. Participants were randomized and received a single 105 mg dose of ENFLONSIA (N=446) followed by a dose of placebo one month later or 3 to 5 monthly doses of 15 mg/kg palivizumab (N=450) by IM injection. Of the 446 participants who received ENFLONSIA, 176 had CLD of prematurity or CHD and 270 were early or moderate preterm infants (≤35 weeks GA) without CLD of prematurity or CHD. Participants were monitored for 30 minutes post-dose. Safety was assessed using an electronic diary device from Day 1 (dose 1) through 14 days post-dose 2, and 14 days after each subsequent dose. Participants were monitored for serious adverse events in the first RSV season for up to 365 days. The safety profile of ENFLONSIA in infants at increased risk of severe RSV disease entering their first season was similar to palivizumab and consistent with the safety profile of ENFLONSIA in infants in Trial 004.

7.1 Interference with Rapid Antigen Detection RSV Diagnostic Assays Clesrovimab-cfor may interfere with some immunologically-based RSV diagnostic assays (i.e., rapid antigen tests) as observed in laboratory studies. Confirmation using an RT-PCR assay is recommended when rapid antigen RSV diagnostic assay results are negative and clinical observations are consistent with RSV infection. Clesrovimab-cfor does not interfere with RT-PCR diagnostic assays [see Warnings and Precautions (5.2) ] .

Storage and Handling Store prefilled syringes under refrigeration at 36°F to 46°F (2°C to 8°C). Keep the prefilled syringe in the original carton to protect from light until time of use. ENFLONSIA may be kept at room temperature between 68°F to 77°F (20°C to 25°C) for a maximum of 48 hours. After removal from the refrigerator, ENFLONSIA must be used within 48 hours or discarded. Do not freeze. Do not shake.