ENFLONSIA

5 WARNINGS AND PRECAUTIONS Hypersensitivity Including Anaphylaxis: Serious hypersensitivity reactions, including anaphylaxis, have been observed with other human immunoglobulin G1 (IgG1) monoclonal antibodies. Initiate appropriate medications and/or supportive care if such reactions occur. ( 5.1 ) 5.1 Hypersensitivity Including Anaphylaxis Serious hypersensitivity reactions, including anaphylaxis, have been observed with other human immunoglobulin G1 (IgG1) monoclonal antibodies. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, initiate appropriate medications and/or supportive therapy. 5.2 RSV Diagnostic Test Interference Clesrovimab-cfor may interfere with some immunologically-based RSV diagnostic assays (i.e., rapid antigen tests) as observed in laboratory studies. Confirmation using a reverse transcriptase polymerase chain reaction (RT-PCR) assay is recommended when rapid antigen assay results are negative and clinical observations are consistent with RSV infection [see Drug Interactions (7.1) ].

6 ADVERSE REACTIONS 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.

<table width="85%" ID="t1"><caption>Table 1: Adverse Reactions Reported at an Incidence Higher Than Placebo (Trial 004)</caption><col width="40%" align="left" valign="top"/><col width="30%" align="center" valign="top"/><col width="30%" align="center" valign="top"/><thead><tr styleCode="Botrule"><th styleCode="Lrule Rrule">Adverse Reaction</th><th styleCode="Rrule">ENFLONSIA N=2,412<footnote ID="t1f1">Sample size reflects the number of participants included in the safety analysis population.</footnote> %</th><th styleCode="Rrule">Placebo N=1,202<footnoteRef IDREF="t1f1"/> %</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Rrule Lrule">Injection-site erythema<footnote ID="t1f2">Solicited on Day 1 through Day 5 post-dose using an electronic diary device.</footnote> (occurring within 5 days post-dose)</td><td styleCode="Rrule">3.8</td><td styleCode="Rrule">3.3</td></tr><tr styleCode="Botrule"><td styleCode="Rrule Lrule">Injection-site swelling<footnoteRef IDREF="t1f2"/> (occurring within 5 days post-dose)</td><td styleCode="Rrule">2.7</td><td styleCode="Rrule">2.6</td></tr><tr styleCode="Botrule"><td styleCode="Rrule Lrule">Rash<footnote ID="t1f3">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.</footnote> (occurring within 14 days post-dose)</td><td styleCode="Rrule">2.3</td><td styleCode="Rrule">1.9</td></tr></tbody></table>