Enflonsia Drug Information

Description of Clinical Trials

The efficacy and safety of ENFLONSIA were evaluated in preterm and full-term infants in the trials summarized in Table 2. Table 2: Trials Conducted with ENFLONSIA for the Prevention of Medically Attended RSV Lower Respiratory Tract Disease Trial Study Population Study Arms Participants randomized and treated GA=gestational age; CLD=chronic lung disease; CHD=hemodynamically significant congenital heart disease Trial 004 (NCT04767373) Infants born at ≥29 weeks GA from birth up to 1 year entering their first RSV season. ENFLONSIA (N=2,411) Placebo (N=1,203) 1 participant was randomized to placebo but received ENFLONSIA Trial 007 (NCT04938830) Infants born at ≤35 weeks GA, or infants with CLD of prematurity or hemodynamically significant CHD from birth up to 1 year entering their first RSV season. ENFLONSIA (N=446) Palivizumab (N=450)

Prevention of

RSV-Associated Disease in Neonates and Infants (≥29 Weeks GA) Entering Their First RSV Season (Trial 004) Trial 004 was a Phase 2b/3, randomized, double-blind placebo-controlled, multi-site trial conducted in 22 countries from the Northern and Southern Hemispheres to evaluate the efficacy of ENFLONSIA in early and moderate preterm infants (≥29 to <35 weeks GA) and late preterm and full-term infants (≥35 weeks GA). The trial assessed the efficacy of ENFLONSIA in the prevention of RSV-associated disease across a spectrum of severity. Participants were randomized 2:1 to receive a single 105 mg dose of ENFLONSIA or saline placebo by IM injection. Among participants who received ENFLONSIA or saline placebo, the median age of infants was 3.1 months (range: 0 to 12 months); 80% were less than 6 months; 16% were greater than or equal to 6 to less than 9 months, 4% were greater than or equal to 9 months of age, and 51% were male.

Of these participants, 18% were GA greater than or equal to 29 weeks and less than 35 weeks, and 82% were GA greater than or equal to 35 weeks. The racial distribution was as follows: 45% were White; 27% were Asian; 14% were Black or African American; 12% were Multi-racial and 2% were American Indian or Alaska Native; 28% were of Hispanic or Latino ethnicity. The primary endpoint was the incidence of RSV-associated Medically Attended Lower Respiratory Infection (MALRI) characterized as cough or difficulty breathing and requiring ≥1 indicator of LRI (wheezing, rales/crackles) or severity (chest wall in-drawing/retractions, hypoxemia, tachypnea, dehydration due to respiratory symptoms) through 150 days after dosing.

Medically Attended (MA) includes all healthcare provider visits in settings such as outpatient clinic, clinical study site, emergency department, urgent care center, and/or hospital. The statistical criterion for success required the lower bound of the 95% CI of efficacy to be greater than 25%. RSV-associated hospitalization through 150 days after dosing was evaluated as a key secondary endpoint. The statistical criterion for success required the lower bound of the 95% CI of efficacy to be greater than 0%. Both efficacy endpoints required an RSV-positive RT-PCR nasopharyngeal (NP) sample.

Table 3 displays efficacy results for the primary and key secondary RSV-associated disease endpoints in preterm and full-term infants from days 1 through 150 post-dose. Table 3: Incidence of RSV-Associated Disease in Infants Born at ≥29 Weeks GA Days 1 Through 150 Post-Dose (Trial 004) RSV-Associated Endpoint ENFLONSIA (n=2,411) Placebo (n=1,203) Efficacy Efficacy for MALRI (requiring ≥1 indicator of LRI or severity) and hospitalization based on relative risk reduction against placebo adjusted for hemisphere at randomization, gestational age group and age group at randomization. (95% CI) Estimate and 95% CI of efficacy were estimated from the modified Poisson regression with robust variance method. Number of cases Incidence Rate over 5 months Number of cases Incidence Rate over 5 months n=Number of participants eligible for inclusion in the full analysis set population.

MALRI (requiring ≥1 indicator of LRI or severity) 60 0.026 74 0.065 60.5% (p<0.001) Hospitalization 9 0.004 28 0.024 84.3%

Prevention of

RSV-Associated Disease in Infants Born at ≤35 Weeks Gestational Age and Infants with CLD of Prematurity or Hemodynamically Significant CHD Entering Their First RSV Season (Trial 007) Trial 007 is a Phase 3, randomized, partially-blind, palivizumab-controlled, multi-site trial conducted in 27 countries from the Northern and Southern Hemispheres to evaluate the efficacy of ENFLONSIA in early (<29 weeks GA) or moderate preterm infants (≥29 to ≤35 weeks GA), and infants with chronic lung disease of prematurity or congenital heart disease of any GA, who are at increased risk for severe RSV disease. Participants were randomized to receive ENFLONSIA or palivizumab by IM injection. Participants randomized to ENFLONSIA received a single 105 mg dose on Day 1 followed by a dose of placebo one month later; 15 mg/kg palivizumab was administered on Day 1 and every month thereafter for a total of 3 to 5 doses.

Among participants who received ENFLONSIA or palivizumab, the median age of infants was 2.5 months (range: 0 to 12 months); 89% were less than 6 months; 9% were greater than or equal to 6 to less than 9 months, 2% were greater than or equal to 9 months of age; and 50% were male. Of these participants, 28% had CLD, 11% had CHD, 6% were GA less than 29 weeks with neither CLD nor CHD and 55% were GA greater than or equal to 29 weeks with neither CLD nor CHD. The racial distribution was as follows: 52% were White; 18% were Asian; 15% were Black or African American; 12% were Multi-racial, and 1% were American Indian or Alaska Native; 32% were of Hispanic or Latino ethnicity. The efficacy of ENFLONSIA in infants at increased risk for severe RSV disease, including preterm infants and infants with chronic lung disease of prematurity or congenital heart disease was established by extrapolation of efficacy of ENFLONSIA from Trial 004 to Trial 007 based on similar pharmacokinetic exposure . The incidence rate of RSV-associated MALRI (requiring ≥1 indicator of LRI or severity) through 150 days after dosing was generally comparable between ENFLONSIA (incidence rate=3.6%, 95% CI: 2.0, 6.0) and palivizumab (incidence rate=2.9%, 95% CI: 1.5, 5.2). The incidence rate of RSV-associated hospitalization through 150 days after dosing was generally comparable between ENFLONSIA (incidence rate=1.3%, 95% CI: 0.4, 2.9) and palivizumab (incidence rate=1.5%, 95% CI: 0.5, 3.2).