Drug Trials Snapshots: ENFLONSIA
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the ENFLONSIA Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
ENFLONSIA (clesrovimab)
En-flahn-see-ah
Merck Sharp & Dohme LLC
Approval date: June 9, 2025
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ENFLONSIA is a monoclonal antibody that 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.
How is this drug used?
ENFLONSIA is administered intramuscularly (IM) as a single 105 mg dose.
Who participated in the clinical trials?
The FDA approved ENFLONSIA based on evidence from two clinical trials (Trials 004 and 007) for the prevention of RSV lower respiratory tract disease in neonates and infants who are born during or entering their first RSV season.
Trial 004 was a 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 gestational age [GA]) and late preterm and full-term infants (≥35 weeks GA). Among 3,614 participants who received ENFLONSIA or saline placebo, the median age of infants was 3.1 months (range: 0 to 12 months); 80% were younger than 6 months, 16% were between 6 to 9 months, and 4% were 9 months of age and older; and 51% were male. Of these participants, 18% were GA between 29 weeks and 35 weeks, and 82% were GA 35 weeks and older. 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; and 28% were of Hispanic or Latino ethnicity. Among U.S. participants (N=478) who were randomized and received ENFLONSIA or saline placebo, the median age of infants was 3.2 months (range: 0 to 12 months); 78% were younger than 6 months, 16% were between 6 to 9 months, and 6% were 9 months of age and older; and 50% were male. Of these participants, 13% were GA between 29 weeks and 35 weeks, and 87% were GA 35 weeks and older. The racial distribution was as follows: 85% were White, 7% were multi-racial, 6% were Black or African American, and 2% were other races; and 17% were of Hispanic or Latino ethnicity.
Trial 007 was a 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 (CLD) of prematurity or congenital heart disease (CHD) of any GA, who are at increased risk for severe RSV disease. Among 896 participants who received ENFLONSIA or palivizumab, the median age of infants was 2.5 months (range: 0 to 12 months); 89% were younger than 6 months, 9% were between 6 to 9 months, and 2% were 9 months of age and older; and 50% were male. Of these participants, 28% had CLD, 11% had CHD, 6% were GA younger than 29 weeks with neither CLD nor CHD and 55% were GA 29 weeks and older 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; and 32% were of Hispanic or Latino ethnicity. Among U.S. participants (N=40) who were randomized and received ENFLONSIA or palivizumab, the median age of infants was 3.5 months (range: 0 to 9 months); 85% were younger than 6 months, 15% were between 6 to 9 months; and 53% were male. Of these participants, 38% were GA younger than 29 weeks, 55% were GA between 29 weeks and 35 weeks, and 7% were GA 35 weeks and older. The racial distribution was as follows: 68% were White, 23% were Black or African American, 7% were multi-racial, and 2% were other races; and 40% were of Hispanic or Latino ethnicity.
How were the trials designed?
The safety and efficacy of ENFLONSIA were supported by two clinical trials (Trials 004 and 007). The key measure of efficacy was the incidence of RSV-associated medically attended lower respiratory infection (MALRI) characterized as cough or difficulty breathing and requiring ≥1 indicator of lower respiratory infection (wheezing, rales/crackles) or severity (chest wall in-drawing/retractions, hypoxemia, tachypnea, dehydration due to respiratory symptoms) through 150 days after dosing. Medically attended includes all healthcare provider visits in settings such as outpatient clinic, clinical study site, emergency department, urgent care center, and/or hospital.
Trials 004 and 007 were randomized, multicenter clinical trials to evaluate the safety, pharmacokinetics (PK) and efficacy of ENFLONSIA in preventing RSV-associated MALRI. Trial 004 was a double-blind, placebo-controlled trial in which 3,614 infants (born at ≥29 to <35 weeks GA or at ≥35 weeks GA) were randomized and received at least one dose of either ENFLONSIA or placebo. Trial 007 was a partially-blind, palivizumab-controlled trial in which 896 infants who were at increased risk for severe RSV disease (born at ≥29 to ≤35 weeks GA or with chronic lung disease of prematurity or congenital heart disease of any GA) were randomized and received at least one dose of ENFLONSIA or palivizumab.
How were the trials designed?
Trial 004 was a Phase 2b/3, randomized, double-blind placebo-controlled, multi-site trial conducted 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.
Trial 007 was 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 1:1 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.
The key differences between Trials 004 and 007 were the study populations and study objectives. Specifically, Trial 004 was a Phase 2b/3 study in healthy infants ≥29 weeks GA, whereas Trial 007 was a Phase 3 study in infants at increased risk for severe RSV disease (i.e., 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). In Trial 004, the primary efficacy endpoint was the incidence of RSV-associated MALRI through Day 150. In Trial 007, safety was the primary endpoint, and the efficacy of ENFLONSIA in infants at increased risk for severe RSV disease, was established by extrapolation of efficacy of ENFLONSIA from Trial 004 to Trial 007 based on similar pharmacokinetic exposure.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes the number of participants, by sex, enrolled in the placebo-controlled clinical trial (Trial 004) used to evaluate the safety and efficacy of ENFLONSIA in early and moderate preterm infants (≥29 to <35 weeks GA) and late preterm and full-term infants (>e;35 weeks GA).
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of participants by race enrolled in Trial 004.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes the percentage of participants by age enrolled in Trial 004.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes the percentage of participants by ethnicity enrolled in Trial 004.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trial?
Table 1 summarizes the demographics of participants in Trials 004 and 007.
Table 1. Baseline Demographics of Participants by Treatment Group, Trials 004 and 007
| Demographic | Trial 004 |
Trial 007 |
||
|---|---|---|---|---|
ENFLONSIA |
Placebo |
ENFLONSIA |
Palivizumab |
|
| Sex | ||||
| Male | 1228 (50.9) |
617 (51.3) |
225 (50.4) |
221 (49.1) |
| Female | 1183 (49.1) |
586 (48.7) |
221 (49.6) |
229 (50.9) |
| Age group, months |
|
|
|
|
| <6 | 1918 (79.6) |
960 (79.8) |
409 (91.7) |
390 (86.7) |
| ≥6 to <9 | 388 (16.1) |
196 (16.3) |
33 (7.4) |
51 (11.3) |
| ≥9 | 105 (4.4) |
47 (3.9) |
4 (<1) |
9 (2.0) |
| Race |
|
|
|
|
| American Indian or Alaska Native | 50 (2.1) |
18 (1.5) |
5 (1.1) |
7 (1.6) |
| Asian | 641 (26.6) |
320 (26.6) |
82 (18.4) |
80 (17.8) |
| Black or African American | 326 (13.5) |
171 (14.2) |
67 (15.0) |
71 (15.8) |
| Multiple | 302 (12.5) |
138 (11.5) |
56 (12.6) |
53 (11.8) |
| Native Hawaiian or other Pacific Islander | 1 (<1) |
1 (<1) |
5 (1.1) |
2 (<1) |
| White | 1082 (44.9) |
550 (45.7) |
231 (51.8) |
237 (52.7) |
| Missing | 9 (<1) |
5 (<1) |
0 |
0 |
| Ethnicity |
|
|
|
|
| Hispanic or Latino | 682 (28.3) |
335 (27.8) |
138 (30.9) |
146 (32.4) |
| Not Hispanic or Latino | 1660 (68.9) |
834 (69.3) |
296 (66.4) |
296 (65.8) |
| Unknown or missing | 69 (2.9) |
34 (2.8) |
12 (2.7) |
8 (1.8) |
Source: Adapted from FDA Review
What are the benefits of this drug?
ENFLONSIA contains antibodies to help prevent RSV disease in neonates and infants who are born during or entering their first RSV season for up to five months.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2 summarizes efficacy results for the primary and key secondary efficacy endpoints in Trial 004, which were the incidence of RSV-associated MALRI and the incidence of RSV-associated hospitalization in infants born at 29 weeks or older GA Days 1 through 150 post-dose.
Table 2. Incidence of RSV-Associated Disease in Infants Born at ≥29 Weeks GA Days 1 Through 150 Post-Dose, Trial 004, Efficacy
| RSV‑Associated Endpoint | ENFLONSIA, N=2411 |
Placebo, N=1203 |
Efficacy1 (95% CI)2 |
||
|---|---|---|---|---|---|
n |
Incidence Rate>5 months |
n |
Incidence Rate |
||
| MALRI (requiring ≥1 indicator of LRI or severity) | 60 |
0.026 |
74 |
0.065 |
60.5% (44.2, 72.0)* |
| Hospitalization | 9 |
0.004 |
28 |
0.024 |
84.3% (66.7, 92.6)* |
Source: Adapted from ENFLONSIA Prescribing Information
* p<0.001 1 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. 2 Estimate and 95% CI of efficacy were estimated from the modified Poisson regression with robust variance method.
Abbreviations: CI, confidence interval; GA, gestational age; LRI, lower respiratory infection; MALRI, medically attended lower respiratory infection; n, number of cases; N, number of participants eligible for inclusion in the full analysis set population; RSV, respiratory syncytial virus
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: ENFLONSIA worked better in females than in males. Because of limited data, this difference may be due to chance.
- Race: ENFLONSIA worked similarly in White, Asian, and Black or African American participants.
- Age: ENFLONSIA worked better in younger infants who were younger than 6 months old compared to those older than or equal to 6 months old. Because of limited data, this difference may be due to chance.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3 summarizes the primary efficacy endpoint, the incidence of RSV-associated disease Days 1 through 150 post-dose by demographic subgroups of infants in Trial 004.
Table 3. Efficacy Results by Sex, Race, Age, and Ethnicity, Trial 004, Efficacy Population
| Demographic | ENFLONSIA, N=2411 |
Placebo, N=1203 |
Efficacy2 (95% CI)3 |
||
|---|---|---|---|---|---|
n/Ns |
Incidence Rate |
n/Ns |
Incidence Rate |
||
| Sex |
|
|
|
|
|
| Male | 42/1228 |
0.035 |
42/617 |
0.072 |
51.0 (24.5, 68.2) |
| Female | 18/1183 |
0.016 |
32/586 |
0.057 |
72.8 (51.4, 84.8) |
| Age, months |
|
|
|
|
|
| <6 | 47/1918 |
0.025 |
66/960 |
0.073 |
65.5 (49.7, 76.5) |
| ≥6 to <9 | 10/388 |
0.027 |
6/196 |
0.032 |
15.6 (-139.2, 70.5) |
| ≤9 | 3/105 |
0.029 |
2/47 |
0.044 |
32.9 (-440.8, 89.6) |
| Race |
|
|
|
|
|
| American Indian or Alaska Native | 0/50 |
0 |
0/18 |
0 |
NA |
| Asian | 9/641 |
0.014 |
12/320 |
0.038 |
62.8 (11.5, 84.4) |
| Black or African American | 9/326 |
0.029 |
13/171 |
0.083 |
64.9 (17.3, 85.1) |
| Multiple | 18/302 |
0.063 |
12/138 |
0.094 |
32.5 (-42.1, 67.9) |
| Native Hawaiian or other Pacific Islander | 0/1 |
0 |
0/1 |
0 |
NA |
| White | 24/1082 |
0.023 |
37/550 |
0.071 |
68.2 (46.6, 81.0) |
Source: Adapted from FDA Review
1 Five months is defined as 150 days. 2 Efficacy for MALRI (requiring ≥1 indicator of LRI or severity) based on relative risk reduction against placebo. 3 For the subgroup efficacy analyses, the efficacy and 95% CI were estimated from the Poisson regression model with robust variance method, or an exact binomial method if convergence issues exist with the Poisson approach.
Abbreviations: CI, confidence interval; LRI, lower respiratory infection; MALRI, medically attended lower respiratory infection; N, number of patients in treatment arm; n, number of cases; NA, not applicable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
What are the possible side effects?
The most common side effects observed during the clinical trials of ENFLONSIA were redness and swelling at the site of the ENFLONSIA injection and rash.
Serious allergic reactions have occurred with medicines like ENFLONSIA, including any of the following:
- swelling of face, mouth, or tongue
- difficulty swallowing or breathing
- muscle weakness
- severe rash, hives, or itching
- bluesish color of skin, lips, or under fingernails
- unresponsiveness
title="MORE INFO" open="no"
What are the possible side effects (results of trials used to assess safety)?
The safety of ENFLONSIA was supported by two clinical trials: one trial in neonates and infants who were otherwise healthy and were born between 29 to 35 weeks GA or at 35 weeks and older GA (Trial 004); and in a trial of infants and children who were at increased risk of severe RSV disease (Trial 007). A total of 2,858 infants received ENFLONSIA and were assessed for safety.
The most common adverse reactions in Trial 004 in the ENFLONSIA group and occurring at a higher frequency than in the placebo group were redness at the injection site (3.7% and 3.3%, respectively), swelling at the injection site (2.7% and 2.6%, respectively) and rash (2.3% and 1.9%, respectively). Most (≥97%) of the adverse reactions were mild or moderate in severity.
The safety profile of ENFLONSIA in infants at increased risk of severe RSV disease entering their first season (Trial 007) was similar to palivizumab and consistent with the safety profile of ENFLONSIA in healthy infants (Trial 004).
Were there any differences in side effects among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The occurrence of side effects was similar in White, Asian, and Black or African American participants.
- Age: The safety of ENFLONSIA was assessed in infants and children ≤12 months of age and was not assessed in children older than 12 months of age. Side effects were generally similar regardless of age. However, most of the participants were younger than 6 months of age and data were limited for older age groups.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 4 and Table 5 show analyses of side effects by subgroups of sex, race, and age in Trials 004 and 007.
Table 4. Subgroup Analysis of Side Effects by Sex, Race, Age, and Ethnicity, Trial 004, Safety Population
| Characteristic | ENFLONSIA |
Placebo |
Risk Difference |
|---|---|---|---|
| Sex |
|
|
|
| Female | 865/1180 (73.3) |
442/586 (75.4) |
‑2.1 (‑6.3, 2.3) |
| Male | 951/1229 (77.4) |
476/616 (77.3) |
0.1 (‑3.9, 4.2) |
| Age group, months |
|
|
|
| <6 | 1412/1921 (73.5) |
730/963 (75.8) |
‑2.3 (‑5.6, 1.1) |
| ≤6 to <9 | 313/383 (81.7) |
152/192 (79.2) |
2.6 (‑4.1, 9.8) |
| ≤9 | 91/105 (86.7) |
36/47 (76.6) |
10.1 (‑2.5, 25.1) |
| Race |
|
|
|
| American Indian or Alaska Native | 34/50 (68.0) |
11/18 (61.1) |
6.9 (‑17.0, 32.9) |
| Asian | 447/638 (70.1) |
227/320 (70.9) |
‑0.9 (‑6.9, 5.4) |
| Black or African American | 239/327 (73.1) |
115/170 (67.6) |
5.4 (‑2.9, 14.1) |
| Multiple | 242/302 (80.1) |
103/138 (74.6) |
5.5 (‑2.7, 14.4) |
| Native Hawaiian or other Pacific Islander | 1/1 (100) |
1/1 (100) |
0.0 (‑88.5, 88.5) |
| White | 845/1082 (78.1) |
456/550 (82.9) |
‑4.8 (‑8.7, ‑0.7) * |
| Missing | 8/9 (88.9) |
5/5 (100) |
-11.1 (‑44.8, 36.6) |
| Ethnicity |
|
|
|
| Hispanic or Latino | 474/682 (69.5) |
238/335 (71.0) |
‑1.5 (‑7.4, 4.5) |
| Not Hispanic or Latino | 1290/1658 (77.8) |
657/833 (78.9) |
‑1.1 (‑4.4, 2.4) |
| Not reported | 14/17 (82.4) |
8/10 (80.0) |
2.4 (‑27.1, 37.4) |
| Unknown | 36/49 (73.5) |
14/23 (60.9) |
12.6 (‑9.7, 36.0) |
| Missing | 2/3 (66.7) |
1/1 (100) |
-33.3 (‑82.7, 66.9) |
| Is in United States |
|
|
|
| United States | 267/322 (82.9) |
137/156 (87.8) |
‑4.9 (‑11.2, 2.2) |
| Non-United States | 1549/2087 (74.2) |
781/1046 (74.7) |
‑0.4 (‑3.6, 2.8) |
Source: Adapted from FDA Review
Risk difference (with 95% confidence interval) is shown between total treatment and comparator.
Asterisk (*) indicates that 95% confidence interval excludes zero.
Abbreviations: CI, confidence interval; N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
Table 5. Subgroup Analysis of Side Effects by Sex, Race, Age, and Ethnicity, Trial 007, Safety Population
| Characteristic | ENFLONSIA |
Palivizumab |
Risk Difference |
|---|---|---|---|
| Sex |
|
|
|
| Female | 161/221 (72.9) |
145/229 (63.3) |
9.5 (0.9, 18.0) * |
| Male | 152/224 (67.9) |
154/221 (69.7) |
‑1.8 (‑10.4, 6.8) |
| Age group, months |
|
|
|
| <6 | 282/408 (69.1) |
253/390 (64.9) |
4.2 (‑2.3, 10.8) |
| ≤6 to <9 | 28/33 (84.8) |
41/51 (80.4) |
4.5 (‑13.8, 20.5) |
| ≤9 | 3/4 (75.0) |
5/9 (55.6) |
19.4 (‑37.8, 61.0) |
| Race |
|
|
|
| American Indian or Alaska Native | 2/5 (40.0) |
3/7 (42.9) |
‑2.9 (‑52.3, 49.4) |
| Asian | 53/82 (64.6) |
50/80 (62.5) |
2.1 (‑12.6, 16.8) |
| Black or African American | 58/67 (86.6) |
56/71 (78.9) |
7.7 (‑5.2, 20.5) |
| White | 161/231 (69.7) |
155/237 (65.4) |
4.3 (‑4.2, 12.7) |
| Native Hawaiian or other Pacific Islander | 5/5 (100) |
1/2 (50.0) |
50.0 (‑15.0, 91.6)/td> |
| Multiple | 34/55 (61.8) |
34/53 (64.2) |
‑2.3 (‑20.3, 15.8) |
| Ethnicity |
|
|
|
| Hispanic or Latino | 91/137 (66.4) |
97/146 (66.4) |
‑0.0 (‑11.0, 10.9) |
| Not Hispanic or Latino | 212/296 (71.6) |
195/296 (65.9) |
5.7 (‑1.7, 13.2) |
| Not reported | 5/7 (71.4) |
4/5 (80.0) |
‑8.6 (‑53.3, 44.1) |
| Unknown | 5/5 (100) |
3/3 (100) |
0.0 (‑46.8, 59.4) |
| Is in United States |
|
|
|
| United States | 12/16 (75.0) |
19/24 (79.2) |
‑4.2 (‑32.6, 21.7) |
| Non-United States | 301/429 (70.2) |
280/426 (65.7) |
4.4 (‑1.8, 10.7) |
Source: Adapted from FDA Review
Risk difference (with 95% confidence interval) is shown between total treatment and comparator.
Asterisk (*) indicates that 95% confidence interval excludes zero.
Abbreviations: CI, confidence interval; N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.
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