Drug Trials Snapshots: BEYFORTUS
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 BEYFORTUS 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).
BEYFORTUS (nirsevimab)
Bay for’ tus
Astra Zeneca AB
Original Approval date: July 17, 2023
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
BEYFORTUS is indicated for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in:
- Neonates and infants born during or entering their first RSV season
- Children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season
How is this drug used?
BEYFORTUS is a monoclonal antibody with anti-RSV activity used to prevent RSV lower respiratory tract disease in neonates, infants, and certain children.
BEYFORTUS is administered intramuscularly (IM) once to neonates or infants born during or entering their first RSV season. In the first RSV season, the BEYFORTUS dosage is 50 mg IM in neonates and infants weighing <5 kg, and 100 mg IM in neonates and infants weighing ≥5 kg.
For children up to 24 months of age who remain vulnerable to severe RSV disease, a single 200 mg IM dose of BEYFORTUS is administered before their second RSV season.
Who participated in the clinical trials?
The FDA approved BEYFORTUS based on evidence from three clinical trials for the prevention of medically attended RSV lower respiratory tract disease. Trials 03 and 04 were randomized, double-blind, placebo-controlled, multicenter clinical trials to evaluate the safety, pharmacokinetics (PK) and efficacy of BEYFORTUS for the prevention of medically attended RSV lower respiratory tract infection (MA RSV LRTI). Trial 05 was a randomized, double-blind, active (palivizumab)-controlled, multicenter trial to evaluate the safety and PK of BEYFORTUS.
The trials were conducted at 421 sites in 33 countries from North America, Europe, Asia, South America, Australia, New Zealand, and South Africa. A total of 589 subjects who received BEYFORTUS were enrolled at U.S. sites and 1,988 were enrolled at non-U.S. sites.
The pooled safety population of subjects who received the recommended dose included Trial 03, which enrolled infants born at ≥29 to <35 weeks gestational age (GA), and Trial 04 (infants born at ≥35 weeks GA). In this pooled safety population, 52% percent of infants were male and 48% were female; 57% were White; 15% were Black; 4% were American Indian or Alaskan native; 4% were Asian; 1% were Pacific Islander; and 19% were other or mixed race; 30% were Hispanic or Latino. Twenty-two percent of infants were born at <35 weeks GA, 10% of infants were GA ≥35 weeks and <37 weeks; 68% were GA ≥37 weeks. The median chronological age was 2 months; 65% were ≤3 months; 28% were >3 to ≤6 months, and 7% were >6 months of age.
In Trial 05, which evaluated infants who were at a higher risk for severe RSV (born at GA <35 weeks or had chronic lung disease (CLD) of prematurity or hemodynamically significant congenital heart disease (CHD)), 54% were male; 79% were White; 10% were Black; 5% were Asian; 2% were American Indian or Alaskan Native; 15% were Hispanic or Latino. The median age was 3.5 months (range: 2 days to 12.3 months); 45% were ≤3 months; 34% were >3 to ≤6 months, and 21% were >6 months of age.
The number of subjects in the efficacy and safety populations differ because of different pooling of subjects analyzed for efficacy and safety.
How were the trials designed?
The safety and efficacy of BEYFORTUS were supported by three clinical trials (Trials 03, 04, and 05). The key measure of efficacy was the incidence of MA RSV LRTI, evaluated during the 150 days after BEYFORTUS administration. MA RSV LRTI included all health care provider visits for lower respiratory tract disease and a positive RSV test. Trials 03 and 04 were randomized, double-blind, and placebo-controlled, designed to assess the safety, PK, and efficacy of BEYFORTUS in preventing MA RSV LRTI. In total, 2,943 infants were enrolled in Trials 03 and 04. Trial 05, a randomized, double-blind, active (palivizumab)-controlled trial, evaluated BEYFORTUS in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. The trial enrolled 925 preterm infants and infants with CLD of prematurity or CHD. The safety and PK data from Trial 05 provided evidence for the use of BEYFORTUS to prevent MA RSV LRTI in this population.
How were the trials designed?
Trials 03 and 04 were double-blind efficacy trials, where subjects were randomized in a 2:1 ratio to receive BEYFORTUS (N=1963) or placebo (N=980) and followed for one RSV season to assess efficacy. The primary efficacy endpoint for both trials was the incidence of MA RSV LRTI (hospitalized or non-hospitalized) by Day 150 postdose. All efficacy objectives and endpoints were the same across both studies.
The key differences between Trials 03 and 04 were the study populations and dose selections. Specifically, Trial 03 was a Phase 2b study in very and moderately preterm infants (i.e., born at ≥29 to <35 weeks of gestation). All subjects randomized to the BEYFORTUS treatment arm received a 50 mg IM dose regardless of baseline body weight.
Trial 04 was a Phase 3 study in term and late preterm infants (i.e., born at ≥35 weeks of gestation). The dose selection for subjects randomized to the BEYFORTUS treatment arm was based on baseline body weight: subjects weighing <5 kg received a single 50 mg IM dose, while subjects weighing ≥5 kg received a single 100 mg dose of BEYFORTUS.
Trial 05 was a Phase 2/3 randomized, double-blind, palivizumab-controlled, multicenter trial in pediatric subjects born at <35 weeks GA and infants with CLD of prematurity or hemodynamically significant CHD. In the first RSV season of the trial, subjects were randomized 2:1 to receive BEYFORTUS (N=614) or palivizumab (N=304) by IM injection. Pediatric subjects with CLD of prematurity or hemodynamically significant CHD up to 24 months of age continued in the trial for a second RSV season (N=262). Subjects who received BEYFORTUS during their first RSV season also received a single dose of BEYFORTUS entering their second RSV season (N=180). Subjects who received palivizumab during their first RSV season were re-randomized 1:1 to either receive BEYFORTUS or palivizumab entering their second RSV season.
The primary endpoint was safety, and study subjects were followed for 360 days after receiving BEYFORTUS in each RSV season. This trial was not designed to demonstrate efficacy, but efficacy was assessed as secondary endpoint.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes the number of subjects, by sex, enrolled in the active-controlled clinical trial (Trial 05) used to evaluate the safety and PK of BEYFORTUS in infants at high risk of developing RSV LRTI.
Figure 1. Baseline Demographics by Sex
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of subjects by race enrolled in Trial 05.
Figure 2. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 3 summarizes the percentage of subjects by age enrolled in Trial 05.
Figure 3. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 4 summarizes the percentage of subjects by ethnicity enrolled in Trial 05.
Figure 4. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Who participated in the trials?
Table 1 summarizes the demographics of subjects in the Trials 03 and 04.
Table 1. Demographics by Treatment Group, Trials 03 and 04
|
Demographic |
Trial 03 |
Trial 04 |
||
|---|---|---|---|---|
|
BEYFORTUS |
Placebo |
BEYFORTUS |
Placebo |
|
|
Sex |
||||
|
Female |
468 (48.3) |
224 (46.3) |
464 (46.7) |
257 (51.8) |
|
Male |
501 (51.7) |
260 (53.7) |
530 (53.3) |
239 (48.2) |
|
Age group, months |
||||
|
≤3.0 |
516 (53.3) |
257 (53.1) |
577 (58.0) |
285 (57.5) |
|
>3.0 to ≤6.0 |
320 (33.0) |
153 (31.6) |
317 (31.9) |
162 (32.7) |
|
>6.0 |
133 (13.7) |
74 (15.3) |
100 (10.1) |
49 (9.9) |
|
Race |
||||
|
American Indian or Alaska Native |
0 |
1 (<1) |
57 (5.7) |
26 (5.2) |
|
Asian |
5 (<1) |
10 (2.1) |
36 (3.6) |
18 (3.6) |
|
Black or African American |
189 (19.5) |
67 (13.8) |
286 (28.8) |
136 (27.4) |
|
Multiple |
12 (1.2) |
5 (1.0) |
12 (1.2) |
1 (<1) |
|
Native Hawaiian or other Pacific Islander |
8 (<1) |
3 (<1) |
6 (<1) |
5 (1.0) |
|
Other |
61 (6.3) |
43 (8.9) |
70 (7.0) |
38 (7.7) |
|
White |
693 (71.5) |
355 (73.3) |
524 (52.7) |
272 (54.8) |
|
Not reported |
1 (<1) |
0 |
3 (<1) |
0 |
|
Ethnicity |
||||
|
Hispanic or Latino |
225 (23.2) |
91 (18.8) |
100 (10.1) |
51 (10.3) |
|
Not Hispanic or Latino |
743 (76.7) |
393 (81.2) |
890 (89.5) |
443 (89.3) |
|
Not reported |
1 (<1) |
0 |
4 (<1) |
2 (<1) |
Source: Adapted from FDA Review
Table 2 summarizes demographics of subjects in the Trial 05.
Table 2. Demographics by Treatment Group, Trial 05
|
Characteristic |
BEYFORTUS |
PALIVISUMAB |
|---|---|---|
|
Sex |
||
|
Female |
296 (48.2) |
131 (43.1) |
|
Male |
318 (51.8) |
173 (56.9) |
|
Age group, months |
||
|
≤3.0 |
273 (44.5) |
140 (46.1) |
|
>3.0 to ≤6.0 |
209 (34.0) |
101 (33.2) |
|
>6.0 |
132 (21.5) |
63 (20.7) |
|
Race |
||
|
American Indian or Alaska Native |
11 (1.8) |
5 (1.6) |
|
Asian |
36 (5.9) |
14 (4.6) |
|
Black or African American |
59 (9.6) |
29 (9.5) |
|
Multiple |
6 (1.0) |
4 (1.3) |
|
Native Hawaiian or other Pacific Islander |
4 (0.7) |
1 (0.3) |
|
Other |
17 (2.8) |
6 (2.0) |
|
White |
481 (78.3) |
244 (80.3) |
|
Missing |
0 |
1 (0.3) |
|
Ethnicity |
||
|
Hispanic or Latino |
99 (16.1) |
41 (13.5) |
|
Not Hispanic or Latino |
515 (83.9) |
262 (86.2) |
|
Missing |
0 |
1 (0.3) |
Source: Adapted from FDA Review
What are the benefits of this drug?
BEYFORTUS is an antibody that contains nirsevimab-alip which is used to help prevent RSV disease for up to five months
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 3 summarizes the results for the primary efficacy endpoint in Trials 03 and 04, which was the incidence of MA RSV LRTI by Day 150 postdose in neonates and infants entering their first RSV season, comparing BEYFORTUS with placebo in infants.
Table 3. Incidence of Medically Attended RSV Lower Respiratory Tract Infection by Day 150 Postdose
|
Endpoint |
Trial 3 |
Trial 4 |
||
|---|---|---|---|---|
|
BEYFORTUS |
Placebo |
BEYFORTUS |
Placebo |
|
|
Incidence of MA RSV LTRI through 150 days postdose |
25 (2.6) |
46 (9.5) |
12 (1.2) |
25 (5.0) |
|
Efficacya, % (95% CI) |
70.1 (52.3, 81.2)b |
74.9 (50.6, 87.3) |
||
Source: Adapted from BEYFORTUS Prescribing Information
a Efficacy for MA RSV LRTI based on relative risk reduction against placebo adjusted for age at randomization and hemisphere.
b In all randomized subjects in Trial 03 weighing <5kg at baseline, and who received the recommended dose of BEYFORTUS, efficacy for MA RSV LRTI, based on relative risk reduction against placebo was 86.2% (68.0, 94.0)
Abbreviations: CI, confidence interval; LRTI, lower respiratory tract infection; MA, medically attended; RSV, respiratory syncytial virus
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: BEYFORTUS worked similarly in male and female infants.
- Race: BEYFORTUS worked similarly in White and Black or African American infants.
- Age: BEYFORTUS was studied in infants and children younger than 24 months of age. BEYFORTUS worked similarly in infants who were 3 months of age or younger, in those who were 3 to 6 months of age, and in those who were older than 6 months of age. The numbers of infants older than 6 months of age were small in these trials. Efficacy was not assessed in adults, including those older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 4 and Table 5 summarizes the primary efficacy endpoint, the incidence of MA RSV LRTI by Day 150 postdose, by demographic subgroups of infants in Trials 03 and 04.
Table 4. Subgroup Analysis: Incidence of Medically Attended RSV Lower Respiratory Tract Infection by Day 150 Postdose, Trial 03
|
|
BEYFORTUS |
Placebo |
RRR |
|---|---|---|---|
|
Sex |
|||
|
Female |
9/468 (1.9) |
24/224 (10.7) |
79.95 (57.8, 90.5) |
|
Male |
16/501 (3.2) |
22/260 (8.5) |
60.69 (26.4, 79.0) |
|
Race |
|||
|
White |
21/693 (3.0) |
38/355 (10.7) |
69.9 (50.0, 81.8) |
|
Black or African American |
3/189 (1.6) |
5/67 (7.5) |
79.1 (25.6, 94.1) |
|
Others |
1/87 (1.2) |
3/62 (4.8) |
74.0 (-93.6, 96.5) |
|
Age, months |
|||
|
≤3 |
7/516 (1.4) |
22/257 (8.6) |
82.7 (60.4, 92.5) |
|
>3 to ≤6 |
13/320 (4.1) |
16/153 (10.5) |
59.5 (18.3, 79.9) |
|
>6 |
5/133 (3.8) |
8/74 (8.1) |
62.4 (-8.8, 87) |
Source: Adapted from FDA Review
The model did not include the region term because of issues of non-convergence and because the number of events was small.
Abbreviations: CI, confidence interval; RSV, respiratory syncytial virus; RRR, relative risk reduction
Table 5. Subgroup Analysis: Incidence of Medically Attended RSV Lower Respiratory Tract Infection by Day 150 Postdose, Trial 04
|
|
BEYFORTUS |
Placebo |
RRR |
|---|---|---|---|
|
Sex |
|||
|
Female |
5/462 (1.1) |
13/253 (5.1) |
79.1 (42.4, 92.4) |
|
Male |
7/516 (1.3) |
12/236 (5.1) |
71.6 (27.9, 88.8) |
|
Race |
|||
|
White |
8/516 (1.6) |
17/266 (6.4) |
74.1 (40.8, 88.7) |
|
Black or African American |
0/286 (0.0) |
2/136 (1.5) |
NA* |
|
Others |
4/184 (2.2) |
6/88 (6.8) |
68.8 (-11.6, 91.3) |
|
Age, months |
|||
|
≤3 |
10/567 (1.8) |
12/280 (4.3) |
57.2 (2.2, 81.2) |
|
>3 to ≤6 |
2/313 (0.6) |
10/160 (6.3) |
89.2 (51.3, 97.6) |
|
>6 |
0/98 (0.0) |
3/49 (6.1) |
NA* |
Source: Adapted from FDA Review
* RRR cannot be calculated because the number of events was not sufficient.
Abbreviations: CI, confidence interval; NA, not applicable; RSV, respiratory syncytial virus; RRR, relative risk reduction
What are the possible side effects?
The most common side effects observed during the clinical trials of BEYFORTUS were rash, and pain, swelling, or hardness at the site of the BEYFORTUS injection.
Serious allergic reactions have happened with medicines like BEYFORTUS, 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
What are the possible side effects (results of trials used to assess safety)?
The safety of BEYFORTUS was supported by three clinical trials: two trials in neonates and infants (Trials 03 and 04), who were otherwise healthy, and who were born at ≥29 weeks GA, and in a trial in infants and children (Trial 05) who were at high risk of severe RSV disease. A total of 3,224 infants received the recommended dose of BEYFORTUS and were assessed for safety.
The most common adverse reactions in Trials 03 and 04 in the BEYFORTUS group and occurring at a greater frequency than in the placebo group were reactions at the BEYFORTUS injection site (0.3% and 0%, respectively) and rash within two weeks of receiving BEYFORTYS (0.9% and 0.6%, respectively). Adverse reactions reported in Trial 05 were similar to those reported in Trials 03 and 04.
Were there any differences in side effects of the clinical trials among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The occurrence of side effects was lower in White subjects than in other racial and ethnic subgroups. However, the number of subjects in some racial subgroups was too small to draw definitive conclusions about racial differences in side effects.
- Age: BEYFORTUS was studied in infants and children younger than 24 months of age and was not studied in children older than 2 years of age. Side effects were similar regardless of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 6, Table 7, and Table 8 show side effects by subgroups of sex, race, and age in Trials 03, 04, and 05.
Table 6. Subgroup Analysis of Side Effects by Sex – Pooled Trial 03, Trial 04, and Trial 05
|
Sex |
Pooled Trials 03 and 04 |
Trial 05 |
||
|---|---|---|---|---|
|
BEYFORTUS |
Placebo |
BEYFORTUS |
Palivizumab |
|
|
Male |
1151/1362 (84.5) |
541/647 (83.6) |
212/296 (71.6) |
92/131 (70.2) |
|
Female |
1007/1208 (83.4) |
519/637 (81.5) |
232/318 (73.0) |
123/173 (71.1) |
Source: Adapted from FDA Review
Abbreviations: N, number of patients in treatment arm; n, number of patients meeting criteria; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
Table 7. Subgroup Analysis of Side Effects by Race – Pooled Trial 03, Trial 04, and Trial 05
|
Race |
Pooled Trials 03 and 04 |
Trial 05 |
||
|---|---|---|---|---|
|
BEYFORTUS |
Placebo |
BEYFORTUS |
Palivizumab |
|
|
American Indian or Alaska Native |
87/92 (94.6) |
43/52 (82.7) |
7/11 (63.6) |
4/5 (80.0) |
|
Black or African American |
387/416 (93.0) |
166/178 (93.3) |
55/59 (93.2) |
26/29 (89.7) |
|
Multiple |
21/25 (84.0) |
9/11 (81.8) |
5/6 (83.3) |
4/4 (100) |
|
White |
1097/1441 (76.1) |
564/740 (76.2) |
325/481 (67.6) |
162/244 (66.4) |
|
Asian |
98/111 (88.3) |
44/56 (78.6) |
33/36 (91.7) |
11/14 (78.6) |
|
Native Hawaiian or other Pacific Islander |
20/21 (95.2) |
8/11 (72.7) |
4/4 (100) |
1/1 (100) |
|
Other |
444/460 (96.5) |
226/236 (95.8) |
15/17 (88.2) |
6/6 (100) |
|
Missing |
4/4 (100) |
0/0 (NA) |
0/0 (NA) |
1/1 (100) |
Source: Adapted from FDA Review
Abbreviations: N, number of patients in treatment arm; n, number of patients meeting criteria; NA, not applicable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
Table 8. Subgroup Analysis of Side Effects by Age – Pooled Trial 03, Trial 04, and Trial 05
|
Age, months |
Pooled Trials 03 and 04 |
Trial 05 |
||
|---|---|---|---|---|
|
BEYFORTUS |
Placebo |
BEYFORTUS |
Palivizumab |
|
|
≤3 |
1404/1675 (83.8) |
688/828 (83.1) |
185/273 (67.8) |
103/140 (73.6) |
|
>3 to ≤6 |
616/716 (86.0) |
300/362 (82.9) |
162/209 (77.5) |
71/101 (70.3) |
|
>6 |
138/179 (77.1) |
72/94 (76.6) |
97/132 (73.5) |
41/63 (65.1) |
Source: Adapted from FDA Review
Abbreviations: N, number of patients in treatment arm; n, number of patients meeting criteria; 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 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.