Evaluation of pharmacokinetics and safety profile of Nirsevimab before initiating a clinical study in infants
Evaluation of pharmacokinetics and safety profile of Nirsevimab in healthy preterm infants
Pivotal clinical trials
2016
Phase 2b3 NCT02878330
“Infants not eligible to receive Palivizumab as per AAP / other guidelines”
Evaluation of nirsevimab for the prevention of RSV-associated lower respiratory tract infection in healthy infants
Healthy preterm infants in healthy infants 29-34 weeks 6 days wGA (n=1453)
2019
Phase 34,5 NCT03979313
Evaluation of efficacy and safety of nirsevimab in healthy late-preterm and term infants entering their first RSV season
Healthy late preterm and term infants ≥ 35 wGA (n=3012)
Due to COVID-19, no RSV cases were observed. Therefore, a joint decision with health authorities was taken to analyze the primary endpoint (primary cohort). MELODY trial restarted to further characterize nirsevimab safety in this population (secondary cohort)
2019
Phase 2/36-8 NCT03959488
‘MEDLEY’
Evaluation of safety of nirsevimab in preterm infants with OR without CHD or CLD of prematurity
Preterm cohort (n=615)
2019
CHD/CLD cohort (n=310)
Season 2† (n=262)
2020
Phase 29,31 NCT04484935
‘MUSIC’
Evaluation of safety and tolerability, for nirsevimab in immunocompromised children
Immunocompromised children who are ≤ 24 months of age at the time of dose administration. (n=100)
2022
Phase 3b10 NCT05437510
‘HARMONIE’
Determination of efficacy and safety of nirsevimab for the prevention of hospitalizations due to RSV-LRTI in all palivizumab ineligible infants under 12 months
Healthy infants ≥29 wGA not eligible for palivizumab (n=8058)
Key results from the clinical development program of nirsevimabs
Safety
Nirsevimab (N=3580): Favorable Safety Profile Across All Infants in pivotal studies
Ph2b3 29-<35 wGA
MELODY4 ≥35 wGA
MEDLEY First season6
Preterm
CHD/CLD
Variables
Placebo (N=479)
Nirsevimab (N=968)
Placebo (N=996)
Nirsevimab (N=1998)
Palivizumab (N=206)
Nirsevimab (N=406)
Palivizumab (N=98)
Nirsevimab (N=208)
Serious adverse events
16.9%
11.2%
7.4%
6.3%
5.3%
6.9%
20.4%
19.2%
Adverse events of Grade 3 or higher
12.5%
8.0%
3.8%
3.1%
3.4
3.4%
13.3%
14.4%
Adverse events of special interest (AESI)
0.6%
0.5%
0.0%
0.2%
0.0%
0.2%
0.0%
0.5%
Deaths
3
2
0
4
0
2
1
3
None of the serious adverse events or deaths were considered as related to nirsevimab
Overall, incidence of nirsevimab antidrug antibody was low across studies with no safety concerns
MELODY: Four AESI cases of hypersensitivity limited to cutaneous signs and symptoms
MEDLEY: 2 AESIs (nirsevimab arm): Maculopapular rash (preterm cohort) 92 days post nirsevimab dose and heparin-induced thrombocytopenia (CHD/CLD cohort) unrelated to treatment
Clinical experience of nirsevimab continues with HARMONIE, MUSIC, and MELODY
HARMONIE10,11
MUSIC9
MEDLEY Second season12
CHD/CLD
Variables
No intervention (N=4020)
Nirsevimab (N=4016)
Nirsevimab (N=100)
P/P (N=42)
P/N (N=40)
N/N (N=180)
Serious adverse events
1.7%
2.2%
30%
0%
10%
9.4%
Adverse events of Grade 3 or higher
1.1%
1.2%
31.7
31.7
10%
7.8%
Adverse events of special interest (AESI)
<0.1
<0.1
6.7%
6.7%
0.0%
0%
Deaths
0
0
1
1
0
0
Overall incidence of adverse events (AEs)13,14
Serious AEs and treatment-related AEs were balanced between Nirsevimab and placebo groups
No anaphylaxis or other serious allergic reactions
No thrombocytopenia attributed to study drug
No immune complex disease
Nonserious cutaneous hypersensibility reactions occurred in 0.2% of nirsevimab recipients
Levels of ADA were low
Incidence of deaths were low and similar between groups
None were considered treatment-related
Key results from the clinical development program
Phase 1a1
Nirsevimab administration resulted in a 4X increase in neutralizing antibodies persisting until day 181 (ranging from 50% in 100 mg IM cohort to 83% in 3000 mg IV cohort)
Phase 1b/2a2
The extended half-life and the demonstrated RSV-neutralizing activity supported the potential for protection against RSV disease for the duration of a typical 5-month season with a single 50 mg IM dose of nirsevimab
Consistent efficacy against RSV-LRTI and associated hospitalizations
RSV MA-LRTI
RSV LRTI Hospitalization
RSV Very severe MA-LRTI
All Cause LRTI Hospitalization
All Cause MA-LRTI
Phase 2b3,15
(95% CI, 52.3-81.2)
(95% CI, 51.9-90.3)
(95% CI, 62.9, 95.8)
(95% CI, 16.3-60.5)
(95% CI, 7.1-37.0)
(95% CI, 62.3–85.2)
(95% CI, 49.4–89.4)
(95% CI, 48.8–91.0)
(95% CI, 6.3-60.2)
(95% CI, 23.7-50.0)
Phase 2b +(Pooled)5
(95% CI, 68.5-86.1)
(95% CI, 62.3-90.1)
(95% CI, 68.1-94.0)
(95% CI, 67.7-92.0)
(95% CI, 32.8-92.9)
(95% CI, 39.7-71.2)
All infants need protection from RSV16-21.
Nirsevimab is designed to provide protection for all infants for the length of typical RSV season with a single dose3,22.
Nirsevimab has demonstrated an efficacy of 79% against RSV-MA-LRTI (MELODY/Ph2b pooled), and 83% against hospitalizations (HARMONIE), for 150 days5,10.
Nirsevimab is the first-in-class and only prevention strategy approved by FDA and EMA and is designed to protect all infants from RSV-LRTI in their first RSV season23-25.
Regulatory approvals
NITAGs Recommend Nirsevimab for All Infants
Advisory Committee on Immunization Practices28
First RSV Season: All infants below 8 months of age
Second RSV Season: Infants and children (8-19 months) at increased risk of severe RSV
Haute Autorité de santé29
First RSV Season: All infants with reimbursements
inisterio de Sanidad30
First RSV Season: All infants below 6 months of age
Second RSV Season: High risk under 24 months
AAP: American Academy of Paediatrics; AESI: adverse event of special interest; CHD: Chronic Heart Disease; CLD: Chronic Ling Disease; FDA: Food and Drug Administration; EMA: European Medicines Agency; IM: Intramuscular; IV: Intravenous; LRTI: lower respiratory tract infection; RSV: respiratory syncytial virus; wGA: weeks of gestational age.
Domachowske J, et al. N Engl J Med. 2022;386(9):892-894.
NCT03959488. Accessed October 2023.
Domachowske JB. et al. ReSViNET’s 7th Conference (RSVVW 2023), 22- 24 February 2023.
Mori et al. Asian Congress of Pediatric Infectious Diseases, 26-28 October 2022, Seoul, Korea.
SB Drysdale, A Phase 3 randomized open-label study of nirsevimab (versus no intervention) in preventing hospitalizations due to respiratory syncytial virus (RSV) in infants (HARMONIE). ESPID 2023: Lisbon, Portugal.
SN Faust, (2023, Oct 10-15th). The Impact of Nirsevimab on an RSV Season in All Infants: Data From The HARMONIE Study [Oral presentation]. ID Week 2023 Boston, MA, USA
Domachowske JB, et al. J Pediatric Infect Dis Soc. 2023;12(8):477-480.
Beyfortus. Summary of Product Characteristics. November 2022.
Mankad V. Comprehensive summary of all safety data of nirsevimab in healthy infants: experience to date from pivotal trials. ESPID 2023 (May 8–12, 2023); Lisbon, Portugal.
Muller WJ. Safety and efficacy of nirsevimab for prevention of medically attended RSV lower respiratory tract infection in all infants enrolled in the phase 3 melody trial [Oral presentation]. RSVVW 2023: Lisbon, Portugal. (February 22–24, 2023) : Lisbon, Portugal.
Leader S, et al. Pediatr Infect Dis J. 2002;21(7):629-632.
Karron R. Plotkin’s Vaccines. 7th ed. Philadelphia, PA : Elsevier;2018:943- 949.
Glezen WP, et al. Am J Dis Child. 1986;140(6):543-546.
Hall CB, et al. N Engl J Med. 2009;360(6):588-598.
Hall CB, et al. Pediatrics. 2013;132(2):e341-e348.
Rha B, et al. Pediatrics. 2020;146(1):e20193611.
Hammitt LL, et al. N Engl J Med. 2022;386(9):837-846.
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Healthy preterm infants 32-35 wGA (n=89).png)
Healthy adults aged 18 to 49 years (n=136)
Healthy preterm infants in healthy infants 29-34 weeks 6 days wGA (n=1453)
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Immunocompromised children who are ≤ 24 months of age at the time of dose administration. (n=100).png)
(95% CI, 52.3-81.2)
(95% CI, 51.9-90.3)
(95% CI, 62.9, 95.8)
(95% CI, 16.3-60.5)
(95% CI, 7.1-37.0)
(95% CI, 62.3–85.2)
(95% CI, 49.4–89.4)
(95% CI, 48.8–91.0)
(95% CI, 6.3-60.2)
(95% CI, 23.7-50.0)
(95% CI, 68.5-86.1)
(95% CI, 62.3-90.1)
(95% CI, 68.1-94.0)
(95% CI, 67.7-92.0)
(95% CI, 32.8-92.9)
(95% CI, 39.7-71.2)
