Article
Source: Campus Sanofi
May 20, 2025

Nirsevimab : Clinical Experience

Author: Sanofi

Editorial Team

Study Design

Preclinical trials

2014

Phase 1a¹
NCT02114268

“1^st Time in Healthy Adults”

Healthy adults aged 18 to 49 years (n=136)

Evaluation of pharmacokinetics and safety profile of Nirsevimab before initiating a clinical study in infants

Phase 1b/2a²
NCT02290340

“1^stTime in Healthy Preterm Infants”

Healthy preterm infants 32-35 wGA (n=89)

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”

Healthy preterm infants in healthy infants 29-34 weeks 6 days wGA (n=1453)

Evaluation of nirsevimab for the prevention of RSV-associated lower respiratory tract infection in healthy infants

2019

Phase 3^4,5
NCT03979313

Healthy late preterm and term infants ≥ 35 wGA (n=3012)

Evaluation of efficacy and safety of nirsevimab in healthy late-preterm and term infants entering their first RSV season

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 2/3^6-8
NCT03959488

‘MEDLEY’

Preterm cohort
(n=615)

Evaluation of safety of nirsevimab in preterm infants with OR without CHD or CLD of prematurity

2019

Season 2^†(n=262)

CHD/CLD cohort
(n=310)

2020

Phase 2^9,31
NCT04484935

‘MUSIC’

Immunocompromised children who are ≤ 24 months of age at the time of dose administration. (n=100)

Evaluation of safety and tolerability, for nirsevimab in immunocompromised children

2022

Phase 3^b10
NCT05437510

‘HARMONIE’

Healthy infants ≥29 wGA not eligible for palivizumab (n=8058)

Determination of efficacy and safety of nirsevimab for the prevention of hospitalizations due to RSV-LRTI in all palivizumab ineligible infants under 12 months

Key results from the clinical development program of nirsevimabs

Safety

Nirsevimab (N=3580): Favorable Safety Profile Across All Infants in pivotal studies

		Variables	Serious adverse events	Adverse events of Grade 3 or higher	Adverse events of special interest (AESI)	Deaths
Ph2b³ 29-<35 wGA		Placebo (N=479)	16.9%	12.5%	0.6%	3
Ph2b³ 29-<35 wGA		Nirsevimab (N=968)	11.2%	8.0%	0.5%	2
MELODY⁴ ≥35 wGA		Placebo (N=996)	7.4%	3.8%	0.0%	0
MELODY⁴ ≥35 wGA		Nirsevimab (N=1998)	6.3%	3.1%	0.2%	4
MEDLEY First season⁶	Preterm	Palivizumab (N=206)	5.3%	3.4	0.0%	0
	Preterm	Nirsevimab (N=406)	6.9%	3.4%	0.2%	2
	CHD/CLD	Palivizumab (N=98)	20.4%	13.3%	0.0%	1
	CHD/CLD	Nirsevimab (N=208)	19.2%	14.4%	0.5%	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

	HARMONIE^10,11		MUSIC⁹	MEDLEY Second season¹²
	HARMONIE^10,11		MUSIC⁹	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 2b^3,15	70.1% (95% CI, 52.3-81.2)	78.4% (95% CI, 51.9-90.3)	87.5% (95% CI, 62.9, 95.8)	42.5% (95% CI, 16.3-60.5)	23.5% (95% CI, 7.1-37.0)
MELODY STUDY All	76.4% (95% CI, 62.3–85.2)	76.8% (95% CI, 49.4–89.4)	78.6% (95% CI, 48.8–91.0)	38.9% (95% CI, 6.3-60.2)	38.2% (95% CI, 23.7-50.0)
Phase 2b + MELODY STUDY All (Pooled)⁵	79.0% (95% CI, 68.5-86.1)	80.6% (95% CI, 62.3-90.1)	86.2% (95% CI, 68.1-94.0)
HARMONIE STUDY¹⁰		83.2% (95% CI, 67.7-92.0)	75.7% (95% CI, 32.8-92.9)	58.0% (95% CI, 39.7-71.2)

All infants need protection from RSV^16-21.

Nirsevimab is designed to provide protection for all infants for the length of typical RSV season with a single dose^3,22.

Nirsevimab has demonstrated an efficacy of 79% against RSV-MA-LRTI (MELODY/Ph2b pooled), and 83% against hospitalizations (HARMONIE), for 150 days^5,10.

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 season^23-25.

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

Abbreviations

Useful Links

References

Griffin MP, et al. Antimicrob Agents Chemother. 2017;61(3):e01714-16.
Domachowske JB, et al. Pediatr Infect Dis J. 2018;37(9):886-892.
Griffin MP, et al; N Engl J Med. 2020;383(5):415-425.
Muller WJ, et al. N Engl J Med. 2023;388(16):1533-1534.
Nirsevimab for the prevention of RSV in all infants Accessed October 2023.
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.
Sanofi presentation to US Advisory Committee on Immunization Practices. 20 October 2022. Accessed October 2023.
FDA approves Beyfortus™(nirsevimab-alip) to protect infants against RSV disease. Accessed October 2023.
European Medicines Agency. Nirsevimab. EMEA/H/C/005304. Accessed October 2023.
Medicines & Healthcare products Regulatory Agency (MHRA). MHRA- 100067-PIP01-21-M01. Accessed October 2023.
Health Canada approves BEYFORTUS™ (nirsevimab) for the prevention of RSV disease in infants Accessed October 2023.
Jones JM, et al. MMWR Morb Mortal Wkly Rep. 2023;72(34):920-925.
HAS | BEYFORTUS (nirsevimab) - Respiratory syncytial virus Accessed October 2023.
Recomendaciones de utilización de nirsevimab frente a virus respiratorio sincitial para la temporada 2023-2024 Accessed October 2023.
History of Changes for Study - NCT04484935 Accessed October 2023.

MAT-SA-2400215-V1-April 2024

Study Design

Preclinical trials

2014

Pivotal clinical trials

Key results from the clinical development program of nirsevimabs

Key results from the clinical development program

NITAGs Recommend Nirsevimab for All Infants

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