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1173 Safety, Tolerability, and Pharmacokinetics of Nirsevimab for the Prevention of RSV Disease in Immunocompromised Children Aged ≤24 Months: Music, an Open Label, Phase 2 TrialClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 203. Lymphocytes and Acquired or Congenital Immunodeficiency Disorders: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, Viral, Biological therapies, Clinical Research, pediatric, Diseases, neonatal, Infectious Diseases, Therapies, Monoclonal Antibody Therapy, Study Population, Human
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Joseph B Domachowske, MD1*, Ulrika Wählby Hamren2*, Bhanu Basavaraju3*, Anthonet Koen4*, Amanda Leach5*, Vaishali S Mankad6*, Masaaki Mori7*, Carl Ndibmun8*, Pere Soler-Palacin9,10*, Pia S Pannaraj11*, Therese Takas8* and Tonya Villafana8*

1State University of New York Upstate Medical University, Syracuse, NY
2Clinical Pharmacology and Quantitative Pharmacology, R&D, AstraZeneca, Gothenburg, Sweden
3Clinical Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom
4South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
5AstraZeneca, Gaithersburg, MD
6Clinical Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Durham, NC
7Department of Lifetime Clinical Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
8Clinical Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD
9Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Barcelona, Catalonia, Spain
10Vall d’Hebron Research Institute, Barcelona, Catalonia, Spain
11Division of Infectious Diseases, Department of Pediatrics, University of California San Diego, San Diego, CA


Immunocompromised children are at increased risk for severe respiratory syncytial virus (RSV)-associated lower respiratory tract infections (LRTIs), which can lead to poor outcomes, including death. Nirsevimab, an extended half-life monoclonal antibody that targets the RSV prefusion F protein, is approved in Canada, the EU, Great Britain, and the US for the prevention of RSV lower respiratory tract disease in neonates and infants during their first RSV season. In Canada and the US, approval extends to the second season for children remaining at higher risk for severe RSV disease. Here, we present the full analysis of the MUSIC trial (NCT04484935), a 12-month, Phase 2, open-label, uncontrolled, single-dose study of nirsevimab, designed to evaluate the safety, pharmacokinetics (PK), and emergence of antidrug antibodies (ADA) in immunocompromised children ≤24 months of age.


Children aged ≤24 months with ≥1 immunocompromising condition received a single intramuscular injection of nirsevimab 50 mg (if weight <5 kg) or 100 mg (if weight ≥5 kg) prior to their first RSV season or 200 mg if entering their second RSV season (Table 1). Safety, ADA, and PK were evaluated to Day 361 (final database lock April 18, 2023). Adverse events of special interest (AESIs) included immediate hypersensitivity (including anaphylaxis), immune complex disease, or thrombocytopenia.


One hundred children (first RSV season n=46, second RSV season n=54) were enrolled from 8 countries (Table 1). Immunocompromising conditions included primary immunodeficiency (n=33), systemic high-dose corticosteroid therapy, (n=29), immunosuppressive chemotherapy, (n=20), history of organ or bone marrow transplantation (n=16), other immunosuppressive therapy (n=15), and human immunodeficiency virus infection (n=8; children may have had more than one condition). Six children experienced 8 treatment-related adverse events (AEs; pyrexia n=4, abdominal pain n=1, erythema n=1, rash n=2); all were Grade 1 severity , except 1 event of Grade 2 pyrexia, and occurred within 7 days of dosing. No treatment-related serious AEs or new onset chronic diseases were observed. Six AESIs were reported in 5 children; all were Grade 1 hypersensitivity events limited to cutaneous findings (food allergy n=2, contrast media allergy n=1, urticaria n=2, erythema n=1), with 1 considered treatment-related (erythema). Three deaths occurred (LRTI, septic shock, and suspected tumor hemorrhage); all were determined to be unrelated to treatment.

Eleven children developed treatment-emergent ADAs (median titer 200.0; Day 31 n=1, Day 151 n=1, and Day 361 n=9); none experienced a treatment-related serious AE, AESI, or skin hypersensitivity reaction. Of the children who were ADA-positive on Day 361, 1 experienced a treatment-related AE (Grade 1 pyrexia within 60 minutes of dosing), and 1 experienced a Grade 1 rash on Day 104, determined to be unrelated to treatment. Children who were ADA-positive on Day 361 were more likely to have nirsevimab levels below the limit of detection versus ADA-negative children, suggesting an influence of ADA on PK between Days 151 and 361.

Nirsevimab serum exposures at Day 151 were similar to levels demonstrated to be effective in preventing medically attended RSV LRTI in healthy children enrolled in the Phase 3 MELODY trial (Figure 1). Fourteen children demonstrated a rapid decline in serum concentrations through Day 151 compared with the rest of the children; a review of their medical histories revealed evidence for protein-losing conditions, including graft versus host disease, chronic liver disease, and nephrotic syndrome, in 9 of the 14 children.

Although none met protocol-defined case criteria for medically attended RSV LRTI, 3 children had an RSV-positive LRTI (central or local test) requiring medical attendance (in an inpatient or outpatient setting; all after Day 151), of whom 1 was hospitalized.


In immunocompromised children aged ≤24 months, a single dose of nirsevimab was well tolerated and no safety concerns arose over 361 days. Levels of ADA were low, with minimal effects on PK and no apparent impact on safety outcomes. Nirsevimab serum exposure was consistent with previous studies in healthy children and supportive of efficacy in this population at risk of severe RSV disease. Some children with underlying protein-losing conditions had a rapid decline in nirsevimab serum concentrations.

Disclosures: Domachowske: Sanofi: Consultancy, Honoraria; AstraZeneca: Other: Participated in data safety monitoring boards or advisory boards. Wählby Hamren: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Basavaraju: AstraZeneca: Ended employment in the past 24 months. Leach: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Mankad: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Ndibmun: Pharmora Limited: Current Employment, Other: Employee of Pharmora Limited who were contracted to AstraZeneca for this study. Soler-Palacin: Astellas: Research Funding; CSL Behring: Consultancy, Research Funding; Gilead: Research Funding; Grifols: Consultancy, Research Funding; Pfizer: Research Funding; Pharming: Research Funding; Takeda: Consultancy, Research Funding; UCB: Consultancy. Takas: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Villafana: AstraZeneca: Current Employment, Current equity holder in publicly-traded company.

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