Global Phase 3 Trial Results Show Nirsevimab Significantly Protects Infants Against Respiratory Syncytial Virus Infection
Sanofi
Pharmaceutical R&D Developer
AstraZeneca
Biopharmaceutical Manufacturer
ShanghaiMarch 3, 2022 /PRNewswire/ -- The New England Journal of Medicine, an internationally authoritative medical journal, published today a preventive monoclonal antibodynirsevimabDetailed results of Phase III clinical trials,nirsevimabIs the first investigational long-acting antibody that provides sustained protection for all infants throughout the Respiratory Syncytial Virus (RSV) season with just a single injection. The trial enrolled full-term infants or late preterm infants (gestational age 35 weeks or more) entering their first RSV season and met its primary endpoint. Study results showed that, compared to placebo, a single dose...nirsevimabThe efficacy rate of protecting infants from lower respiratory tract infections (such as bronchiolitis or pneumonia) caused by respiratory syncytial virus that require medical attention reached 74.5%, which was statistically significant (95% CI 49.6 to 87.1; p<0.001).[1,2]。
Researchers also conducted a pre-specified pooled analysis of hospitalizations caused by respiratory syncytial virus in Phase III and IIb trials. The results showed that nirsevimab, at the recommended dose, reduced RSV-related hospitalization rates by 77.3% (95% CI 50.3 to 89.7, P<0.001) in full-term and preterm infants (gestational age greater than 28 weeks).[1-3]。Only in the MELODY trial, investigators observed a reduction in the number of patients hospitalized due to respiratory syncytial virus infection (62.1%, 95% CI: -8.6% to 86.8%; P=0.07).[1,2]，In the nirsevimab group, 6 of 994 infants were hospitalized for lower respiratory tract infections caused by respiratory syncytial virus, compared with 8 of 496 infants in the placebo group.[1,2]。
Associate Professor of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USADr. William Muller, Director of Clinical and Community Trials Sciences at Ann & Robert H. Lurie Children's Hospital, stated: As various public health measures for COVID-19 are gradually relaxed, we are seeing a rebound in Respiratory Syncytial Virus (RSV) infections, indicating the need for a broad immunization approach to help reduce the significant burden RSV infections place on infants, their families, and the healthcare system. These exciting research findings show that nirsevimab has the potential to protect all infants from RSV, which would represent a major shift in the current landscape of disease prevention.
Based on the results of Phase III and II/III clinical trials as well as Phase IIb clinical trials, it has been confirmed that a single dose of nirsevimab can provide continuous protection for all infants throughout the RSV season.[1-6]
Global Head of Vaccine R&D at SanofiJean-FrançOis Toussaint stated, "In these three pivotal late-stage clinical trials, we focused on researching preventive measures for respiratory syncytial virus for all infants, as a first-in-class solution. The Phase III MELODY clinical results for healthy late preterm and full-term infants represent a significant milestone in achieving this goal. We are very pleased."nirsevimab"Expected to become the first preventive measure that requires only a single injection to provide continuous protection for all infants during the RSV season."
Expected to provide rapid protection
Nirsevimab is the first investigational long-acting antibody designed to protect all infants during their first respiratory syncytial virus (RSV) season. The goal is to provide infants with quick and direct protection through a single immunization dose of nirsevimab. Nirsevimab is the first investigational preventive monoclonal antibody to demonstrate protection of infants from RSV in a Phase III clinical trial.[1,2]。Respiratory syncytial virus is the most common cause of lower respiratory tract infections, including bronchiolitis and pneumonia, in all infants, and is the leading cause of infant hospitalization.[7-9]。
Professor Shen Kunling, Advisor of the National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital affiliated to Capital Medical University, and Shenzhen Children's Hospital, stated that respiratory syncytial virus (RSV) is highly contagious, similar to the novel coronavirus, and all infants and young children are at risk of infection. Currently, in the field of RSV prevention and treatment in China, there are no effective drugs or preventive measures available. We look forward to the early market launch of nirsevimab, a monoclonal antibody for prevention, to fill a major gap in RSV infection prevention. It is hoped that the progress of related clinical trials in China will be accelerated, gaining early approval to enter the vaccination system, benefiting all infants and young children in China.
PreventionClinical studies on the monoclonal antibody nirsevimab have been conducted in more than 30 countries worldwide. A Phase III clinical study targeting healthy infants in China has also been initiated. Global marketing applications were launched in the first half of 2022.
Sanofi Pasteur and its partner AstraZeneca are working together with all parties to promote the development and market launch of nirsevimab in China, protecting millions of Chinese infants from respiratory syncytial virus (RSV) infection.
About the Phase III MELODY Clinical Trial
MELODY is a randomized, placebo-controlled Phase III clinical trial conducted across 21 countries/regions. The trial enrolled healthy infants entering their first respiratory syncytial virus (RSV) season to evaluate the incidence of RSV-caused lower respiratory tract infections (LRTI) requiring medical attention within 150 days post-injection in the nirsevimab group compared to the placebo group, as confirmed by reverse transcription polymerase chain reaction (RT-PCR).[1,2]Healthy late preterm infants (35 weeks gestational age or greater) and full-term infants were randomly assigned (2:1) to receive a single intramuscular dose of nirsevimab, 50 mg for infants weighing <5 kg or 100 mg for infants weighing ≥5 kg, or placebo.
From July 2019 to February 2021, 1,490 infants were randomly assigned to receive nirsevimab or placebo at the start of the RSV season.[1,2]Based on a hierarchical testing strategy protected by multiplicity, the researchers pre-specified a pooled analysis of RSV LRTI hospitalization endpoints from the MELODY and Phase 2b clinical trials. The overall safety profile of nirsevimab in this trial was consistent with previously reported results. In the MELODY and Phase 2b clinical trials, there were no clinically meaningful differences in safety outcomes between the nirsevimab group and the placebo group.[1-3]。
The assessment process for the primary endpoint of the MELODY trial is ahead of schedule. During the COVID-19 pandemic, public health measures taken by countries around the world reduced the transmission of all respiratory viruses, including RSV, at the time of trial registration. Researchers had already accumulated enough cases before the outbreak to evaluate the ability of nirsevimab compared to placebo in preventing lower respiratory tract infections caused by respiratory syncytial virus. Trial sites in both the Northern and Southern Hemispheres have additionally enrolled 1,500 infants to provide more safety information.[1,2]。
About Respiratory Syncytial Virus (RSV)
Respiratory Syncytial Virus (RSV) is a common contagious virus that causes seasonal epidemics of lower respiratory tract infections (LRTI), including bronchiolitis and pneumonia.[10-12]RSV is also the leading cause of global infant hospitalization.[8,9]In 2015, there were approximately 30 million new cases of RSV-related lower respiratory tract infections globally, resulting in over 3 million hospitalizations and about 60,000 in-hospital deaths of children under the age of five.[12,13]In recent months, with the gradual easing of public health policies related to COVID-19, RSV has rebounded.[14,15]Most RSV-related hospitalization cases occur in healthy infants born at full term.[16,17]In addition, patient visits due to lower respiratory tract infections have increased the cost burden on the entire healthcare system.[18]。
About Nirsevimab
Nirsevimab is an investigational long-acting antibody that protects all infants experiencing their first RSV season through a single injection. Based on extended half-life technology, nirsevimab can be administered as a single dose to all infants going through their first RSV season, as well as to those with specific conditions such as congenital heart disease or chronic lung disease during their first and second RSV seasons.[2,6,19]。
Nirsevimab adopts a passive immune mechanism, directly helping infants and young children prevent diseases related to respiratory syncytial virus infection by administering antibodies. Unlike active immune mechanisms, which require activation of the human immune system to combat viral infections, the passive immune mechanism of monoclonal antibodies can provide rapid and direct immune protection.[20]。
Nirsevimab has been granted accelerated development status by multiple authoritative regulatory agencies worldwide, including the "Breakthrough Therapy Designation" from the Center for Drug Evaluation of China's National Medical Products Administration; the "Breakthrough Therapy" designation from the U.S. Food and Drug Administration; the "Priority Medicines (PRIME)" program from the European Medicines Agency; and the "Breakthrough Innovative Medicine" qualification from the UK Medicines and Healthcare products Regulatory Agency (MHRA). Additionally, it has been selected as a "Priority Development Drug" under the Japan Agency for Medical Research and Development (AMED)’s "Research Program for Selection of Drugs to Promote Development of New Pediatric Medicines."
References:
1. Hammitt LL, MD et al. (2021). Single-dose Nirsevimab for Prevention of Respiratory Syncytial Virus in Healthy Late Preterm and Term Infants. New England Journal of Medicine. Manuscript submitted for publication.
2. Clinicaltrials.gov. A Study to Evaluate the Safety and Efficacy of MEDI8897 for the Prevention of Medically Attended RSV LRTI in Healthy Late Preterm and Term Infants (MELODY). https://clinicaltrials.gov/ct2/show/NCT03979313. Accessed February 2022.
3. Clinicaltrials.gov. A Study to Evaluate the Safety and Efficacy of MEDI8897 for the Prevention of Medically Attended RSV LRTI in Healthy Preterm Infants. (MEDI8897 Ph2b). https://clinicaltrials.gov/ct2/show/results/NCT02878330. Accessed February 2022.
4. Griffin P, MD et al. (2020). Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants. NEJM 2020; 383: 415-425. DOI: 10.1056/NEJMoa1913556. Accessed February 2022.
5. MEDLEY Article [reference to be adjusted] New England Journal of Medicine. Article submitted for publication.
6. Clinicaltrials.gov. A Study to Evaluate the Safety of MEDI8897 for the Prevention of Medically Attended Respiratory Syncytial Virus (RSV) Lower Respiratory Track Infection (LRTI) in High-risk Children. https://clinicaltrials.gov/ct2/show/NCT03959488.
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13. Oxford Vaccines Group. What is RSV? https://vk.ovg.ox.ac.uk/vk/rsv. Accessed February 2022.
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15. CDC Health Alert Network. Increased Interseasonal Respiratory Syncytial Virus (RSV) Activity in Parts of the Southern United States. Centers for Disease Control and Prevention. June 10 2021. https://emergency.cdc.gov/han/2021/han00443.asp Accessed February 2022.
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17. Arriola CS, Kim L, Langley G, Anderson EJ, Openo K, Martin AM, et al. Estimated Burden of Community-Onset Respiratory Syncytial Virus-Associated Hospitalizations Among Children Aged <2 Years in the United States, 2014-15. Journal of the Pediatric Infectious Diseases Society. 2020;9(5):587-95.
18. Leistner R, et al. “Attributable Costs of Ventilator-Associated Lower Respiratory Tract Infection (LRTI) Acquired on Intensive Care Units: a Retrospectively Matched Cohort Study.” Antimicrobial Resistance and Infection Control, vol. 2, no. 1, 4 Apr. 2013, p. 13., doi:10.1186/2047-2994-2-13
19. Zhu Q, et al. A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants. Sci Transl Med. 2017;9:pii: eaaj1928
20. Centers for Disease Control and Prevention. Vaccines & Immunizations. August 18, 2017. https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm. Accessed February 2022.