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EU CHMP recommends approval of Beyfortus (nirsevimab) for prevention of RSV disease in infants.
EU CHMP recommends approval of Beyfortus (nirsevimab) for the prevention of RSV disease in infants
- The approval opinion is based on the Beyfortus clinical trial results confirming that a single dose of Beyfortus during the RSV epidemic season can effectively prevent lower respiratory tract infections caused by RSV that require medical attention.
- Once approved, Beyfortus will be the first RSV prophylaxis that can be widely used in newborns and infants.
(September 16, 2022, Paris)
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion on Beyfortus (nirsevimab), recommending approval of Beyfortus for use in neonates and infants to help prevent their first respiratory syncytial virus (RSV) infection.
Prevention of RSV lower respiratory tract infection when the epidemic season arrives. Once approved, Beyfortus will be the first and only single-dose passive immunization formulation that can be broadly used in infants, including healthy infants born at term or preterm, or infants with special health conditions. Beyfortus is jointly developed by Sanofi and AstraZeneca.
Jean-François Toussaint , global head of vaccine research and development at Sanofi , said:
“Today’s positive CHMP opinion is one of the most important public health achievements in the field of RSV in decades, and promises to reduce the enormous physical and psychological burden that RSV places on families and healthcare systems. Our goal is to deliver a single dose to all infants Providing RSV prevention, CHMP certainly means we are one step closer to that goal.”
Iskra Reic , executive vice president of vaccines and immunotherapy at AstraZeneca , said:
“The CHMP’s positive opinion underscores the potential of Beyfortus to be a landmark, first-of-its-kind passive immunization formulation and to revolutionize the way the entire medical community prevents RSV in the infant population.”
CHMP’s positive opinion is based on the results of Beyfortus clinical studies, including Phase III MELODY, Phase II/III MEDLEY and Phase IIb clinical studies1-8 . In the MELODY and Phase IIb studies, Beyfortus met its primary endpoint of reducing RSV-induced lower respiratory tract infections (LRTIs) during RSV season with a single dose of Beyfortus compared to placebo1-6 . The safety profile of Beyfortus was similar to placebo. In the Phase II/III MEDLEY study, Beyfortus also demonstrated a safety and tolerability profile comparable to that of Palivizumab 7-8 .
Respiratory syncytial virus is the most common cause of lower respiratory tract infection and the leading cause of hospitalization in infants worldwide, with the majority of hospitalizations occurring in healthy term infants 9-13 . The global direct medical costs associated with RSV (including inpatient, outpatient and follow-up care) were estimated at EUR 4.82 billion in 2017 14 . Currently, there is no preventive regimen for all infants, and treatment is limited to symptom relief15,16 .
Beyfortus (nirsevimab) is an investigational long-acting monoclonal antibody designed for all infants to protect against RSV disease from birth to the first RSV season with a single dose injection, jointly developed by Sanofi and AstraZeneca R&D.
Beyfortus directly helps neonates and infants prevent RSV-related lower respiratory tract infections by administering antibodies to them. Unlike active immune mechanisms that require activation of the human immune system, monoclonal antibodies provide timely, rapid, and immediate immune protection17 .
In March 2017, Sanofi and AstraZeneca announced an agreement to jointly develop and commercialize Beyfortus.
Under the terms of this agreement, AstraZeneca will be responsible for all R&D and production activities, while Sanofi will be responsible for commercialization and revenue measurement.
Under the terms of the agreement, Sanofi has paid an upfront payment of 120 million euros, a research and development milestone fee of 30 million euros, and will make further payments of up to 465 million euros upon the achievement of certain research and development and sales milestones.
Both companies share all costs and profits. The revenue involved in the agreement will be reported as partnership revenue in the company’s financial statements.
Beyfortus has been granted accelerated development status by multiple regulatory agencies around the world.
These include the “Breakthrough Therapy Drug Program” granted by the Center for Drug Evaluation (CDE) of the State Drug Administration of China; the Breakthrough Therapy Designation granted by the U.S. Food and Drug Administration (FDA);
The Medicines Scheme (PRIority Medicines); the UK Medicines and Healthcare Products Regulatory Agency’s (MHRA) granting “Breakthrough Innovative Medicines” designation;
“Priority Drug Development”.
The safety and efficacy of Beyfortus were reviewed under the EMA’s accelerated review process and have not yet received formal approval from the regulatory agency.
About clinical research
The Phase IIb clinical study is a randomized, placebo-controlled study evaluating the efficacy of Beyfortus (nirsevimab) in the prevention of RSV-associated lower respiratory tract infections requiring medical attention within 150 days of injection.
In the study, healthy preterm infants aged 29-35 weeks were randomly assigned in a 2:1 ratio to receive a single intramuscular dose of 50 mg of Beyfortus or a placebo.
The study met its primary endpoint of being able to reduce RSV-related lower respiratory tract infections requiring a doctor visit by 70.1% compared to placebo (95% CI: 52.3, 81.2).
Between November 2016 and December 2017, at the beginning of the RSV season, 1453 infants were randomly assigned to Beyfortus or placebo (Beyfortus, n=969; placebo, n=484).
Studies were conducted in 164 centres in 23 countries in the northern and southern hemispheres3,4 .
Study data were published in the New England Journal of Medicine (NEJM) in July 2020.
The MELODY study is a randomized, placebo-controlled Phase III clinical study in 21 countries to evaluate healthy late preterm and term infants (gestational age ≥35 weeks) entering the first RSV epidemic season, The endpoint of the study was confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) compared to placebo in the prevention of RSV -associated lower respiratory tract infection requiring medical attention within 150 days after injection of Beyfortus1,2 .
The study met the primary endpoint of a 74.5% (95% CI 49.6, 87.1; P<0.001) reduction in hospital visits for RSV-related acute lower respiratory tract infections (eg, bronchiolitis or pneumonia) with a single dose of Beyfortus compared with placebo.
Infants were randomized 2:1 to receive a single intramuscular dose of 50 mg (infants weighing <5 kg) or 100 mg (infants weighing ≥5 kg) of Beyfortus or placebo.
Between July 2019 and March 2020, 1490 infants were randomized to receive Beyfortus or placebo at the beginning of the RSV season .
Data from the primary analysis were published in the New England Journal of Medicine in March 2022.
The results of the Beyfortus-related clinical studies included a prespecified pooled analysis of the Phase III MELODY study and the recommended doses of the Phase IIb clinical study.
Results of the analysis showed that Beyfortus reduced the risk of lower respiratory tract infections requiring medical attention (such as bronchitis and pneumonia) in term and preterm infants entering the first RSV season by 79.5% (95%) compared to placebo. CI 65.9, 87.7; P<0.0001) 5 .
Healthy preterm and term infants in the pooled analysis were injected with recommended doses of Beyfortus based on body weight. RESULTS: At 151 days, Beyfortus was 77.3% (95% CI 50.3, 89.7; P<0.001) effective at the recommended dose in reducing hospitalizations for RSV-related lower respiratory tract infection in healthy preterm and term infants.
The findings were published in March 2022 in the New England Journal of Medicine 1,5 .
MEDLEY is a Phase II/III, randomized, double-blind, controlled clinical study with palivizumab, the primary objective of which is to compare Beyfortus with palivizumab in preterm infants, infants with congenital heart disease and/or or safety and tolerability in infants with chronic lung disease 7,8 .
Between July 2019 and May 2021, approximately 918 infants entering the first RSV season were randomized to a single intramuscular dose of 50 mg (infants weighing <5 kg) or 100 mg (infants weighing ≥5 kg).
Beyfortus group or Palivizumab group. Safety was assessed by monitoring the incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) within 360 days after injection7,8 .
The serum concentrations of nirsevimab in this study (day 151) were comparable to the results of the phase III MELODY study, suggesting that the protective effect of nirsevimab in this population may be similar to that of healthy term and late preterm infants 7 . The findings were published in the New England Journal of Medicine in March 2022.
Based on the results of the MELODY Phase III and MEDLEY Phase II/III and Phase IIb clinical studies, a single dose of Beyfortus provided sustained protection in all infants throughout the RSV season 1-8 .
All infants include preterm infants, healthy late preterm and term infants, and infants with special health conditions.
The results of these studies are the cornerstone of submissions to regulators starting in 2022.
About Respiratory Syncytial Virus (RSV)
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in infants, including bronchiolitis and pneumonia 9 .
RSV is also the leading cause of hospitalization in infants worldwide, with the majority of hospitalizations occurring in healthy term infants 10-13 .
In 2019, there were approximately 33 million cases of RSV-associated acute lower respiratory tract infection in children under 5 years of age worldwide, resulting in more than 3 million hospitalizations and an estimated 26,300 children’s hospital deaths18 .
The global direct medical costs associated with RSV (including inpatient, outpatient and follow-up care) were estimated at EUR 4.82 billion in 2017 14 .
1. Hammitt LL, MD et al. Nirsevimab for Prevention of RSV in Healthy Late -Preterm and Term Infants. N Engl J Med. 2022;386(9): 837-846. doi: 10.1056/NEJMoa2110275.
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 September 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 September 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.
5. Simões, E, et al. Pooled efficacy of nirsevimab against RSV lower respiratory tract infection in preterm and term infants. ESPID 2022 Congress; 2022 May 9-13. Hybrid Congress.
6. Wilkins, D, et al. Nirsevimab for the prevention of respiratory syncytial virus infection: neutralizing antibody levels following a single dose. ESPID 2022 Congress; 2022 May 9-13. Hybrid Congress.
7. Domachowske J, MD et al. Safety of Nirsevimab for RSV in Infants with Heart or Lung Disease or Prematurity. N Engl J Med. 2022; 386 (9).
8. 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 (MEDLEY). Accessed September 2022.
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11. McLaurin KK, Farr AM, Wade SW, Diakun DR, Stewart DL. Respiratory syncytial virus hospitalization outcomes and costs of full-term and preterm infants. Journal of Perinatology: official journal of the California Perinatal Association. 2016;36(11) :990-6.
12. Rha B, et al. Respiratory Syncytial Virus-Associated Hospitalizations Among Young Children: 2015-2016. Pediatrics. 2020;146:e20193611.
13. Arriola CS, et al. Estimated Burden of Community-Onset Respiratory Syncytial Virus-Associated Hospitalizations Among Children Aged <2 Years in the United States, 2014-15. J Pediatric Infect Dis Soc. 2020;9:587-595
14. Zhang S, et al. Cost of Respiratory Syncytial Virus-Associated Acute Lower Respiratory Infection Management in Young Children at the Regional and Global Level: A Systematic Review and Meta-Analysis. J Infect Dis. 2020;222(Suppl 7): S680-687.
15. Villafana T, et al. Passive and active immunization against respiratory syncytial virus for the young and old. Expert Rev Vaccines. 2017;16:1-39.
16. Respiratory Syncytial Virus Infection (RSV): Infants and Young Children. Centers for Disease Control and Prevention. https://www.cdc.gov/rsv/high-risk/infants-young-children.html. Accessed September 2022.
17. Centers for Disease Control and Prevention. Vaccines & Immunizations. August 18, 2017. https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm. Accessed September 2022.
18. Li Y, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis. Lancet 2022;399:92047–64.
(source:internet, reference only)