Drug name
Nirsevimab
Developer(s)
Drug information
Not provided
Nirsevimab
Beyfortus
Biotherapeutic
Nirsevimab (MEDI8897) is a recombinant human IgG1 kappa monoclonal antibody used for the treatment of Respiratory Syncytial Virus (RSV), which is a major cause of acute lower respiratory infection and hospitalisation in young children and infants. Nirsevimab acts to block viral entry into the host cell by targeting the RSV fusion (F) protein and binding to a highly conserved epitope located within the F1 and F2 subunits. Nirsevimab neutralises RSV-A and -B strains with >50-fold greater efficacy than palivizumab and possesses an extended half-life (68.7±10.9 days) through the introduction of a triple amino acid substitution (YTE) in the Fc region. Given its favourable safety profile, nirsevimab may provide a cost-effective option for RSV prophylaxis that supports once-per-season IM dosing.
Beyfortus (nirsevimab-alip) (100 mg/mL), available in 0.5 mL and 1 mL extended-release single-dose intramuscular injections, has been approved by several regulatory authorities for the prevention of lower respiratory tract disease caused by Respiratory Syncytial Virus (RSV) in neonates and infants during their initial RSV season and for children up to 24 months of age. These approvals have been granted in multiple regions, including the United States, Australia, the European Union countries, Switzerland, the United Kingdom, Saudi Arabia, Qatar, China, and Japan. Real world data from countries such as the US, Spain and France have confirmed and even surpassed the outstanding efficacy data generated during the clinical development of this monoclonal antibody.
Beyfortus has received Fast Track Designation from the USFDA and European Marketing Authorisation from EMA. It was first approved by EMA and the UK in the year 2022 followed by other countries. Beyfortus has now been launched in more than 20 countries. Many more countries are expected to implement all-infant protection in the future.
Therapeutic area(s)
- Respiratory syncytial virus (RSV)
- Prevention
Administration route
Intramuscular
Associated long-acting platforms
Monoclonal antibodies and antibody drug conjugates
Use of drug
- Administered by a nurse
- Administered by a specialty health worker
- Administered by a community health worker
Not provided
Dosage
Solution for injection in pre-filled syringes with 50 mg in 0.5 ml and 100 mg in 1 ml (100 mg/ml)
Single dose. For toddlers who remain vulnerable to severe RSV disease after the first immunisation with Beyfortus, the paediatrician will recommend a further dose in the second RSV season.
The recommended dose is a single dose of 200 mg, administered as two intramuscular injections (2 x 100 mg)
The recommended dose for infants weighing less than 5 kg is a single dose of 50 mg. For infants weighing 5 kg or more, the recommended single dose is 100 ml
For toddlers who remain vulnerable to severe RSV disease after the first immunisation with Beyfortus, the paediatrician will recommend a further dose in the second RSV season. The recommended dose is
Associated technologies
Not provided
Comment & Information
Developer(s)
AstraZeneca plc (AZ), is a British-Swedish multinational biopharmaceutical company headquartered in Cambridge, UK. Their product portfolio targets a diverse array of pathologies, including oncology, cardiovascular diseases, gastrointestinal conditions, infectious agents and neurological disorders. Notably, they partnered with Oxford University to develop the ChAdOx1 nCoV-19 vaccine.
Sanofi S.A. is a leading French multinational pharmaceutical and healthcare company headquartered in Paris, France. Established in 1973, Sanofi researches, develops, manufactures and markets of a broad portfolio of pharmaceutical products encompassing several therapeutic areas, including: diabetes, internal medicine, cardiovascular disease, neurology, oncology, thrombosis and vaccines.
Drug structure
Scale-up and manufacturing prospects
General manufacturing requirements and production scale-up for therapeutic monoclonal antibody (mAb) products is primarily focused on pharmacokinetic suitability, formulation stability and the overall maintenance of product quality. Industrial bioprocessing steps can also potentially introduce additional challenges regarding mAb formulation viscosity and aggregation propensity.
Industrial bioreactor vessel with a production volume capacity of between 5-25kL. Continuous disc stack centrifuges for bioreactor harvesting with subsequent membrane and depth filtration for supernatant clarification. Recombinant protein-A chromatography or other suitable affinity capture apparatus followed by two chromatographic polishing steps such as cation- and anion-exchange. Ultrafiltration membrane system to concentrate and formulate the final product.
monoclonal antibodies are highly dependent on their structural, chemical and conformational stability for biological activity. Chemical degradation of mAbs during manufacture can lead to the generation of product variants and complex impurity profiles resulting from a wide range of processes, including: N-linked glycosylation, isomerisation, fragmentation, deamidation, oxidation and C-terminal lysine clipping. Additionally prior to packaging, the final product requires close monitoring for the presence of residual contaminants such as endotoxins and pro-inflammatory peptidoglycans.
Formulation characterisation steps for therapeutic mAb products include (but are not limited to): (1) Identification of post-translational modifications using ion-exchange chromatography and capillary isoelectric focusing, (2) Measurement of concentration dependent aggregation rates via thermal differential scanning calorimetry, sub-visible particle quantitation and size-exclusion chromatography, and (3) Antibody clipping and fragmentation detection by capillary electrophoresis.
Excipients
No proprietary excipient used
No novel excipient or existing excipient used
No residual solvent used
Delivery device(s)
No delivery device
Publications
Keam SJ. Nirsevimab: First Approval. Drugs. 2023 Feb;83(2):181-187. doi: 10.1007/s40265-022-01829-6. PMID: 36577878.
Nirsevimab (Beyfortus®), a long-acting intramuscular recombinant neutralising human IgG1ĸ monoclonal antibody to the prefusion conformation of the respiratory syncytial virus (RSV) F protein that has been modified with a triple amino acid substitution in the Fc region to extend the serum half-life, is being jointly developed by AstraZeneca and Sanofi for the prevention of RSV disease. The extended serum half-life allows administration of nirsevimab as a single dose to cover the RSV season. Nirsevimab was approved in the EU on 3 November 2022 and in the UK on 7 November 2022 for the prevention of RSV lower respiratory tract disease in neonates and infants during their first RSV season. This article summarizes the milestones in the development of nirsevimab leading to this first approval for the prevention of RSV disease in all infants.
Moline HL, Tannis A, Toepfer AP, et al. Early Estimate of Nirsevimab Effectiveness for Prevention of Respiratory Syncytial Virus–Associated Hospitalization Among Infants Entering Their First Respiratory Syncytial Virus Season — New Vaccine Surveillance Network, October 2023–February 2024. MMWR Morb Mortal Wkly Rep 2024;73:209–214. DOI: http://dx.doi.org/10.15585/mmwr.mm7309a4
Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States. In August 2023, CDC’s Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, for infants aged <8 months to protect against RSV-associated lower respiratory tract infection during their first RSV season and for children aged 8–19 months at increased risk for severe RSV disease. In phase 3 clinical trials, nirsevimab efficacy against RSV-associated lower respiratory tract infection with hospitalization was 81% (95% CI = 62%–90%) through 150 days after receipt; post-introduction effectiveness has not been assessed in the United States. In this analysis, the New Vaccine Surveillance Network evaluated nirsevimab effectiveness against RSV-associated hospitalization among infants in their first RSV season during October 1, 2023–February 29, 2024. Among 699 infants hospitalized with acute respiratory illness, 59 (8%) received nirsevimab ≥7 days before symptom onset. Nirsevimab effectiveness was 90% (95% CI = 75%–96%) against RSV-associated hospitalization with a median time from receipt to symptom onset of 45 days (IQR = 19–76 days). The number of infants who received nirsevimab was too low to stratify by duration from receipt; however, nirsevimab effectiveness is expected to decrease with increasing time after receipt because of antibody decay. Although nirsevimab uptake and the interval from receipt of nirsevimab were limited in this analysis, this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.
Additional documents
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