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Beyfortus (Nirsevimab) RSV Antibody

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February 15, 2024
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Beyfortus™ (Nirsevimab) RSV Monoclonal Antibody 2024

Beyfortus™ (Nirsevimab-alip) (MEDI8897) is the first Approved extended half-life monoclonal antibody (mAb) offering passive immunization to prevent lower respiratory tract infections (LRTI) caused by the respiratory syncytial virus (RSV). Beyfortus binds to the prefusion conformation of the RSV fusion protein. Beyfortus is designed to protect infants experiencing their first or second RSV season and those with congenital heart disease or chronic lung disease. Beyfortus was developed in partnership between AstraZeneca and Sanofi using AstraZeneca's YTE technology.

In June 2021, the World Health Organization (WHO) published preferred product characteristics (June 2022) for long-acting mAbs for passive immunization against RSV disease in infants and children. Beyfortus was approved in the European Union (EU) on November 4, 2022, to prevent lower respiratory tract disease in newborns and infants during their first RSV season. The EU approval was based on results from the clinical development program, including the MELODY Phase III, MEDLEY Phase II/III, and Phase IIb trials, and follows the recommendation by The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) PRIority MEdicines scheme in September 2022. 

The JAMA Network published an Orginal Investigation on February 17, 2023, suggesting Beyfortus is associated with substantial benefits in preventing RSV infection in children. The peer-reviewed New England Journal of Medicine (NEJM) published a Correspondence on April 5, 2023, Nirsevimab for Prevention of RSV in Term and Late-Preterm Infants, and published a different Correspondence on March 3, 2022: Safety of Nirsevimab for RSV in Infants with Heart or Lung Disease or Prematurity, that found at day 151, serum levels of nirsevimab were similar in the two cohorts and similar to those reported in the MELODY phase 2/3 clinical trial. The phase 3 clinical study Understanding Pre-Exposure Prophylaxis of NOVel Antibodies (SUPERNOVA) was last updated on April 3, 2023.

On May 12, 2023, Sanofi announced new data from the HARMONIE Phase 3b clinical trial show an 83.21% (95% CI 67.77 to 92.04; P<0.001) reduction in hospitalizations due to RSV-related LRTD in infants under 12 months of age who received a single dose of Beyfortus, compared to infants who received no RSV intervention. In addition, the data from HARMONIE also show that nirsevimab reduced the incidence of hospitalizations due to severe RSV-related LRTD (patients whose oxygen level is under 90% and require oxygen supplementation) by 75.71% (95% CI 32.75 to 92.91; P<0.001), and demonstrated a reduction of 58.04% in the incidence of all-cause LRTD hospitalization compared to infants who received no RSV intervention. On December 28, 2023, results (0.3% who received nirsevimab were hospitalized for RSV-associated lower respiratory tract infection compared with 1.5% of those who received standard care) from the HARMONIE clinical study indicated that Beyfortus protected infants against hospitalization for RSV-associated LRTD and against very severe RSV-associated lower respiratory tract infection in conditions that approximated real-world settings.

On July 17, 2023, the U.S. Food and Drug Administration (FDA) Approved Beyfortus™ for the prevention of RSV LRTD in newborns and infants born during or entering their first RSV season and for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. Beyfortus may become available in the U.S. before the 2023-2024 RSV season. On August 25, 2023, the U.S. Centers for Disease Control and Prevention (CDC) issued a Morbidity and Mortality Weekly Report stating that based on pandemic patterns, Beyfortus could be administered in most of the continental U.S. from October through the end of March. On September 5, 2023, the U.S. CDC published Health Advisory CDCHAN-00498, encouraging clinicians to prepare to implement mAb products, including Beyfortus. On October 23, 2023, the CDC published Interim Recommendations to Protect Infants from RSV (CDCHAN-00499) during the 2023–2024 season. On October 26, 2023, the CDC hosted a COCA webinar - Protecting Infants from RSV; about 2–3% of young infants will be hospitalized for RSV. On January 4, 2024, the CDC advised healthcare providers to return to recommendations by the CDC and the Advisory Committee on Immunization Practices (ACIP) on using nirsevimab in young children. Infants and children recommended for nirsevimab should be immunized as quickly as possible. 

As of January 23, 2024, the CDC's RSVVaxView reported that among females with an infant <8 months, 28.7% said their infant received nirsevimab in 2023. Among females who are currently pregnant, 33.9% reported that they plan to get nirsevimab for their infant. Among females who are trying to get pregnant, 44.2% said that they plan to get nirsevimab for their infant.

Protein Chemical Formula: C6494H10060N1708O2050S46; Protein Average Weight: 146300.0 Da (approximate),  PubChem SID: 384585358.  ChEMBL: ChEMBL4297575. CPT codes: 96380, 96381

In March 2017, Sanofi and AstraZeneca announced an agreement to develop and commercialize Beyfortus and share all costs and profits. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY. AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company. BEYFORTUS - Trademark Details: 90557485

A research firm, GlobalData plc, issued a seven-year sales forecast on July 24, 2023, indicating Beyfortus is set to reach global sales of $1.27 billion in 2029. Beyfortus sales reached €410 million in the fourth quarter and €547 million in 2023. AstraZeneca announced on February 8, 2024, that Beyfortus' fourth quarter's revenues included $122m, including $41m of Alliance Revenue for AstraZeneca’s share of gross profits outside the US, $27m of Collaboration Revenue for a sales milestone and $54m of Product Sales from product supplied to Sanofi.

Beyfortus (Nirsevimab) Effectiveness

On January 25, 2023, the journal Eurosurveillance published a study that concluded Beyfortus was about 70% effective at preventing RSV hospitalizations in infants in Luxembourg. On December 28, 2023, The New England Journal of Medicine published results from an Original Article that included 8,058 infants in a phase 3 clinical trial. Eleven infants (0.3%) in the nirsevimab group and 60 (1.5%) in the standard care group were hospitalized for RSV-associated lower respiratory tract infection, which corresponded to a nirsevimab efficacy of 83.2% (95% confidence interval [CI], 67.8 to 92.0; P<0.001). Very severe RSV-associated lower respiratory tract infection occurred in 5 infants (0.1%) in the nirsevimab group and 19 (0.5%) in the standard care group, which represented a nirsevimab efficacy of 75.7% (95% CI, 32.8 to 92.9; P=0.004). 

Beyfortus (Nirsevimab) Preterm Infants

The Lancet published results from a study in February 2024 that concluded preterm infants accounted for about 25% of RSV hospitalization burden in a meta-analysis. Preventive products for RSV can have a substantial public health impact by preventing RSV-severe outcomes in preterm infants. In 2023, the phase 3 MELODY clinical trial assessed the efficacy of Beyfortus in infants born at a gestational age of at least 35 weeks. In term and late-preterm infants, a single dose of nirsevimab provided a consistent level of protection against hospitalization for RSV-associated lower respiratory tract infection and severe, medically attended RSV-associated lower respiratory tract infection during an RSV season.

Beyfortus (Nirsevimab) Availability 2024

Beyfortus is available in the U.S. for the 2023-2024 RSV season. As of December 14, 2023, Beyfortus manufacturers committed 1.4 million doses for delivery in the U.S. before February 2024, a 27% increase over the initial supply forecast. On December 14, 2023, it was announced that 230,000 additional doses of Beyfortus would become available in the U.S. in January 2024. This allocation follows 77,000 doses of Beyfortus released in November 2023Sanofi stated in October 2023 that demand for this product, especially for the 100 mg doses, had been higher than anticipated. On November 16, 2023, the CDC announced the release of Beyfortus to physicians and hospitals through the Federal VFC Program and commercial channels. On October 23, 2023, the CDC published a Health Alert Network Health Advisory to provide options for clinicians in the context of a limited supply of Beyfortus. As of October 2023, the CDC transitioned to an allocation-based system for distributing Beyforus to public health. See the American Academy of Pediatrics Ordering Vaccines webpage for additional guidance on ordering vaccines in the U.S.

Beyfortus was approved by the European Union (EMA EMEA/H/C/005304) in October 2022. Beyfortus was approved by the UK Medicines and Healthcare Products Regulatory Agency in November 2022 and Canada in 2023. Japan named Beyfortus a medicine for prioritized development under the Project for Drug Selection to Promote New Drug Development in Pediatrics by the Japan Agency for Medical Research and Development. GlobalData's RSV Forecast in Asia-Pacific (India, Urban China, Australia, South Korea, and Japan) Markets to 2028 reveals that Urban China will lead the Asia-Pacific market for RSV prevention in 2028, accounting for 34.8% of the overall market size and that Beyfortus may dominate this market.

Beyfortus (Nirsevimab) U.S. FDA

The U.S. FDA Approved Beyfortus in July 2023. The FDA's Antimicrobial Drugs Advisory Committee met on June 8, 2023, to discuss the Briefing Document and presentations (2) for the biologics license application (BLA) 761328 submitted by AstraZeneca AB for use with certain neonates, infants, and children. The Committee voted 21-0 in favor of approval. If approved by the FDA, nirsevimab could be available in the U.S. for the 2023/2024 RSV season. On February 5, 2019, the FDA granted Breakthrough Therapy Designation for MEDI8897, an extended half-life RSV F mAB developed to prevent LRTI caused by RSV. On January 5, 2022, AstraZeneca's BLA for nirsevimab was accepted for review by the U.S. FDA for the prevention of RSV LRTI in newborns and infants entering or during their first RSV season and for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. The BLA was based on results from the comprehensive nirsevimab clinical development program, including the MELODY Phase III, MEDLEY Phase II/III (first and second RSV season), and Phase IIb trials.

Beyfortus (Nirsevimab) U.S. CDC

The U.S. CDC recommends passive immunization to protect all infants under eight months and some older babies at increased risk of severe illness caused by RSV. The U.S. CDC Advisory Committee on Immunization Practices (ACIP) meeting on August 3, 2023, reviewed recommendations, updated nirsevimab EtRFeasibility/implementation plans for monitoring safety/effectiveness 2nd season, and Clinical considerations. The ACIP voted unanimously to include Beyfortus in the Vaccines for Children program and for use in all infants below eight months.

The ACIP previously met on June 22, 2023, and reviewed Clinical Considerations for RSVpreF maternal vaccine and nirsevimab, presented by Jefferson Jones, MD MPH FAAP. On February 23, 2023, the ACIP reviewed presentations: Introduction, Cost-effectiveness analysis for nirsevimab – CDC model; Cost-effectiveness analysis for nirsevimab – Comparison to manufacturer model; Evidence to Recommendations framework for nirsevimab; Clinical considerations for nirsevimab; Safety and Efficacy of RSV Bivalent PreF Maternal Vaccine; Workgroup considerations. On October 20, 2022, Dr. C Felter prevented Nirsevimab. Updated safety and efficacy of the ACIP. Previously, the CDC's ACIP meeting on June 23, 2022, reviewed - Nirsevimab For The Prevention of RSV Disease In All Infants.

Beyfortus (Nirsevimab) Indication

Nirsevimab is designed to be administered to infants born (below eight months of age) during the RSV season or children entering their first or second RSV season. In Canada, Beyfortus is also approved for use in infants up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. RSV is a common, contagious virus that causes seasonal epidemics of LRTI, leading to bronchiolitis and pneumonia in infants. According to the CDC, it is also a leading cause of hospitalizations in all infants.

Beyfortus (Nirsevimab) Dosage

Beyfortus is given as a single injection into the thigh muscle. The recommended dose is 50 mg for children weighing less than 5 kg and 100 mg for children weighing 5 kg or more.

Beyfortus (Nirsevimab) Mechanism of Action

Nirsevimab is a recombinant human immunoglobulin G1 kappa (IgG1ĸ) long-acting mAbs that binds to the prefusion conformation of the RSV F protein. RSV is coated with two types of glycoproteins: the attachment glycoprotein (G protein) and the fusion glycoprotein (F protein). Of these two, only the F protein is essential for entering the virus into cells lining the respiratory tract, making it a desirable drug target. The RSV F protein is initially in a metastable prefusion conformation and undergoes conformational changes after being triggered by an unknown event. These conformational changes lead to a postfusion conformation, where both viral and host-cell membranes are together. Nirsevimab binds to a highly conserved RSV prefusion F protein epitope, inhibiting the membrane fusion step in the viral entry process. This allows nirsevimab to neutralize various RSV A and B strains and block cell-to-cell fusion. Nirsevimab has also been modified with a triple amino acid substitution (M257Y/S259T/T261E [YTE]) in the Fc region to extend serum half-life from the typical 21–28 days to approximately 69 days.

Beyfortus (Nirsevimab) Price

As of October 5, 2023, the price for Beyfortus through the Vaccines for Children (VFC) program is $395.00 for 100mg and $395.00 for 50mg through March 31, 2024. The U.S. private-sector nirsevimab costs $495 per dose for 50mg and 100mg or $990 for 200mg doses (Two 100mg doses). As of August 3, 2023, Beyfortus was included in the CDC's VFC program in the U.S. On February 23, 2023, the U.S. CDC reviewed presentations: A cost-effectiveness analysis for nirsevimab – CDC model; Cost-effectiveness analysis for nirsevimab – Comparison to manufacturer model.

Beyfortus (Nirsevimab) CPT Codes

As of October 6, 2023, the AAP approved two new Current Procedural Terminology (CPT) codes related to the administration of nirsevimab, one of which accounts for the work associated with providing counseling: 96380 Administration of RSV, monoclonal antibody, seasonal dose by intramuscular injection, with counseling by physician or other qualified health care professional; 96381 Administration of RSV, monoclonal antibody, seasonal dose by intramuscular injection.

RSV Season 2023-2024

RSV season news is posted at Precision Vax.

Beyfortus (Nirsevimab) News

January 2, 2024 - Professor Liu Hanmin, President of West China Second University Hospital, Sichuan University, commented in a press release, "There is currently no specific treatment for RSV disease in infants.... This approval (Beyfortus) is crucial to preventing and controlling RSV disease in China." 

December 14, 2023 - The companies wrote - we plan to provide approximately 230,000 additional doses - made up of 50mg and 100mg doses - for the U.S. in January. This would bring the first season to an immunization rate of nearly 40 percent, which significantly surpasses prior launches of pediatric immunizations and represents a total of 1.4 million babies offered protection against RSV, a 27 percent increase over the initial supply forecast for the season.

August 3, 2023 - Thomas Triomphe, Executive Vice President of Vaccines, Sanofi, commented, "Today, we have turned the corner on the threat of RSV to our youngest, most vulnerable population. The ACIP's unanimous recommendations for routine use of Beyfortus and inclusion in the Vaccines for Children program are critical steps toward providing millions of parents in the U.S. with the ability to protect their babies through their first RSV season when they are most susceptible to severe RSV disease. We appreciate the FDA and CDC leadership and the ACIP public health experts for recognizing and quickly acting on the threat RSV poses to all infants."

May 12, 2023 - Thomas Triomphe, Executive Vice President, Vaccines, Sanofi, stated, "The HARMONIE data demonstrate the real-world impact  nirsevimab has on pediatric hospitalizations and illustrate its importance for infants, their families, and public health."

November 4, 2022 - AstraZeneca and Sanofi announced that the European Commission had approved Beyfortus in the EU to prevent RSV lower respiratory tract disease in newborns and infants during their first RSV season.

May 11, 2022 - AstraZeneca announced results from a prespecified pooled analysis of the pivotal MELODY Phase III and Phase IIb trials showed AstraZeneca and Sanofi's nirsevimab demonstrated an efficacy (relative risk reduction versus placebo) of 79.5% (95% Confidence Interval [CI] 65.9 to 87.7; P<0.0001) against medically attended lower respiratory tract infections (LRTI), such as bronchiolitis or pneumonia, caused by RSV in infants born at term or preterm entering their first RSV season.

March 3, 2022 - Sanofi announced the New England Journal of Medicine published detailed results from a Phase 3 trial evaluating nirsevimab involving healthy infants born at term or late preterm (35 weeks gestational age or more significant) entering their first RSV season and met the primary endpoint, reducing the incidence of medically attended lower respiratory tract infections, such as bronchiolitis or pneumonia, caused by RSV by 74.5% (95% CI 49.6 to 87.1; P<0.001) compared to placebo.

August 11, 2021 - A peer-reviewed study concluded: Based on the mechanism of action of the new generation of anti-viral mAbs, such as nirsevimab, which is highly specific in targeting viral antigenic sites, it is unlikely that it could interfere with the immune response to other vaccines.

March 3, 2017 - Sanofi Pasteur announced today an agreement with MedImmune, the global biologics research and development arm of AstraZeneca, to develop and commercialize a monoclonal antibody--called MEDI8897--for the prevention of RSV-associated illness in newborns and infants. 

Beyfortus (Nirsevimab) Clinical Trials

Nirsevimab has been tested in several clinical trials. The primary endpoint was met in both trials (prevention of MA RSV LRTI) – Trial 03 RRR 70.1%, 95% CI (52.3%, 81.2%) – Trial 04 Primary Cohort RRR 74.9%, 95% CI (50.6%, 87.3%).

The Hospitalized RSV Monoclonal Antibody Prevention (HARMONIE) phase 3b randomized open-label study of nirsevimab prevents hospitalizes-dosing to RSV in infants under 12 months. The visit frequency will be one in-person dosing/randomization visit, with monthly safety follow-up electronic contacts through the first six months post-dosing/randomization. The study will also include a 12-month (Day 366) final follow-up telephone call. The study duration will be 12 months postdosing/randomization. Last updated on November 30, 2022.

 In the MELODY and Phase 2b trials, Beyfortus postdose endpoint of reducing the incidence of medically attended lower respiratory tract infections (LRTI) caused by RSV during the RSV season vs. placebo with a single dose. The Phase IIb study was a randomized, placebo-controlled trial designed to measure the efficacy of Beyfortus against medically attended LRTI through 150 days postdose. Healthy preterm infants of 29–35 weeks' gestation were randomized (2:1) to receive a 50mg intramuscular injection of Beyfortus or a placebo. The dosing regimen was recommended based on further exploration of the Phase IIb data. In the subsequent Phase III study, MELODY applied the recommended dosing regimen.

The MELODY Phase III study was a randomized, placebo-controlled trial conducted across 21 countries designed to determine the efficacy of Beyfortus against medically attended LRTI due to RSV confirmed by reverse transcriptase polymerase chain reaction testing through 150 days after dosing versus placebo in healthy late preterm and term infants (35 weeks gestational age or more significant) entering their first RSV season.

MEDLEY was a Phase II/III, randomized, double-blind, Synagis-controlled trial to assess safety and tolerability for Beyfortus in preterm infants and infants with congenital heart disease and/or chronic lung disease of prematurity (CLD) eligible to receive Synpost-dose9 Between July 2019 and May 2021, approximately 918 infants entering their first RSV season were randomized to receive a single 50mg (in infants weighing <5kg) or 100mg (in infants weighing ≥5kg) intramuscular injection of Beyfortus or Synagis. Safety was assessed by monitoring the occurrence of TEAEs and TESAEs through 360 days postdose.1,8,9 Serum levels of Beyfortus following dosing (on day 151) in this trial were comparable with those observed in the MELODY Phase III trial, indicating similar protection in this population to that in the healthy term and late preterm infants are likely. Data was published in the New England Journal of Medicine in March 2022.

Clinical Trials