Beyfortus™ (Nirsevimab) RSV Monoclonal Antibody Clinical Trials, Dosage, Efficacy, Side Effects
Beyfortus™ (Nirsevimab-alip) (MEDI8897) is the first Approved single-dose, extended half-life monoclonal antibody (mAb) offering passive immunization to prevent lower respiratory tract infections (LRTI) caused by the respiratory syncytial virus (RSV) to newborns and infants experiencing their first or second RSV season and those with congenital heart disease or chronic lung disease. Beyfortus binds to the prefusion conformation of the RSV fusion protein and was developed in partnership between AstraZeneca and Sanofi using AstraZeneca's YTE technology. In clinical trials, Beyfortus was about 90% (95% CI = 75%–96%) protective against RSV-associated hospitalization in infants in their first RSV season. As of June 28, 2024, observational data indicate that Beyfortis (nirsevimab) was working as expected (vs. RCT results).
The concept of using passive immunization strategies to prevent severe RSV illness during infancy is not new. The first proof of principle results came from studies performed during the mid-1980s using animal models of RSV infection. Palivizumab, a humanized RSV-F mouse monoclonal IgG subclass 1, was first approved by the U.S. Food and Drug Administration (FDA) in 1998.
Beyfortus was approved by the European Union (EU) on November 4, 2022. On July 17, 2023, the FDA Approved Beyfortus. As of May 2024, RSVVaxView reported that among females with an infant <8 months in the United States, 43% reported that their infant received nirsevimab. As of July 2024, Beyfortus was recommended in Australia, Canada, China, Europe (EMEA/H/C/005304), Japan, and France. On July 25, 2024, the Ontario Ministry of Health announced a universal public program with Beyfortus for all newborns and infants born in 2024 and through the 2024-2025 RSV season. This also includes some high-risk children up to 24 months old.
On September 11, 2024, a study published by the American Academy of Pediatrics (AAP) concluded that Beyfortus (Nirsevimab) could effectively protect a broad infant population against RSV infection: 63.1% reduction in acute bronchiolitis-related hospital admissions (95% confidence interval [CI], 60.9% to 65.2%), and a 63.1% reduction in pediatric intensive care unit admissions (95% CI, 58.1% to 67.9%). As of September 28, 2024, the AAP recommends Beyfortus for all infants (not otherwise protected through vaccination during pregnancy). On November 14, 2024, the CDC reported that in Alaska, nirsevimab was 89% effective in preventing RSV-associated hospitalization for infants in their first RSV season and 76% and 88% effective against medically attended illness for children in their first and second seasons, respectively.
The World Health Organization (WHO) published preferred product characteristics of monoclonal antibodies for passive immunization against RSV disease. In September 2024, the WHO SAGE recommended that all countries introduce passive immunization to prevent severe RSV disease in young infants.
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.
Beyfortus Sales 2024
Sanofi announced on October 25, 2204, that during Q3, 15.7% sales growth was boosted by earlier-than-anticipated vaccine sales. Beyfortus sales were €645 million, driven by early deliveries in the U.S. and rollout in about 20 countries in 2024. Beyfortus sales were limited to €18 million (USD 19.6) in the second quarter of 2024.
Beyfortus (Nirsevimab) Effectiveness
In October 2024, The Lancet published a study (Volume 8, Issue 10) estimating Beyfortus's effectiveness against RSV-associated hospitalizations for bronchiolitis at 73% (61–84), corresponding to one hospitalization averted for every 39 (26–54) doses administered. On July 10, 2024, the New England Journal of Medicine reported that in a real-world setting, Beyfortus reduced the risk of infant hospitalization for RSV- associated bronchiolitis by 83%. The effectiveness of therapy against RSV-associated bronchiolitis resulting in critical care was 69.6% (95% CI, 42.9 to 83.8) (27 of 193 case-patients [14.0%] vs. 47 of 146 matched control patients [32.2%]) and against RSV-associated bronchiolitis resulting in ventilatory support was 67.2% (95% CI, 38.6 to 82.5) (27 of 189 case-patients [14.3%] vs. 46 of 151 matched control patients [30.5%]).
On June 28, 2024, the U.S. CDC vaccine committee reviewed presentations that confirmed Beyfortus' effectiveness. On June 5, 2024, the journal Influenza and Other Respiratory Diseases published a Short Communication that estimated nirsevimab effectiveness at 75.9% (48.5–88.7) in the primary analysis and 80.6% (61.6–90.3) and 80.4% (61.7–89.9) in two sensitivity analyses. During that 2023-2024 RSV season in the U.S., Beyfortus reduced RSV hospitalizations by 82% (95% CI: 65.6 to 90.2) in infants under six months of age, compared to infants who received no RSV intervention, according to the interim results of an ongoing study published in The Lancet on April 30, 2024. On April 4, 2024, a study from Spain published in Vaccines found Beyfortus's effectiveness was 88.7% in preventing hospitalizations among infants immunized at birth, compared to no intervention. On March 7, 2024, the U.S. CDC announced that in phase 3 clinical trials, nirsevimab's efficacy against RSV-associated lower respiratory tract infection with hospitalization was 81% (95% CI = 62%–90%) through 150 days after receipt. Among 699 infants hospitalized with acute respiratory illness, 59 (8%) received nirsevimab ≥7 days before symptom onset.
Beyfortus (Nirsevimab) Availability 2024
Beyfortus was available in the U.S. for the 2023-2024 RSV season, and 50mg and 100mg Injection doses will be available for the 2024-2025 RSV season. Supply is secured for 20 countries in 2024. Sanofi also launched the BEYFORTUS Reservation Program, which provides critical insight into private healthcare provider demand and allows for prioritized fulfillment of requests placed through the program.
As of May 2024, among females with an infant <8 months, 41.3% reported to the CDC that their infant received nirsevimab. Among 42 state and city IIS jurisdictions, nirsevimab geographic coverage among infants <8 months ranged from 2.4% to 22.8%. Among eight U.S. territorial and affiliated island jurisdictions, coverage ranged from 0.0% to 14.9%. The companies confirmed on May 2, 2024, that the expansion of the Beyfortus manufacturing network is progressing according to plan, empowering Sanofi and AstraZeneca to more than triple manufacturing capacity. On November 16, 2023, the CDC announced the release of Beyfortus to physicians and hospitals through the Federal VFC Program and commercial channels. Ordering Vaccines webpage contains additional guidance on ordering vaccines in the U.S.
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.
Beyfortus (Nirsevimab) U.S. CDC
As of July 2024, the U.S. Centers for Disease Control and Prevention (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 CDC Advisory Committee on Immunization Practices (ACIP) meeting on June 28, 2024, reviewed various presentations. On August 3, 2023, the ACIP reviewed recommendations, updated nirsevimab EtR, Feasibility/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 CDC Morbidity and Mortality Weekly Report confirmed in March 2024 that Beyfortus's effectiveness was about 90% against RSV-associated hospitalization in infants in their first RSV season. On January 4, 2024, the CDC advised healthcare providers to return to recommendations (CDCHAN-00499) 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.
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 ACIP meeting on June 23, 2022, reviewed - Nirsevimab For The Prevention of RSV Disease In All Infants.
Beyfortus (Nirsevimab) Indication
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. 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. Beyfortus is approved for use in infants 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. 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. 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. In Canada, Quebec's National Institute of Excellence in Health and Social Services recommends BEYFORTUS® to be used to prevent RSV LRTD in all neonates and infants aged eight months and younger.
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) 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.
Beyfortus Drug Safety-related Labeling Changes
Serious hypersensitivity reactions have been reported (02/23/2024, SUPPL-7) following BEYFORTUS administration. These reactions included urticaria, dyspnea, cyanosis, and/or hypotonia. Anaphylaxis has been observed with human immunoglobulin G1 monoclonal antibodies. If signs and symptoms of anaphylaxis or other clinically significant hypersensitivity reactions occur, initiate appropriate treatment.
Beyfortus Adverse Reactions Postmarketing Experience
Adverse reactions have been identified during the post-approval use of BEYFORTUS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Sanofi SP0125
The phase 3 clinical study evaluating the Sanofi SP0125 (VAD00001) live attenuated vaccine for preventing RSV in toddlers will be active in 2024. SP0125 is administered through the nasal route.
RSV Season
RSV season news is posted at Precision Vax.
Beyfortus (Nirsevimab) Price
As of 2024, 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 Business News
Beyfortus sales reached €200 million in the first quarter of 2024, €410 million in the fourth quarter, and €547 million in 2023. On July 25, 2024, Thomas Triomphe, Sanofi’s EVP of vaccines, informed analysts, “We’re confident that Beyfortus will be a blockbuster in 2024,” 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. GlobalData's RSV Forecast reveals that 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) News
July 25, 2024 - The Honourable Sylvia Jones, Ontario Deputy Premier and Minister of Health, commented, "Our government is taking steps to ensure Ontarians of all ages have the tools they need to be prepared and keep their loved ones safe and healthy ahead of respiratory virus season. Our government is working with our partners to significantly expand Ontario's RSV program, to make it easier for families to connect to the care they need, improving health outcomes and reducing the number of hospitalizations and ICU admissions resulting from RSV."
June 28, 2024 - The U.S. CDC vaccine committee reviewed various data presented by Amanda Payne, PhD, MPH, that support the continued use of Beyfortus for most infants during the 2024-2025 RSV season.
April 18, 2024—Delphine Lansac, General Manager of Vaccines Canada at Sanofi, said in a press release, "Parents and physicians who experience the impacts of RSV annually have been waiting for a preventative option that can cover the entire infant population and protect our most vulnerable.
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, 23—Thomas Triomphe, Executive Vice president of vaccines atines at 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 concludes that, Based on the mechanism of action of the new generation of antiviral 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, 17—Sanofi Pasteur announced today an agreement with MedImmune, the global biologics research and development arm of AstraZeneca, to develop and commercialize MEDI8897, a monoclonal antibody 897, 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 (prevention of MA RSV was met in both trials: TI)—Trial 03 RRR 70.1%, 95% CI (52.3%, 8, and 2%)—Trial 04 Primary Cohort RRR 74.9%, 95% CI (50.6%, 87.3%).
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.
In the MELODY and Phase 2b trials, the Beyfortus postdose endpoint was to reduce 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.
