Beyfortus® (Nirsevimab) RSV Monoclonal Antibody March 2023
Beyfortus® (Nirsevimab) (MEDI8897) was developed in partnership between AstraZeneca and Sanofi using AstraZeneca's YTE technology. Beyfortus is the first extended half-life monoclonal antibody (mAb) that originated as a passive immunization to prevent lower respiratory tract infections (LRTI) caused by the respiratory syncytial virus (RSV). Nirsevimab binds to the prefusion conformation of the RSV fusion protein. It is designed to protect infants experiencing their first RSV season and infants with congenital heart disease or chronic lung disease entering their first and second RSV season. In addition, on. Beyfortus provides direct prophylactic protection via an antibody to help prevent LRTI caused by RSV.
In June 2021, the World Health Organization (WHO) published preferred product characteristics (June 2022) for mAbs for passive immunization against RSV disease in infants and considerations for global use.
The peer-review New England Journal of Medicine published a 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.
Beyfortus was approved in the European Union (EU) on November 4, 2022, to prevent RSV lower respiratory tract disease in newborns and infants during their first RSV season. The EU approval was based on results from the Beyfortus 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 UK's Medicines and Healthcare Products Regulatory Agency approved nirsevimab on November 9, 2022.
Beyfortus® (Nirsevimab) has also been granted regulatory designations to facilitate expedited development by several regulatory agencies, including Breakthrough Therapy Designation by The China Center for Drug Evaluation under the National Medical Products Administration; access granted to the European Medicines Agency PRIority MEdicines scheme; Promising Innovative Medicine designation by the U.K. Medicines and Healthcare products Regulatory Agency, and named "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.
The JAMA Network published an Orginal Investigation on February 17, 2023, suggesting nirsevimab is associated with substantial benefits in preventing RSV infection in children. Compared with placebo, with moderate- to high-certainty evidence, nirsevimab was associated with significantly reduced RSV-related infections per 1000 participants (nirsevimab: −123 [95% CI, −138 to −100].
And The Lancet Infectious Diseases, published on March 17, 2023, a company-sponsored analysis of observational study sequencing data that concluded nirsevimab binding site was highly conserved between 1956 and 2021. And nirsevimab escape variants were rare and have not increased over time.
In March 2017, Sanofi and AstraZeneca announced an agreement to develop and commercialize nirsevimab 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. PubChem SID: 384585358. ChEMBL: ChEMBL4297575
Beyfortus (Nirsevimab) U.S. FDA
On January 5, 2022, AstraZeneca's Biologics License Application (BLA) for nirsevimab was accepted for review by the U.S. Food and Drug Administration (FDA) for the prevention of RSV lower respiratory tract disease 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 (primary cohort and all subjects), MEDLEY Phase II/III (first and second RSV season), and Phase IIb trials. The FDA's target action date for its decision, Prescription Drug User Fee Act date, is in the third quarter of 2023. If approved, then nirsevimab will 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 monoclonal antibody (mAb) being developed to prevent LRTI caused by RSV.
Beyfortus (Nirsevimab) Cost Effectiveness
On February 23, 2023, the U.S. Centers for Disease Control and Prevention (CDC) reviewed presentations: A cost-effectiveness analysis for nirsevimab – CDC model; Cost-effectiveness analysis for nirsevimab – Comparison to manufacturer model.
A separate Canadian study focused on another RSV mAbs concluded on February 1, 2023: Cost-effectiveness results of PVZ as an RSV prophylaxis were heterogeneous across studies. Palivizumab may be considered cost-effective in specific subgroups: infants with bronchopulmonary dysplasia / chronic lung disease, infants with congenital heart disease, term infants from specific remote communities with high baseline RSVH rates, and preterm infants with and without lung complications.
Beyfortus (Nirsevimab) U.S. CDC
The U.S. CDC Advisory Committee on Immunization Practices (ACIP) meeting on February 23, 2023, 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 to 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 from birth to infants born during the RSV season or at the season's start for infants entering their first RSV season. RSV is a common, contagious virus that causes seasonal epidemics of LRTI, leading to bronchiolitis and pneumonia in infants. It is also a leading cause of hospitalizations in all infants.
AstraZeneca is working with the global clinical community to advance the understanding of RSV and is partnering with the ReSViNET Foundation to create the first global RSV surveillance dashboard set to launch in March 2023. Since February 2018, The ReSViNET Foundation has been officially registered as a not-for-profit entity under Dutch law.
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) News 2023
February 21, 2023 - Iskra Reic, Executive Vice President, Vaccines and Immune Therapies, AstraZeneca, said: "We believe that Beyfortus has the potential to transform the medical community's approach to preventing RSV infections in infants, and this is of particular importance given the recent surges of the virus amongst infants this past winter season."
January 5, 2023 - Iskra Reic, EVP, Vaccines and Immune Therapies, AstraZeneca, said in a press release, "This (FDA) decision brings us a step closer to delivering a first-in-class preventative option for a broad infant population in the US. If approved, we believe nirsevimab may transform the medical community's approach to RSV prevention in infants. We are committed to working with the FDA to support the completion of the review as quickly as possible."
November 11, 2022 - The Harmonie phase 3 study intends to recruit more than 20,000 infants in the UK, Germany, and France.
November 9, 2022 - The MHRA approved Beyfortus® (nirsevimab) to prevent RSV lower respiratory tract disease in newborns and infants during their first RSV season.
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.
September 16, 2022 - Jean-François Toussaint, Global Head of Research and Development Vaccines, Sanofi, stated: "Today's positive CHMP opinion is one of the most significant public health achievements in RSV in decades and has the potential to alleviate the enormous physical and emotional burden that RSV can place on families and healthcare systems. With this endorsement, we are one step closer to achieving our goal of protecting all infants against RSV with a single dose."
August 12, 2022 - Sanofi and the National Institute for Health and Care Research announced that the first patient had been enrolled in the Hospitalised RSV Monoclonal Antibody Prevention (HARMONIE) study, an open-label trial that will evaluate the use of nirsevimab, a passive immunization, in a broad population.
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 greater) 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. Taken together, we anticipate that nirsevimab could be concomitantly administered to infants with routine pediatric vaccines during the same clinic visit.
June 28, 2021 - Sanofi announced Nirsevimab shows positive topline results in RSV Phase 2/3 MEDLEY trial.
July 30, 2020 - Sanofi published detailed results from the Phase 2b trial for nirsevimab showing a significant reduction in medically attended lower respiratory tract infections (LRTI), mainly bronchiolitis and pneumonia hospitalizations caused by the respiratory syncytial virus (RSV) in healthy preterm infants.
February 5, 2019 - AstraZeneca and its global biologics research and development arm, MedImmune, announced that the U.S. FDA granted Breakthrough Therapy Designation for MEDI8897.
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 Hospitalized RSV Monoclonal Antibody Prevention (HARMONIE) phase 3b randomized open-label study of nirsevimab prevents hospitalizpost-dosingto 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 post-dosing/randomization. Last updated on November 30, 2022.
In the MELODY and Phase 2b trials, Beyfortus mpost-doserimary 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 single 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 post-dose.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.
