MEDI8852 / AstraZeneca - LARVOL DELTA

Monoclonal antibodies against influenza viruses: a clinical trials review. (PubMed, Front Immunol) - "MHAA4549A demonstrated a 97.5% reduction in viral load in H3N2 models and showed synergistic effects with oseltamivir in severe cases. However, despite preclinical promise, others, such as VIR-2482 (intramuscular) and MEDI8852, failed in Phase 2 trials...mAbs hold promise for high-risk groups and pandemics but require further engineering to enhance efficacy and overcome biological barriers. Refinements in administration and design could establish monoclonal antibodies (mAbs) as a key tool in the management of influenza."

Journal • Review • Gastrointestinal Disorder • Infectious Disease • Influenza • Pain • Respiratory Diseases

Polyclonal and Monoclonal Antibodies for the Treatment and Prevention of Influenza. (PubMed, J Infect Dis) - "The COVID-19 pandemic demonstrated that these approaches, especially monoclonal antibodies, may have unique potential in certain stages of disease and populations, especially in preventing severe disease in a population without preexisting immunity or in those with a limited capacity to mount an effective humoral immune response. This review summarizes past and ongoing efforts in using monoclonal and polyclonal antibodies for the treatment and prevention of influenza, focusing on products that have entered clinical trials and drawing lessons from COVID-19 to direct future efforts on these strategies."

Journal • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

A monoclonal anti-hemagglutinin stem antibody modified with zanamivir protects against both influenza A and B viruses. (PubMed, Proc Natl Acad Sci U S A) - "The MEDI8852-zanamivir conjugate extends the circulatory half-life of zanamivir, targets both influenza HA and NA, and shows enhanced antibody-dependent cellular cytotoxicity (ADCC) compared to MEDI8852 alone. The MEDI8852-zanamivir conjugate protected mice from a lethal (10 × LD50) challenge with influenza A and B viruses at a dose similar to that required for broadly neutralizing anti-NA antibodies, with the added advantage of simultaneously targeting NA (influenza A and B) and HA (influenza A)."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Computational design and improvement of a broad influenza virus HA stem targeting antibody. (PubMed, Structure) - "This approach was applied to optimize MEDI8852, a nAb targeting the stalk region of influenza A virus hemagglutinin (HA)...Computational modeling reveals that this improvement can be attributed to the fine-tuning of interactions between the antibody's side-chains and the epitope residues that are highly conserved across the influenza A virus HA stalk. Our dry-wet iterative protocol for nAb optimization presented here yielded a promising candidate for influenza intervention."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Pre-exposure antibody prophylaxis protects macaques from severe influenza. (PubMed, Science) - "Macaques receiving MEDI8852 at 10 milligrams per kilogram or higher had negligible impairment of respiratory function after infection, whereas control animals were not protected from severe disease and fatality. Given the breadth of MEDI8852 and other bnAbs, we anticipate that protection from unforeseen pandemic influenza A viruses is achievable."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Anti-idiotype isolation of a broad and potent influenza A virus-neutralizing human antibody. (PubMed, Front Immunol) - "Surprisingly, the chemistries of L5A7 interactions with hemagglutinin and with anti-idiotype were substantially different. Overall, we demonstrate anti-idiotype-based isolation of a broad and potent influenza A virus-neutralizing antibody, revealing that anti-idiotypic selection of antibodies can involve features other than chemical mimicry of the target antigen."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Sequence-Signature Optimization Enables Improved Identification of Human HV6-1-Derived Class Antibodies That Neutralize Diverse Influenza A Viruses. (PubMed, Front Immunol) - "Threading indicated the refined signature to have increased accuracy, and signature-identified heavy chains, when paired with the light chain of MEDI8852, showed neutralization comparable to the most potent members of the class. Incorporating sequences of additional class members thus enables an improved sequence signature for HV6-1-class antibodies, which can identify class members with increased accuracy."

Journal • Infectious Disease • Respiratory Diseases

Survival during influenza-associated bacterial superinfection improves following viral- and bacterial-specific monoclonal antibody treatment. (PubMed, JCI Insight) - "FY1 and an optimized version, MEDI8852, anti-influenza HA mAbs, have been shown to neutralize influenza virus during singular influenza infection. We also observed improved survival when mice were treated with a combination of FY1 and MEDI4893* late during the course of postinfluenza MRSA pneumonia. In conclusion, both FY1 and MEDI4893* prolong survival when used in a murine model of postinfluenza MRSA pneumonia, suggesting pathogen-specific mAbs as a possible therapeutic in the context of bacterial superinfection."

Journal • Immunology • Infectious Disease • Pneumonia • Respiratory Diseases

Evaluation of the Safety and Efficacy of a Monoclonal Antibody to Treat Influenza (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: MedImmune LLC; N=68 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal

Evaluation of MEDI8852, an Anti-Influenza A Monoclonal Antibody, in Treating Acute Uncomplicated Influenza. (PubMed, Antimicrob Agents Chemother) - P2a; "Genotypic analyses found a limited number of hemagglutinin and neuraminidase amino acid changes between viruses isolated before and after therapy; however, none appeared within a known oseltamivir-resistant site or MEDI8852-binding region. The safety profile of MEDI8852 supports its continued development for treatment of patients hospitalized with influenza A infection."

Journal

Evaluation of the Safety and Efficacy of a Monoclonal Antibody to Treat Influenza (clinicaltrials.gov) - P2; N=68; Not yet recruiting; Sponsor: MedImmune LLC; Trial completion date: Oct 2019 ➔ Oct 2020; Initiation date: Apr 2019 ➔ Apr 2020; Trial primary completion date: Oct 2019 ➔ Oct 2020

Clinical • Trial completion date • Trial initiation date • Trial primary completion date

Evaluation of the Safety and Efficacy of a Monoclonal Antibody to Treat Influenza (clinicaltrials.gov) - P2; N=68; Not yet recruiting; Sponsor: MedImmune LLC

Clinical • New P2 trial