Inmazeb (atoltivimab/maftivimab/odesivimab-ebgn) / Regeneron - LARVOL DELTA

Impact of most promising Ebola therapies on survival: a secondary analysis during the tenth outbreak in the Democratic Republic of Congo. (PubMed, Virol J) - "Prompt identification and treatment, along with enhanced supportive care (such as replenishing fluids and electrolytes and managing symptoms), significantly improve survival chances. Concurrently, administering vaccines and using mAb114, REGN-EB3, and, to some extent, Remdesivir further increase patient survival rates."

Journal • Retrospective data • Ebola Virus Disease • Infectious Disease

Remdesivir, mAb114, REGN-EB3, and ZMapp partially rescue nonhuman primates infected with a low passage Kikwit variant of Ebola virus. (PubMed, Nat Commun) - "A trend of more escape mutants in the GP1 and GP2 domains was observed for the mAb114 group. Our data show similar suboptimal efficacy of individual therapeutics in the uniformly lethal NHP model of EVD, supporting further clinical investigation of therapeutic combinations to maximize the overall therapeutic effect and improve patient outcomes, particularly for the treatment of advanced stage EVD."

Journal • Ebola Virus Disease • Infectious Disease

EBO-PEP: EBOla Post-Exposure Prophylaxis (clinicaltrials.gov) - P3 | N=160 | Not yet recruiting | Sponsor: ANRS, Emerging Infectious Diseases

New P3 trial • Ebola Virus Disease • Infectious Disease

Recent advances in the treatment of Ebola disease: A brief overview. (PubMed, PLoS Pathog) - "Additionally, multiple vaccines have been approved for EBOD prevention by various regulatory bodies, with Ervebo, a recombinant vesicular stomatitis virus-vectored vaccine against EBOV being the first vaccine to receive approval by the FDA in 2019. This review covers the key signs and symptoms of EBOD, its modes of transmission, and the principles guiding supportive care. Furthermore, it explores recent advancements in treating and preventing EBOD, highlighting the unique properties of each therapeutic agent and the ongoing progress in discovering new treatments."

Journal • Ebola Virus Disease • Infectious Disease

Case fatality risk among individuals vaccinated with rVSVΔG-ZEBOV-GP: a retrospective cohort analysis of patients with confirmed Ebola virus disease in the Democratic Republic of the Congo. (PubMed, Lancet Infect Dis) - "To our knowledge, this is the first observational study describing the protective effect of rVSVΔG-ZEBOV-GP vaccination against death among patients with confirmed Ebola virus disease admitted to an Ebola health facility. Vaccination was protective against death for all patients, even when adjusted for Ebola virus disease-specific treatment, age group, and time from symptom onset to admission."

Journal • Retrospective data • Ebola Virus Disease • Infectious Disease

Effect of anti-Ebola virus monoclonal antibodies on endogenous antibody production in survivors of Ebola virus disease in the Democratic Republic of the Congo: an observational cohort study. (PubMed, Lancet Infect Dis) - P=N/A | "Almost a quarter of survivors were seronegative on discharge from the Ebola treatment centre and antibody concentrations decreased rapidly over time. These results indicate that monoclonal antibodies might negatively affect the production of anti-Ebola virus antibodies in survivors of Ebola virus disease which could increase the risk of reinfection or reactivation."

Journal • Observational data • Ebola Virus Disease • Human Immunodeficiency Virus • Infectious Disease

"In any case, the voucher came free with Inmazeb (their Ebola mAb cocktail)" (@tastlevin)

Ebola Virus Disease • Infectious Disease

Ebola virus disease: A review for the emergency medicine clinician. (PubMed, Am J Emerg Med) - "EVD is a potentially deadly condition that can present with a wide range of signs and symptoms. Emergency clinicians must be aware of the presentation, evaluation, and management to optimize the care of these patients."

Journal • Review • Hematological Disorders • Infectious Disease • Musculoskeletal Pain • Pain

Structure of the Inmazeb cocktail and resistance to Ebola virus escape. (PubMed, Cell Host Microbe) - "This structure allows the modeling of previously disordered portions of the glycoprotein glycan cap, maps the non-overlapping epitopes of Inmazeb, and illuminates the basis for complementary activities and residues critical for resistance to escape by these and other clinically relevant antibodies. We further provide direct evidence that Inmazeb protects against the rapid emergence of escape mutants, whereas monotherapies even against conserved epitopes do not, supporting the benefit of a cocktail versus a monotherapy approach."

Journal • Infectious Disease

AAV-monoclonal antibody expression protects mice from Ebola virus without impeding the endogenous antibody response to heterologous challenge. (PubMed, Mol Ther Methods Clin Dev) - "Vectorized expression of murine IgG2a or human IgG1 mAbs led to sustained expression in the serum of mice for >400 days or for the lifetime of the animal, respectively. AAV6.2FF-mediated mAb expression offers an alternative to recombinant antibody administration in scenarios where long-term protection is preferable to passive immunization."

Journal • Preclinical • Hematological Disorders • Infectious Disease

A Drug-Disease Model for Predicting Survival in an Ebola Outbreak. (PubMed, Clin Transl Sci) - "The model also predicted survival in clinical trials with appropriate scaling to humans. This mathematical investigation demonstrates that drug-disease modelling can be an important translational tool to integrate preclinical data from a NHP model recapitulating disease progression to guide future translation of preclinical data to clinical study design."

Journal • Hematological Disorders • Infectious Disease

Effects of therapies for Ebola virus disease: a systematic review and network meta-analysis. (PubMed, Lancet Microbe) - "REGN-EB3 and mAb114 separately reduce mortality compared with ZMapp, remdesivir, or standard care in patients with Ebola virus disease. These findings suggest that health-care workers should prioritise the use of REGN-EB3 and mAb114 for patients with Ebola virus disease during future outbreaks."

Journal • Retrospective data • Review • Infectious Disease

Structural Biology Illuminates Molecular Determinants of Broad Ebolavirus Neutralization by Human Antibodies for Pan-Ebolavirus Therapeutic Development. (PubMed, Front Immunol) - "Next, we highlight key structural studies that have advanced our understanding of ebolavirus glycoprotein structures and mechanisms of antibody-mediated neutralization. Finally, we offer examples of how structural biology has contributed to advances in anti-viral medicines and discuss what opportunities the future holds, including rationally designed next-generation therapeutics with increased potency, breadth, and specificity against ebolaviruses."

Journal • Review • Hematological Disorders • Infectious Disease

A systematic review of Ebola virus disease outbreaks and an analysis of the efficacy and safety of newer drugs approved for the treatment of Ebola virus disease by the US Food and Drug Administration from 2016 to 2020. (PubMed, J Infect Public Health) - "Overall, Inmazeb is the preferred drug of choice over ZMapp or other drugs for the treatment of EVD, and Ebanga is a choice in patients with cardiovascular complications. In addition to that, supportive care is very essential to control the mortality rate."

FDA event • Journal • Review • Cardiovascular • Hypotension • Infectious Disease

Pilot Study Evaluating the Impact of Delay Between Administration of Inmazeb Administration and Vaccination by Ervebo on Vaccine Immune Response on Healthy Volunteers (clinicaltrials.gov) - P2a; N=135; Not yet recruiting; Sponsor: ANRS, Emerging Infectious Diseases

Clinical • New P2a trial • Infectious Disease

Identification and Characterization of a Novel Single Domain Antibody Against Ebola Virus. (PubMed, Virol Sin) - "Interestingly, we found that the binding of M24 to GP at pH 5.5 has dramatically decreased compared to the binding at pH 7.5, which may lead to weak efficacy in the neutralization of authentic EBOV. Since no sdAb against EBOV infection has been reported to date, our results not only give a proof of concept that sdAbs could be utilized for the development of potential therapeutic candidates against EBOV infection, but also provide useful information for the discovery and improvement of anti-EBOV agents."

Journal • Hematological Disorders • Infectious Disease

Post-exposure prophylaxis following high-risk contact with Ebola virus, using immunotherapies with monoclonal antibodies, in the eastern DRC: an emergency use program. (PubMed, Int J Infect Dis) - "14 days after the contact, all contacts were free of symptoms and all had negative RT-PCR Immunotherapies appears to be promising candidates to protect contacts of Ebola Virus Disease. Interaction with vaccine and larger study on efficacy need to be conducted."

Journal • Infectious Disease

A computational overview on phylogenetic characterization, pathogenic mutations, and drug targets for Ebola virus disease. (PubMed, Curr Opin Pharmacol) - "The current US FDA-approved anti-EVD vaccine, ERVERBO, and the other equally effective anti-EBOV combinations of three fully human monoclonal antibodies such as REGN-EB3, primarily target the envelope glycoprotein. This work elaborates on the EBOV's phylogenetic structure and the crucial mutations associated with viral pathogenicity."

Journal • Review • Infectious Disease

Review: Insights on Current FDA-Approved Monoclonal Antibodies Against Ebola Virus Infection. (PubMed, Front Immunol) - "More recently, during the second-largest Ebola outbreak in North Kivu and Ituri provinces, Democratic Republic of the Congo (DRC), four IPs, including one small molecule (Remdesivir), two monoclonal antibody (mAb) cocktails (ZMapp and REGN-EB3) and a single mAb (mAb114), were evaluated in an RCT, the Pamoja Tulinde Maisha (PALM) study...The interaction between FDA-approved mAbs and vaccines remains unclear and needs to be investigated. In this review, we summarize the efficacy and safety results of the PALM study and review current research questions for the further development of mAbs in pre-exposure or emergency post-exposure use."

FDA event • Journal • Review • Infectious Disease

Investigational Therapeutics for the Treatment of People With Ebola Virus Disease (clinicaltrials.gov) - P2/3; N=681; Completed; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); N=1044 ➔ 681

Clinical • Enrollment change • Infectious Disease

Therapeutics development for Ebola virus disease: A recent scenario. (PubMed, Curr Opin Pharmacol) - "Presently, two monoclonal antibodies (REGN-EB3 and mAb114) showed better efficacy in the Pamoja tuLinde Maisha trial and received approval from the United States Food and Drug Administration. However, scientists should focus on developing more economic therapeutics."

Journal • Review • Infectious Disease

Atoltivimab/maftivimab/odesivimab (Inmazeb) combination to treat infection caused by Zaire ebolavirus. (PubMed, Drugs Today (Barc)) - "Additionally, Inmazeb has displayed significant reduction in mortality in the PALM (PAmoja tuLinde Maisha) trial, when compared with the control arm receiving ZMapp. Inmazeb has received orphan drug designation from both the U.S. FDA and the European Medicines Agency (EMA)."

Journal • Infectious Disease • Pediatrics • PCR

Proteo-Genomic Analysis Identifies Two Major Sites of Vulnerability on Ebolavirus Glycoprotein for Neutralizing Antibodies in Convalescent Human Plasma. (PubMed, Front Immunol) - "The largest Ebola virus disease (EVD) epidemic to date in 2013-2016 in West Africa highlighted the urgent need for countermeasures, leading to the development and FDA approval of the Ebola virus vaccine rVSV-ZEBOV (Ervebo) in 2020 and two monoclonal antibody (mAb)-based therapeutics (Inmazeb [atoltivimab, maftivimab, and odesivimab-ebgn] and Ebanga (ansuvimab-zykl) in 2020. Polyclonal plasma antibodies from the survivor reacted broadly to EBOV, BDBV, and SUDV GP, while reactivity of the potently neutralizing mAbs we identified was limited mostly to the homologous EBOV GP. Together these results reveal a restricted diversity of neutralizing humoral response in which mAbs targeting two antigenic sites on GP - glycan cap and base - play a principal role in plasma-antibody-mediated protective immunity against EVD."

Journal • Infectious Disease

Commentary Title: COVID-19 Research, Africa, and Global Health. (PubMed, J Virus Erad) - No abstract available

Clinical • Journal • Dental Disorders • Human Immunodeficiency Virus • Immunology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Tuberculosis

"Any remaining doses of REGN-EB3 or ansuvimab in the DRC?" (@noblerzen)