XAV-19 a Glyco-Humanized polyclonal antibody targeting SARS-CoV-2 accelerates the recovery of mild to moderate COVID-19 patients and keeps its neutralizing activity against Omicron and its subvariants
Garyfallia Poulakou, Pierre-Joseph Royer, Nikolai Evgeniev, Gwénaëlle Evanno, Françoise Shneiker, Bernard Vanhove, Odile Duvaux, Stéphane Marot, Vincent Calvez
doi:10.1101/2023.10.09.23296726
Background: XAV-19 is a glyco-humanized swine polyclonal antibody targeting SARS-CoV-2. The safety and clinical efficacy of XAV-19 was investigated in patients with a WHO score of 2 to 4 in the WHO 7-point ordinal scale. The activity of XAV-19 against Omicron and its subvariants was assessed in vitro. Methods: A phase II/III, multicentric randomized double-blind placebo-controlled, clinical trial was conducted to evaluate the safety and clinical efficacy of XAV-19 in inpatients with COVID-19 requiring or not oxygen therapy and outpatients not requiring oxygen (EUROXAV trial, NCT04928430). Most patients were not vaccinated. The primary endpoint was the proportion of patients with an aggravation of COVID-19 within 8 days after treatment. Binding and neutralization of Omicron or its subvariants by XAV-19 was investigated by ELISA or with a whole virus neutralization assay. Results: Patients received either 150mg of XAV-19 (N=139) or placebo (N=140). Low enrolment forced the premature trial termination. XAV-19 was well tolerated. No difference in the primary endpoint, nor in the proportion with an improvement at day 8 (secondary endpoint) was observed between the 2 groups. For patients not requiring oxygen therapy, XAV-19 reduced the time to improvement significantly (7 days vs 14 days p=0.0159). Neutralizing activity against Omicron and BA.2, BA2.12.1, BA.4/5 and BQ1.1 subvariants was shown in vitro. Conclusions: XAV-19 did not reduce the aggravation in COVID-19 patients. While it did not bring any benefit to patients requiring oxygen, it reduced the time to improvement for patients not requiring oxygen (WHO score 2 or 3). These preliminary clinical data might indicate a therapeutic potential for patients with mild to moderate COVID-19 requiring supplementation with anti-SARS-CoV-2 neutralizing antibodies. .
References
Brady, Gurijala, Huang, Hussain, Lingan et al., A guide to <scp>COVID</scp> -19 antiviral therapeutics: a summary and perspective of the antiviral weapons against <scp>SARS-CoV</scp> -2 infection, FEBS J,
doi:10.1111/febs.16662Callaway, Hastie, Schendel, Li, Yu et al., Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium, Cell Rep,
doi:10.1016/j.celrep.2023.112014Cao, Wang, Wen, Liu, Wang et al., A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19, New England Journal of Medicine,
doi:10.1056/nejmoa2001282Casadevall, Focosi, SARS-CoV-2 variants resistant to monoclonal antibodies in immunocompromised patients constitute a public health concern, Journal of Clinical Investigation,
doi:10.1172/JCI168603Cunha, Stolet, Strauch, Pereira, Dumard et al., Polyclonal F(ab')2 fragments of equine antibodies raised against the spike protein neutralize SARS-CoV-2 variants with high potency, iScience,
doi:10.1016/j.isci.2021.103315Dhar, Sasmal, Varki, From "Serum Sickness" to "Xenosialitis": Past, Present, and Future Significance of the Nonhuman Sialic Acid Neu5Gc, Front Immunol,
doi:10.3389/fimmu.2019.00807Dong, Zost, Greaney, Starr, Dingens et al., Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail, Nat Microbiol,
doi:10.1038/s41564-021-00972-2Focosi, Maggi, Franchini, Mcconnell, Casadevall, Analysis of immune escape variants from antibody-based therapeutics against covid-19: A systematic review, Int J Mol Sci,
doi:10.3390/ijms23010029Gaborit, Dailly, Vanhove, Josien, Lacombe et al., Pharmacokinetics and Safety of XAV-19, a Swine Glyco-humanized Polyclonal Anti-SARS-CoV-2 Antibody, for COVID-19-Related Moderate Pneumonia: a Randomized, Double-Blind, Placebo-Controlled, Phase IIa Study, Antimicrob Agents Chemother,
doi:10.1128/AAC.01237-21Gupta, Gonzalez-Rojas, Juarez, Casal, Moya et al., Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19, JAMA,
doi:10.1001/jama.2022.2832Gupta, Konnova, Smet, Berkell, Savoldi et al., Host immunological responses facilitate development of SARS-CoV-2 mutations in patients receiving monoclonal antibody treatments, Journal of Clinical Investigation,
doi:10.1172/JCI166032Huang, Mccreary, Bariola, Minnier, Wadas et al., Effectiveness of Casirivimab-Imdevimab and Sotrovimab During a SARS-CoV-2 Delta Variant Surge, JAMA Netw Open,
doi:10.1001/jamanetworkopen.2022.20957Huo, Dijokaite-Guraliuc, Liu, Zhou, Ginn et al., A delicate balance between antibody evasion and ACE2 affinity for Omicron BA, Cell Rep,
doi:10.1016/j.celrep.2022.111903Kumari, Lu, Li, Huang, Hsu et al., A critical overview of current progress for COVID-19: development of vaccines, antiviral drugs, and therapeutic antibodies, J Biomed Sci,
doi:10.1186/s12929-022-00852-9Lopardo, Belloso, Nannini, Colonna, Sanguineti et al., RBD-specific polyclonal F(ab´)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial, EClinicalMedicine,
doi:10.1016/j.eclinm.2021.100843Nyberg, Ferguson, Nash, Webster, Flaxman et al., Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study, The Lancet,
doi:10.1016/S0140-6736(22)00462-7O'brien, Forleo-Neto, Sarkar, Isa, Hou et al., Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial, JAMA,
doi:10.1001/jama.2021.24939Planas, Bruel, Staropoli, Guivel-Benhassine, Porrot et al., Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies, Nat Commun,
doi:10.1038/s41467-023-36561-6Taiwo, Chew, Moser, Wohl, Daar et al., Phase 2 safety and antiviral activity of SAB-185, a novel polyclonal antibody therapy for nonhospitalized adults with COVID-19, J Infect Dis,
doi:10.1093/infdis/jiad013Turtle, Thorpe, Drake, Swets, Palmieri et al., Outcome of COVID-19 in hospitalised immunocompromised patients: An analysis of the WHO ISARIC CCP-UK prospective cohort study, PLoS Med,
doi:10.1371/journal.pmed.1004086Vanhove, Duvaux, Rousse, Royer, Evanno et al., High neutralizing potency of swine glyco-humanized polyclonal antibodies against SARS-CoV-2, Eur J Immunol,
doi:10.1002/eji.202049072Vanhove, Marot, So, Gaborit, Evanno et al., XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants, Front Immunol,
doi:10.3389/fimmu.2021.761250Vanhove, Marot, So, Gaborit, Evanno et al., XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants, Front Immunol,
doi:10.3389/fimmu.2021.761250Widyasari, Kim, A Review of the Currently Available Antibody Therapy for the Treatment of Coronavirus Disease 2019 (COVID-19), Antibodies,
doi:10.3390/antib12010005DOI record:
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"abstract": "<jats:p>Background: XAV-19 is a glyco-humanized swine polyclonal antibody targeting SARS-CoV-2. The safety and clinical efficacy of XAV-19 was investigated in patients with a WHO score of 2 to 4 in the WHO 7-point ordinal scale. The activity of XAV-19 against Omicron and its subvariants was assessed in vitro. Methods: A phase II/III, multicentric randomized double-blind placebo-controlled, clinical trial was conducted to evaluate the safety and clinical efficacy of XAV-19 in inpatients with COVID-19 requiring or not oxygen therapy and outpatients not requiring oxygen (EUROXAV trial,<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04928430\">NCT04928430</jats:ext-link>). Most patients were not vaccinated. The primary endpoint was the proportion of patients with an aggravation of COVID-19 within 8 days after treatment. Binding and neutralization of Omicron or its subvariants by XAV-19 was investigated by ELISA or with a whole virus neutralization assay. Results: Patients received either 150mg of XAV-19 (N=139) or placebo (N=140). Low enrolment forced the premature trial termination. XAV-19 was well tolerated. No difference in the primary endpoint, nor in the proportion with an improvement at day 8 (secondary endpoint) was observed between the 2 groups. For patients not requiring oxygen therapy, XAV-19 reduced the time to improvement significantly (7 days vs 14 days p=0.0159). Neutralizing activity against Omicron and BA.2, BA2.12.1, BA.4/5 and BQ1.1 subvariants was shown in vitro. Conclusions: XAV-19 did not reduce the aggravation in COVID-19 patients. While it did not bring any benefit to patients requiring oxygen, it reduced the time to improvement for patients not requiring oxygen (WHO score 2 or 3). These preliminary clinical data might indicate a therapeutic potential for patients with mild to moderate COVID-19 requiring supplementation with anti-SARS-CoV-2 neutralizing antibodies.</jats:p>",
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