A monoclonal antibody stands out against omicron subvariants: a call to action for a wider access to bebtelovimab

Hentzien, Maxime; Autran, Brigitte; Piroth, Lionel; Yazdanpanah, Yazdan; Calmy, Alexandra

doi:10.1016/s1473-3099(22)00495-9

Cited by 40 publications

(39 citation statements)

References 3 publications

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“…Our study was also limited to BA.4 and BA.5, and we did not analyze the sensitivity of other Omicron subvariants, such as BA.2.75 53–55 . We did not have access to the medical formulation of Bebtelovimab 33 . Fc-effector functions are influenced by the method of antibody preparation, the isotype, Fc glycosylation and mutations.…”

Section: Discussionmentioning

confidence: 99%

“…It is recommended to inject a double-dose of Evusheld, as serum neutralization is decreased against BA.1 and BA.2 in individuals receiving these antibodies as PrEP [28][29][30][31] . Bebtelovimab is similarly effective against ancestral strains and Omicron BA.1 and BA.2 32 , but its access is so far restricted to the United States 33 . Thus, a continuous evaluation of mAbs efficacy against new variants is needed to optimize their utilization.…”

Section: Introductionmentioning

confidence: 99%

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Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 in patients receiving monoclonal antibodies

Bruel

Stéfic

Nguyen

et al. 2022

Preprint

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The emergence of novel Omicron lineages, such as BA.5, may impact the therapeutic efficacy of anti-SARS-CoV-2 neutralizing monoclonal antibodies (mAbs). Here, we evaluated the neutralization and ADCC activity of 6 therapeutic mAbs against Delta, BA.2, BA.4 and BA.5 isolates. The Omicron sub-variants escaped most of the antibodies but remained sensitive to Bebtelovimab and Cilgavimab. Consistent with their shared spike sequence, BA.4 and BA.5 displayed identical neutralization profiles. Sotrovimab was the most efficient at eliciting ADCC. We also analyzed 121 sera from 40 immunocompromised individuals up to 6 months after infusion of 1200 mg of Ronapreve (Imdevimab + Casirivimab), and 300 or 600 mg of Evusheld (Cilgavimab + Tixagevimab). Sera from Ronapreve-treated individuals did not neutralize Omicron subvariants. Evusheld-treated individuals neutralized BA.2 and BA.5, but titers were reduced by 41- and 130-fold, respectively, compared to Delta. A longitudinal evaluation of sera from Evusheld-treated patients revealed a slow decay of mAb levels and neutralization. The decline was more rapid against BA.5. Our data shed light on the antiviral activities of therapeutic mAbs and the duration of effectiveness of Evusheld pre-exposure prophylaxis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 in patients receiving monoclonal antibodies

Bruel

Stéfic

Nguyen

et al. 2022

Preprint

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“…After careful evaluation the panel decided not to evaluate drugs that are currently not available outside the United States (i.e. bebtelovimab) [ 3 ].…”

Section: Methodsmentioning

confidence: 99%

European society of clinical microbiology and infectious diseases guidelines for coronavirus disease 2019: an update on treatment of patients with mild/moderate disease

Bartoletti

Azap

Barać

et al. 2022

Clinical Microbiology and Infection

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“…17 Bebtelovimab is clinically effective 18 but its availability is currently limited to the United States. 19 The tixagevimab-cilgavimab combination retains a neutralizing activity against all of the Omicron sublineages – albeit at a lesser extent than that observed against prior variants. 17,20–22 While tixagevimab-cilgavimab has been originally developed for pre-exposure prophylaxis, 8 it represented the only efficient mAbs combination available in France during the Omicron wave.…”

mentioning

confidence: 97%

Tixagevimab-cilgavimab as an early treatment for COVID-19 in kidney transplant recipients

Benotmane

Olagne

Gautier-Vargas

et al. 2022

Preprint

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Objective: This single-center retrospective study evaluated the use of tixagevimab-cilgavimab as an early treatment for COVID-19 in kidney transplant recipients (KTRs) during the omicron wave. Methods: KTRs were deemed at high risk for moderate-to-severe COVID-19 in presence of at least one comorbidity (age >60 years, diabetes, obesity, or cardiovascular disease) associated with a weak humoral response (<264 BAU/mL). All other KTRs were considered at low risk. The two groups were stratified according to the administration of tixagevimab-cilgavimab and compared in terms of COVID-19-related hospitalization, oxygen need, ICU admission, and mortality. Results: Of the 61 KTRs at high risk, 26 received tixagevimab-cilgavimab. COVID-19-related hospitalizations (3.8% versus 34%, p=0.006) and oxygen need (3.8% versus 23%, p=0.04) were significantly less frequent in patients who received tixagevimab-cilgavimab. In addition, non-significant trends towards a lower number of ICU admissions (3.8% versus 14.3% p=0.17) and deaths (0 versus 3, p=0.13) were observed after administration of tixagevimab-cilgavimab. Ten of the 73 low-risk KTRs received tixagevimab-cilgavimab, and no significant clinical benefit was observed in this subgroup. Conclusion: Early administration of tixagevimab-cilgavimab may be clinically useful in high-risk KTRs with COVID-19; however, no major benefit was observed for low-risk patients.

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A monoclonal antibody stands out against omicron subvariants: a call to action for a wider access to bebtelovimab

Cited by 40 publications

References 3 publications

Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 in patients receiving monoclonal antibodies

Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 in patients receiving monoclonal antibodies

European society of clinical microbiology and infectious diseases guidelines for coronavirus disease 2019: an update on treatment of patients with mild/moderate disease

Tixagevimab-cilgavimab as an early treatment for COVID-19 in kidney transplant recipients

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