Bebtelovimab Monoclonal Antibody
Eli Lilly and Company Bebtelovimab (LY-CoV1404, LY3853113) is a neutralizing IgG1 monoclonal antibody (mAb) directed against the spike protein of the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD)-specific antibody identified from a convalescent patient sample. Bebtelovimab (LY-CoV1404) is highly potent, which could have implications for reducing the number of antibodies necessary for clinical dosing, and potentially enabling a subcutaneous route of administration for either treatment or prevention of COVID-19. Pathway: SARS-CoV-2 spike glycoprotein [KO: K24152], ko03230; Viral genome structure, ko05171 COVID-19.
This anti-SARS-CoV-2 monoclonal antibody is reported to maintain binding and neutralizing activity across reported betacoronavirus variants of concern (VOC), including Omicron and subvariants. On February 11, 2022, U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for bebtelovimab for the treatment of mild to moderate COVID-19 in certain people 12 years of age and older weighing at least 40 kilograms, with a positive COVID-19 test, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by the FDA are not accessible or clinically appropriate. The EUA was issued to Eli Lilly and Co.
On November 30, 2022, the U.S. FDA announced that Bebtelovimab was no longer authorized for emergency use in the U.S. because it is not expected to neutralize Omicron subvariants BQ.1 and BQ.1.1. Additionally, the European Medicines Agency (EMA) continues evaluating mAbs in 2023.
Eli Lilly and Company (NYSE: LLY), Based in Indianapolis, Indiana, was founded in 1876 and continues to monitor the COVID-19 pandemic and its global impact closely. Company-based disclosures are published at https://www.covid19.lilly.com/bebtelovimab/hcp.
Bebtelovimab's list price was $2,100 per dose in 2022, according to Eli Lilly. During the EUA, the U.S. government pays for the product and service. The Medicare payment rate for administering COVID-19 monoclonal antibody products authorized or approved by the FDA is approximately $350.50. Additional antibody price and discount information is posted at InstantRx™.
Eli Lilly and its authorized distributors paused the commercial distribution (AmerisourceBergen) of bebtelovimab on November 30, 2022, until further notice by the FDA. Additionally, the Administration for Strategic Preparedness and Response has paused fulfilling any pending requests under its Bebtelovimab Product Replacement Initiative. Retained products must be appropriately held in accordance with storage conditions detailed in the authorized Fact Sheet for Health Care Providers and the Letter of Authorization for bebtelovimab.
On September 7, 2022, the U.S. HHS's Assistant Secretary for Preparedness and Response (ASPR) confirmed that it had distributed (726,056) Bebtelovimab doses in the USA since February 14, 2022. And on September 23, 2022, HHS confirmed it is making 60,000 doses of bebtelovimab to treat qualifying uninsured or underinsured patients for free by HHS. In addition, on June 29, 2022, Eli Lilly and Company announced a modified purchase agreement with the U.S. government to supply an additional 150,000 doses of bebtelovimab for approximately $275 million.
Provider Fact Sheet as of March 25, 2022: DOSAGE AND ADMINISTRATION: The dosage in adults (18 years and older) and pediatric patients (≥12 years of age and weighing at least 40 kg) is bebtelovimab 175 mg administered as a single intravenous injection over at least 30 seconds. Administer bebtelovimab immediately after positive results of direct SARS-CoV-2 viral testing and within seven days of symptom onset. No contraindications have been identified based on the limited available data for the emergency use of bebtelovimab.
Bebtelovimab Omicron Sublineages
Nowcast data from the U.S. CDC published in November 2022 estimates that the combined proportion of COVID-19 cases caused by the Omicron BQ.1 and BQ.1.1 subvariants is above 57% nationally. Therefore, given that a COVID-19 infection is likely to be caused by a non-susceptible SARS-CoV-2 variant and consistent with the terms and conditions of the Letter of Authorization, bebtelovimab is not currently authorized for emergency use in any U.S. region at this time.
Bebtelovimad For Women
Severe hypersensitivity and infusion-related reactions have been observed with the administration of bebtelovimab, including in pregnant women. There are insufficient data to evaluate a drug-associated risk of major congenital disabilities, miscarriage, or adverse maternal or fetal outcomes. Bebtelovimab should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus.
There are no available data on the presence of bebtelovimab in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Breastfeeding women with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.
Bebtelovimab Drug Interactions
Bebtelovimab is not renally excreted or metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are renally excreted or substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely. Thus, no contraindications have been identified based on the limited available data for the emergency use of bebtelovimab authorized under this EUA.
Bebtelovimab Side Effects
Possible side effects of bebtelovimab include itching, rash, infusion-related reactions, nausea, and vomiting. Serious and unexpected adverse events, including hypersensitivity, anaphylaxis, and infusion-related reactions, have been observed with other SARS-CoV2 monoclonal antibodies and could occur with bebtelovimab. Most common adverse reactions are infusion-related reactions (0.3%), pruritus (0.3%), and rash (0.8%). In addition, serious hypersensitivity reactions, including anaphylaxis, have been observed with other SARS-CoV-2 monoclonal antibodies and could occur with the administration of bebtelovimab. In addition, clinical worsening following administration of other SARS-CoV-2 monoclonal antibody treatments has been reported and therefore is possible with bebtelovimab. However, it is unknown if these events were related to SARS-CoV-2 monoclonal antibody use or were due to the progression of COVID-19.
Bebtelovimab Shelf Life
On May 20, 2022, the FDA and HHS/ASPR announced the authorization of an extension to the shelf-life from 12 months to 18 months for specific lots of the refrigerated Eli Lilly monoclonal antibody bebtelovimab.
On August 4, 2022, the Company confirmed 2Q2022 COVID-19 antibodies sales for bamlanivimab administered alone, bamlanivimab and etesevimab
administered together, and for bebtelovimab, it was $129.1.
Eli Lilly disclosed on June 29, 2022, that the 2022 estimated financial impact of the new agreement with the U.S. Government is approximately $275 million of revenue and approximately $0.08 of EPS.
AbCellera (Nasdaq: ABCL) reported royalties associated with bamlanivimab and bebtelovimab were $307.0 million in Q1 2021.
January 12, 2023 - The EMA continues its rolling review of mAbs.
November 30, 2022 - The U.S. FDA revoked its authorization for Bebtelovimab.
November 4, 2022 - U.S. FDA updates the fact sheet for Bebtelovimab.
September 17, 2022 - A peer-reviewed study: Comparable Outcomes for Bebtelovimab and Ritonavir-Boosted Nirmatrelvir Treatment in High-Risk Patients With Coronavirus Disease-2019 During Severe Acute Respiratory Syndrome Coronavirus 2 BA.2 Omicron Epoch, reported data showed that rates of severe disease did not differ significantly between the bebtelovimab (1.4%; 95% CI, 1.2%-1.7%) and Paxlovid (1.2%; 95% CI, 0.8%-1.5%) groups. Our findings support the emergency use authorization of bebtelovimab for the treatment of COVID-19 during the Omicron epoch dominated by BA.2 and subvariants.
August 4, 2022 - NEJM published a CORRESPONDENCE: Efficacy of Antibodies and Antiviral Drugs against Omicron BA.2.12.1, BA.4, and BA.5 Subvariants. 'Only bebtelovimab efficiently neutralized BA.2.12.1, BA.4, and BA.5; the FRNT50 values for these isolates were similar to those for the ancestral strain.'
August 3, 2022 - A report by The Wall Street Journal indicated that bebtelovimab would become commercially after August 15, 2022.
July 20, 2022 - A CORRESPONDENCE published by th peer-review journal the NEJM: Efficacy of Antibodies and Antiviral Drugs against Omicron BA.2.12.1, BA.4, and BA.5 Subvariants - Of the FDA-approved mAbs tested, only LYCoV1404 (bebtelovimab) efficiently neutralized BA.2.12.1, BA.4, and BA.5; the FRNT50 values for these isolates were similar to those for the ancestral strain.
July 18, 2022 - The Lancet Infectious Diseases published a Correspondance: Among all available monoclonal antibodies, bebtelovimab is the only one that has shown remarkably preserved in vitro activity against all SARS-CoV-2 variants, including the omicron variant and the most recent BA.4 and BA.5 subvariants that are now becoming dominant. Bebtelovimab should be evaluated against current predominant variants in clinical independent research, alone or in combination with other antiviral options, and should be used for clinical care when no other therapeutic options exist, especially in immunocompromised populations.
June 29, 2022 - "Lilly and its collaborators have partnered closely with the federal government throughout the pandemic to ensure broad and equitable access to our mAbs," said David A. Ricks, Lilly's chair and CEO. "While Congress works toward additional COVID-19 funding, Lilly and the U.S. government will continue to work together to support the availability of bebtelovimab to maximize equity and accessibility in the U.S. market."
June 15, 2022 - The U.S. CDC confirmed its Interim Clinical Considerations include 'When Paxlovid or remdesivir are not accessible or clinically appropriate, the monoclonal antibody bebtelovimab can be used.'
May 20, 2022 - The U.S. FDA and HHS/ASPR announced the authorization of an extension to the shelf-life from 12 months to 18 months for specific lots of the refrigerated bebtelovimab.
May 18, 2022 - Eli Lilly reported that internal testing has confirmed that bebtelovimab is effective against BA.2 and BA2.12.1 variants.
May 11, 2022 - Wiley Online Library published: Understanding Omicron: Transmissibility, immune evasion, and antiviral intervention.
May 2, 2022 - The Wisconsin Department of Health Services confirmed Bebtelovimab availability.
April 8, 2022 - The NASDAQ published an article: The fate of antibody treatments for COVID-19 looks uncertain, with the FDA recently revoking the previously granted Emergency Use Authorization given their lack of efficacy against the predominant Omicron variant in the U.S.
April 8, 2022 - The U.S. NIH confirmed therapeutic options are available to treat nonhospitalized adults with mild to moderate COVID-19 who are at high risk of disease progression.
March 25, 2022 - The U.S. FDA published an updated Provider Fact Sheet for Bebtelovimab.
March 24, 2022 - The State of Washington confirmed antibody and other COVID-19 treatments are effective and available.
March 11, 2022 - The LA Times reported that anti-COVID drugs given intravenously are not part of the "test to treat" pharmacy program.
March 2, 2022 - The U.S. NIH updated its treatment guidelines for bebtelovimab.
February 23, 2022 - The journal Nature published an article: Will a rising Omicron variant scramble antibody treatments?
February 11, 2022 - The U.S. FDA announced it had issued a EUA for Bebtelovimab applicable to specific people over the age of twelve. Bebtelovimab is not authorized for patients hospitalized due to COVID-19 or requiring oxygen therapy due to COVID-19. Treatment with bebtelovimab has not been studied in patients hospitalized due to COVID-19. The issuance of a EUA is different than an FDA Approval.
February 3, 2022 - Eli Lilly reported the Company submitted a request to the U.S. FDA for a EUA for bebtelovimab to treat mild-to-moderate COVID-19 in adults and pediatric patients 12 years old of age and older. Authentic virus analysis of bebtelovimab confirms earlier pseudovirus findings, demonstrating that Lilly's investigational antibody neutralizes concern variants, including Omicron.
January 9, 2022 - AbCellera and its collaborators released new preclinical data showing the pseudovirus neutralization status of its two monoclonal antibodies, bamlanivimab and bebtelovimab (LY-CoV1404), against the Omicron variant. In addition, the data confirmed that the investigational antibody bebtelovimabs, currently in Phase 2 clinical trials with Eli Lilly and Company, maintains full and potent neutralization activity against the Omicron variant and all other known SARS-CoV-2 variants of concern.
January 7, 2022 - The U.S. NIH published 'the breadth of reactivity to amino acid substitutions present among current VOC together with broad and potent neutralizing activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known virus variants causing COVID-19.'
January 5, 2022 - The journal Nature published a Letter: SARS-CoV-2 Omicron RBD shows weaker binding affinity than the currently dominant Delta variant to human ACE2. In conclusion, MD simulation and ELISA bioassay results suggest that the Omicron variant possesses comparable binding affinity to human ACE2 than the wild-type SARS-CoV-2 but much weaker binding affinity than the Delta variant. Accordingly, the Omicron variant might have similar infection capability to the WT virus but milder than Delta if the capability depends mainly on the binding affinity. In addition, the MD simulations indicate that the new variant Omicron has a high risk of immune evasion. Accordingly, close attention should be paid intensively to Omicron as its high immune evasion risk may enable its easy transmission.
September 9, 2021 - The U.S. NIH highlighted a non-peer-reviewed study: LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants. The RBD positions comprising the LY-CoV1404 epitope are highly conserved, except for N439 and N501; notably, the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y).
May 4, 2021 - AbCellera today announced that a second antibody from its collaboration with Eli Lilly and Company, LY-CoV1404, has entered clinical trials in patients with mild-to-moderate COVID-19. Lilly has expanded its ongoing BLAZE-4 trials to evaluate LY-CoV1404 alone and together with other monoclonal antibodies.
Bebtelovimab Clinical Trials
A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Mono and Combination Therapy With Monoclonal Antibodies in Participants With Mild to Moderate COVID-19 Illness (BLAZE-4).
AbCellera released preclinical data showing LY-CoV1404 binds to a rarely mutated region of the SARS-CoV-2 spike protein and neutralizes all currently known variants of concern.