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Bebtelovimab (LY-CoV1404) Monoclonal Antibody

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September 27, 2022
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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. This anti-SARS-CoV-2 monoclonal antibody (mAb) is reported to maintain binding and neutralizing activity across reported coronavirus variants of concern (VOC), including Omicron and subvariants.

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.

An in-depth assessment of mutations that could inhibit the neutralization of Bebtelovimab identified two specific amino acid positions that are very rarely mutated in the general population (0.027%), as reported in the GISAID database April 2021. In addition, the potent activity of Bebtelovimab against the currently known variants of concern (VOC) and pseudoviruses carrying various single amino acid mutations suggests that Bebtelovimab binds to an epitope that is highly conserved across SARS-CoV-2 isolates that have been collected worldwide.

AbCellera (Nasdaq: ABCL) announced on May 4, 2021, that LY-CoV1404 had entered human clinical trials. AbCellera also released preclinical data showing LY-CoV1404 binds to a rarely mutated region of the SARS-CoV-2 spike protein and neutralizes VOCs. In addition, on Jan. 9, 2022, AbCellera confirmed that bebtelovimab maintains both full and potent neutralization activity against the original Omicron variant.

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. Under the EUA, fact sheets that provide essential information about using bebtelovimab to treat COVID-19 as authorized must be made available to healthcare providers, patients, and caregivers. The fact sheets include dosing instructions, drug interactions, and potential side effects. The EUA was issued to Eli Lilly and Co.

The U.S. NIH issued an updated COVID-19 Treatment Guidelines Panel on the Role of Bebtelovimab for the Treatment of High-Risk, Nonhospitalized Patients With Mild to Moderate COVID-19' on August 8, 2022. And on June 15, 2022, the CDC published: Interim Clinical Considerations for COVID-19 Treatment in Outpatients.

The peer-review journal The Lancet Infectious Diseases published a CORRESPONDENCE on September 26, 2022 - Bebtelovimab: considerations for global access to treatments during a rapidly evolving pandemic. This modified regulatory approach which met the US requirements for emergency use during a health emergency, or regulatory mutual recognition, could serve as a global model to accelerate authorization of next-generation vaccines and therapeutics within the current and future pandemics to help patients worldwide.

On September 7, 2022, the U.S. HHS's Assistant Secretary for Preparedness and Response (ASPR) confirmed that (19,500) doses of Bebtelovimab would be distributed to states, territories, and agencies this week. HHS has 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. At the current rate of use, the additional doses purchased for this initiative are expected to be available through September 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. In addition, a revised Fact Sheet for Providers (EUA Revised Date: 05/20/22) and Emergency Use Authorization Letter 111 were published.

Bebtelovimab Price

 Bebtelovimab's list price is $2,100 per dose, 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. In North Carolina, the health department urges people to know their rights when it comes to COVID-19 treatments, which are available regardless of insurance or immigration status.

Additional antibody price and discount information is posted at InstantRx™.

Bebtelovimab Availability

Eli Lilly and Co confirmed on August 3, 2022, that it plans to make Bebtelovimab commercially available to U.S. states, as well as hospitals and other healthcare providers beginning August 15, 2022. 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.

Bebtelovimab Dosage

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 as soon as possible 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 BA.x Sublineages

As of September 2022, the U.S. NIH OpenData Portal reported Bebtelovimab's positive in vitro therapeutic activity against coronavirus variants. On July 15, 2022, a non-peer-reviewed study generated pseudoviruses harboring the spike proteins of BA.2.75, BA.4/5, and BA.2 and evaluated the efficacy of ten therapeutic monoclonal antibodies and three antibody cocktails against BA.2.75. The journal Nature published a peer-reviewed study on July 5, 2022, that found among therapeutic antibodies authorized for clinical use, only bebtelovimab retains full potency against both BA.2.12.1 and BA.4/5. The Company confirmed on June 29, 2022, that Bebtelovimab continues to maintain neutralization activity against the Omicron variants (BA.2.12.1 and BA.4/BA.5) in addition to all known variants of interest and concern.

In addition, the AMA stated on May 24, 2022, 'Bebtelovimab has demonstrated in vitro effectiveness against BA.2 variants. On May 17, 2022, Lilly representatives indicated Bebtelovimab was effective against new Omicron BA.2 variants. The peer-review journal Cell Reports described LY-CoV1404 (bebtelovimab) on Apr. 25, 2022, with a broad spectrum of activity across all current variants (BA.2 subvariant), and the Binding epitope on RBD of SARS-CoV-2 is rarely mutated based on current GISAID data.

On March 25, 2022, the U.S. HHS/ASPR stated that bebtelovimab is a monoclonal antibody therapy, and based on current vitro assay data, this mAbs product is likely to retain activity against the BA.2 variant. And a study published by the peer-reviewed journal Nature on March 3, 2022, LY-CoV1404 (bebtelovimab) was the only authorized mAbs therapy adequately covering all sublineages of the Omicron variant.

Bebtelovimad For Women

Severe hypersensitivity reactions 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 birth defects, 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 that are 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%). Serious hypersensitivity reactions, including anaphylaxis, have been observed with the administration of 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 treatment 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.

Bebtelovimab Revenues

On August 4, 2022, the Company confirmed 2Q2022 COVID-19 antibodies sales for bamlanivimab administered alone, for bamlanivimab and etesevimab
administered together, and for bebtelovimab, 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.

Eli Lilly & Co. confirmed on February 10, 2022, that the pending agreement with the U.S. government's estimated financial impact in 2022 is at least $720 million of revenue and approximately $0.20 of EPS. Previously, the Company recognized U.S. revenue from COVID-19 antibodies of $1.029 billion in the fourth quarter of 2021 compared to $850 million in the fourth quarter of 2020. Excluding COVID-19 antibodies, Lilly's revenue in the U.S. increased by 11%.

AbCellera (Nasdaq: ABCL) reported royalties associated with bamlanivimab and bebtelovimab were $307.0 million in Q1 2021. 

Bebtelovimab News

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.

Clinical Trials

No clinical trials found