Bamlanivimab (formerly known as LY CoV 555, LY 3819253) is a neutralising human IgG1 monoclonal antibody directed against the spike protein of SARS-CoV-2, being developed by Eli Lilly and AbCellera for the treatment and prevention of COVID-2019 infections. Bamlanivimab has been developed using AbCellera's pandemic response platform, which is a microfluidic platform that uses miniaturised assays to screen antibodies from individual B cells from any species, including directly from human patients. Bamlanivimab neutralises the virus and potentially prevents and treats COVID-2019 by blocking the viral attachment and entry into human cells. It is also capable of neutralising the N439K variant. Bamlanivimab is approved both as monotherapy and combination therapy in Italy under emergency use authorisation for COVID-2019 infections. Candidate is also approved under emergency pathway as a monotherapy in Czech Republic, Germany, Israel, Sweden, Panama, Kuwait and UAE and also authorised for emergency use in Rwanda and Morocco in collaboration with Bill & Melinda Gates Foundation. Late stage clinical development is underway in multiple countries.

In February 2021, the bamlanivimab and etesevimab combination received emergency use authorisation (EUA) for the treatment of COVID-2019 infections in the US, however as of May 2022, due to high frequency of circulating SARS-CoV-2 variants in the US that are non-susceptible to bamlanivimab and etesevimab, the US FDA has unauthorized its use ^[1] . In November 2020, bamlanivimab was approved by US FDA under EUA for the treatment of mild to moderate COVID-19 infections, however in April 2021, the US FDA revoked the EUA based on the scientific data which showed sustained increase of SARS-CoV-2 viral variants that were resistant to bamlanivimab monotherapy ^[2] .Bamlanivimab in combination with etesevimab was under regulatory review in the EU in February 2021 for the treatment of COVID-2019 infections, However later the company withdrew the application ^[3] .

Bamlanivimab has advanced from a research programme for coronavirus neutralising antibodies by Eli Lilly and AbCellera [See Adis Insight drug profile 800057369].

In May 2022, GlaxoSmithKline changed its name to GSK ^[4] .

In July 2024, Abcellera expanded collaboration with Lilly to discover therapeutic antibodies for programs in immunology, cardiovascular disease, and neuroscience. In March 2020, Abcellera and Eli Lilly entered into a research and development agreement to develop antibodies for up to nine Eli Lilly-selected therapeutic targets. One of therapeutic targets is for treatment and prevention of COVID-19 infections, caused by SARS-CoV-2 coronavirus. Eli Lilly will select up to eight additional targets during the multi-year agreement. Abcellera's rapid pandemic response platform developed under the DARPA Pandemic Prevention Platform (P3) programme will be used in this collaboration along with Eli lilly's rapid development, manufacturing and distribution of therapeutic antibodies. Under the terms of agreement Abcellera and Eli lilly will together fund the initial development cost of the product, after which Eli lilly will be responsible for all further development, manufacturing and distribution. Eli lilly has paid AbCellera an up-front payment and will pay preclinical, clinical, and commercial milestones and tiered royalties on future sales. ^{[5] [6] [7]}

In January 2021, Eli Lilly, Vir Biotechnology and GlaxoSmithKline (now GSK) entered an agreement to evaluate bamlanivimab in combination with VIR 7831 for mild to moderate COVID-2019 infections. Eli Lilly will expand its ongoing BLAZE-4 trial to evaluate the efficacy of combined therapy. ^{[8] [4]}

In November 2021, AbCellera announced an additional purchase by the US government from Eli Lilly and Company for bamlanivimab with etesevimab for administration together. As part of the agreement, Lilly will supply 614 000 doses of bamlanivimab with etesevimab no later than January 31, 2022. A minimum of 400 000 doses will be supplied no later than December 31, 2021. The Lilly's agreement to provide the US government with 614 000 additional doses of bamlanivimab with etesevimab is for a sum of total of $US1.29 billion. In September 2021, Eli Lilly announced an additional purchase by the US government for its neutralizing antibody therapies authorized for emergency use as a treatment for COVID-19. As part of the agreement, Lilly will supply 388,000 doses of etesevimab to complement doses of bamlanivimab previously purchased by the US government, with approximately 200,000 doses expected to ship in Q3 2021 and the remaining to be shipped in Q4. This transaction is expected to generate approximately $US330 million in revenue in the second half of 2021. Earlier, in April 2021, Eli Lilly and the US government have agreed to modify the purchase agreement of bamlanivimab alone and focus on supply of bamlanivimab and etesevimab together. Additionally, the bamlanivimab and etesevimab agreement has been modified to enable the supply of etesevimab to complement doses of bamlanivimab the U.S. government already purchased, some of which have already been delivered to sites of care. This terminates the purchase agreement for bamlanivimab alone and cancels the remaining 350,856 doses that were scheduled to be delivered by the end of March 2021. Lilly's bamlanivimab received emergency use authorisation from the US FDA. Lilly subsequently developed bamlanivimab and etesevimab for administration together, in order to meet the potential challenge of SARS-CoV-2 variants likely to resist treatment with either monoclonal antibody used alone. Earlier, as of December 2020, Eli Lilly and Company has entered to a supply agreement with the US government, to supply multiple doses of Eli Lilly's bamlanivimab 700 mg for the treatment of COVID-2019 infections. The agreement is for $US812.5 million and the doses will be delivered through January 2021. In December 2020, The U.S. government has purchased 650 000 additional drug doses, the totaling to 950 000 doses of bamlanivimab. Additional 350 000 doses will delivered later in the same month. ^{[9] [10] [11] [12] [13]}

In September 2021, Eli Lilly and Company entered into a Joint Procurement Agreement with European Commission to supply up to 220,000 doses of bamlanivimab along with etesevimab to treat confirmed COVID-2019 infections in patients of age 12 years and above not requiring supplemental oxygen for COVID-2019 and who are at increased risk of progressing to severe infection. The agreement will help to provide access to treatments by enabling participating countries in the European Union (EU) and the European Economic Area (EEA) to purchase the drugs directly from Eli Lilly following national approval for emergency use or marketing authorization at the EU level. ^[14]

In April 2021, Eli Lilly and Company reported that the purchase agreement with the U.S. government for bamlanivimab alone was terminated, and orders were cancelled for the remaining 350,856 doses that were scheduled to be delivered by the end of March 2021. In February 2021, Junshi Biosciences and Eli Lilly and Company announced that the US Government agreed to purchase a minimum of 100,000 doses of etesevimab (JS016 or LY-CoV016) 1400 mg [see Adis Insight Drug profile800058525] and bamlanivimab (LY-CoV555) 700 mg [see Adis Insight Drug profile800058899] together. Additionally, the National Institutes of Health (NIH) recently updated the COVID-19 Treatment Guidelines to recommend the use of bamlanivimab plus etesevimab for the treatment of outpatients with mild to moderate COVID-19 who are at high risk of clinical progression. The agreement is for $210 million and 450,000 doses will be delivered through March 31, 2021. The U.S. government will have the option to purchase up to an additional 1,100,000 doses through November 25, 2021, under the same terms as the base agreement and subject to agreement from Lilly, product availability and the medical need in the US. The federal government directs the distribution of etesevimab and bamlanivimab together. Other details of the agreement have not been disclosed. ^{[15] [16] [17]}

In December 2020, Eli Lilly and Company entered into partnership with UnitedHealth Group (UnitedHealthcare Services) to conduct a pragmatic study of bamlanivimab in high-risk, COVID-2019 infected patients that meet Emergency Use Authorization (EUA) criteria as per the US FDA. Under the study design, UnitedHealth Group with its Optum health services will conduct a study in real world settings, which will detect high-risk symptomatic patients with COVID-2019 infections, including daily symptom tracking, in-home SARS-CoV-2 testing and in-home treatment with bamlanivimab infusion. The aim of the collaborative endeavour is to reduce the severity of illness and hospitalisations. The study will enroll up to 500 000 patients, with at least 5 000 people expected to receive bamlanivimab therapy. ^[18]

In November 2020, Samsung Biologics and Eli Lilly and Company entered into a long-term manufacturing agreement to accelerate global supply of COVID-19 antibody treatments. This agreement with Samsung supplements Lilly's own internal manufacturing capacity. Lilly and Samsung Biologics entered into the manufacturing partnership agreement in May 2020 to address the demand for COVID-19 treatments worldwide. Samsung was able to manufacture and deliver an initial supply of Active Pharmaceutical Ingredients (API) meeting Good Manufacturing Practices (GMP) and regulatory expectations within 5 months of contract signing. The timeline for tech transfer was less than 3 months ^[19]

In October 2020, Eli Lilly and Company and the Bill & Melinda Gates Foundation entered into an agreement to facilitate access to future Lilly therapeutic antibodies under development for the prevention and treatment of COVID-19, the disease caused by the SARS-CoV-2 novel coronavirus, to benefit low- and middle-income countries. Therapeutic antibodies have the potential to prevent and treat COVID-19, reducing the burden on healthcare systems worldwide. ^[20]

In September 2020, Eli Lilly and Company and Amgen entered a global antibody manufacturing collaboration to increase the supply capacity available for Lilly's potential COVID-19 therapies, including LY-CoV-555. Amgen will leverage its technical expertise in antibody development and its capabilities in the scale up and manufacturing of complex biologics. Further details of the agreement were not disclosed. ^[21]

In July 2020, Sanford Burnham Prebys Medical Discovery Institute entered into an research agreement with Eli Lilly and Company to characterize Lilly’s next-generation anti-SARS-CoV-2 antibodies. The research team will evaluate antibody candidates, delivered from Lilly through their partnership with AbCellera, using the live virus in the Institute’s Biosafety Level 3 (BSL-3) laboratory. ^[22]

As of May 2022, the US FDA announced that bamlanivimab and etesevimab combination was not currently authorized in any of the US regions due to high frequency of circulating SARS-CoV-2 variants that are non-susceptible to bamlanivimab and etesevimab hence should not be administered for the treatment or post-exposure prevention of COVID-19 under the Emergency Use Authorization until further notified by the FDA ^[1] . In January 2022, Elli Lilly and Company informed that the US FDA updated the authorization fact sheet for bamlanivimab and etesevimab combination for the treatment of mild to moderate COVID-19 as well as post-exposure prophylaxis, to include a new limitation stating that these therapies were not authorized in any US region due to its ineffectiveness at treating the predominant Omicron variant. The combination therapy is authorized to be administered together only for the treatment of mild to moderate COVID-19 in adults and pediatric patients, including neonates, with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death ^[23] . In September 2021, AbCellera announced that, the US FDA has expanded the EUA for bamlanivimab administered with etesevimab [see Adis Insight Drug profile800058525] to include post-exposure prophylaxis (PEP) to prevent COVID-2019 infection. The expanded EUA is based on data from the phase 3 BLAZE-2 trial [See below] ^{[24] [25]} . In December 2021, the US FDA expanded the Emergency Use Authorization (EUA) for bamlanivimab and etesevimab [see Adis Insight Drug profile 800058525] administered together to include pediatric patients under the age of 12, including neonates (infants <1 year old). The expanded EUA is based on data from the BLAZE-1 phase II/III clinical trial [see below]. Earlier in February 2021, the US FDA granted Emergency Use Authorization (EUA) for etesevimab and bamlanivimab combination therapy. The EUA request was submitted by Eli Lilly, in November 2020, based on the phase II/III BLAZE-1 trial data [see below] ^{[26] [27] [28] [29]}

In August 2021, Junshi Biosciences announced that the US FDA, alongside the Office of the Assistant Secretary for Preparedness and Response, has resumed the shipment and distribution of etesevimab and bamlanivimab [see Adis Insight Drug profile 800058899] combination therapy, for the treatment of mild to moderate COVID-2019 infection in high-risk patients ^[30] . In June 2021, the Assistant Secretary for Preparedness and Response (ASPR) halted shipment of bamlanivimab and etesevimab combination therapy as it does not retain neutralization effects against the gamma or beta variant, prevalent in the US ^[31]

In October 2021, company announced that withdrew rolling review of bamlanivimab in combination with etesevimab for the treatment of COVID-19 infections ^[32] . Earlier, the EMA to end the rolling review of bamlanivimab in combination with etesevimab for the treatment of COVID-19 infections, as the company is withdrawing it from the process. At the time of the company’s withdrawal, EMA had received non-clinical (laboratory) data, data from clinical studies, data on the quality and manufacturing process of the antibodies and the risk management plan (RMP). The withdrawal was a decision by the company and it retains the right to request another rolling review or submit a marketing authorisation application in the future ^[3] . In March 2021, CHMP started a rolling review of data on the antibodies bamlanivimab and etesevimab to be used in combination for the treatment of COVID-19 infections. The review will also look at bamlanivimab used alone ^[33] . Earlier, in March 2021, EMA CHMP issued a positive scientific opinion for bamlanivimab alone and bamlanivimab administered together with etesevimab [see Adis Insight Drug profile 800058525]. The CHMP opinion was based from the phase II and phase III BLAZE-1 trials [see below] ^[34] . Earlier, in February 2021, the bamlanivimab plus etesevimab [see Adis Insight Drug profile 800058525] regimen was authorized for use in Italy, for the treatment of mild to moderate COVID-2019 infections ^[27] . In the same month, the European Medical Agency's (EMA) human medicines committee (CHMP) initiated a rolling review of data on the use of bamlanivimab alone and in combination with etesevimab for the treatment of COVID-2019 infection in patients who do not require oxygen supplementation and who are at high risk of progressing to severe COVID-2019. The CHMP decision to start rolling review based on preliminary results from a study indicates that reduced the viral load in the back of the nose and throat of non hospitalized patients with COVID-19 who do not need supplementation oxygen ^[35] .

In April 2021, the US FDA revoked the emergency use authorisation (EUA) of bamlanivimab 700 mg alone, for the treatment of mild-to-moderate COVID-2019 infection in adults and certain paediatric patients, as the criteria for issuance of an authorisation were not met. The decision was made based on the scientific data, which included sustained increase of SARS-CoV-2 viral variants that were resistant to bamlanivimab alone which resulted in the increased risk for treatment failure ^[2] . In the same month, Eli Lilly and Company had requested the US FDA to revoke the Emergency Use Authorization (EUA). The request was made due to the evolving variant landscape in the US and the full availability of bamlanivimab and etesevimab [see Adis Insight Drug profile 800058525] together. This request was not due to any new safety concern. This was taken as a final step in Lilly's transition to only supply bamlanivimab and etesevimab together for administration in the US for the treatment of COVID-2019 infection– as planned with the US FDA – following the modification of contracts with the US government to ensure adequate supply of etesevimab to be used together with bamlanivimab. Additionally, there were no deaths reported and only 6% of patients were hospitalized ^{[36] [37]} . Previously in November 2020, AbCellera had announced that bamlanivimab 700 mg received an emergency use authorization (EUA) from the US FDA. Bamlanivimab is authorised for the treatment of mild to moderate COVID-19 in adults and paediatric patients 12 years and older with positive results of direct SARS-CoV-2 viral testing, who weigh at least 40 kg and are at high risk for progressing to severe COVID-19 and/or hospitalisation. The EUA is based on data from the two randomised trials namely; BLAZE-1 and BLAZE-2 [see below]. In February 2021, the infusion time was authorized at 16 minutes, significantly reduced from the previously approved time of 60 minutes. As of October 2020, Eli Lilly and Company submitted an initial request for emergency use authorization (EUA) to US FDA for bamlanivimab (LY CoV555) monotherapy in higher-risk patients who have been recently diagnosed with mild-to-moderate COVID-19 infection, based on the combination therapy data ^{[27] [38]} .

In February 2023, Eli Lily withdrew bamlanivimab for the treatment of COVID-2019 infections ^[39] . In November 2020, Health Canada granted authorisation to bamlanivimab under the interim order respecting the importation, sale and advertising of drugs for use in relation to COVID-19, as a treatment for adults and paediatric patients 12 years of age or older with mild to moderate COVID-19 who weigh at least 40 kg and are at high risk of progressing to severe COVID-19 illness and/or hospitalisation. This authorisation was based on data from BLAZE-1 trial [see below] ^[40] .

As of March 2021, Bamlanivimab alone is authorisd under special/emergency pathways in Czech Republic, Germany, Israel, Italy, Hungary, Sweden, Panama, Kuwait and UAE. In addition, bamlanivimab alone has been authorised for emergency use in Rwanda and Morocco, and through Lilly's work with the Bill & Melinda Gates Foundation, as company is providing doses of the medicine free of charge in these countries ^{[41] [42]} .

As of November 2020, Eli Lilly was in discussions with global regulators including from India, Brazil, Russia and Europe for pursuing authorisation of bamlanivimab for COVID-2019 infections ^[40] .

In July 2023, National Institute of Allergy and Infectious Diseases completed a phase III TICO (ACTIV-3) trial that evaluated the safety and efficacy of multiple investigational agents (either LY 3819253, remdesivir, VIR 7831, BRII 196/BRII 198, AZD 7442 and ensovibep) plus standard of care for the treatment of COVID-19 positive adults in the hospitalised setting (014 / ACTIV-3; NCT04501978; EudraCT2020-003278-37). The trial was designed as part of the National Institutes of Health’s (NIH) Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership. The randomised trial was inititaed in August 2020 and enrolled 2753 patients in Denmark, Greece, Poland, Singapore, Spain, Switzerland, Nigeria, Sweden, Italy, Uganda, United Kingdom and the US, However the trial was prematurely ended in Sweden and Italy ^[43] . In October 2022, Eli Lilly and company announced that no additional patients with COVID-2019 infections in the hospitalised setting will receive bamlanivimab. This recommendation was based on trial data suggesting that bamlanivimab is unlikely to help hospitalized patients with COVID-2019 infections recover from this advanced stage of their disease ^{[44] [45]} .

In November 2020, Eli Lilly and company completed an expanded access programme for COVID-2019 infections in the US. In October 2020, Eli Lilly Company initiated an expanded access programme for COVID-2019 infections in the US (18165; J2X-MC-Y001; NCT04603651) ^[46] .

In June 2023, National Institute of Allergy and Infectious Diseases completed phase-II/III ACTIV-2 adaptive trial that evaluated the safety and efficacy of different drugs, including Camostat mesylate [see Adis Insight Drug profile 800004886], Interferon beta 1a [see Adis Insight Drug profile 800024480], SAB 185 [see Adis Insight Drug profile 800058161], Bamlanivimab, Amubarvimab/romlusevimab [see Adis Insight Drug profile 500059605], Cilgavimab/tixagevimab [see Adis Insight Drug profile 800059900], Ogalvibart/C 144LS [see Adis Insight Drug profile 800062239] in outpatients with COVID-2019 infections (NCT04518410; A5401ACTIV2). The randomised, blinded, placebo-controlled trial initiated in August 2020 and enrolled 4044 patients in the US, Argentina, Brazil, Canada, South Africa, Mexico, Philippines and Puerto Rico700326876. In February 2022, Eli Lilly presented results from phase-II/III trial at the 29^th Conference on Retroviruses and Opportunistic Infections ^[47] .

In May 2021, Eli Lilly, in collaboration with AbCellera Biologics and National Institute of Allergy and Infectious Diseases, completed a phase III BLAZE-2 trial that evaluated bamlanivimab alone and in combination with etesevimab (LY 3832479/LY CoV016) [see Adis Insight Drug profile800058525] to prevent COVID-2019 infections (NCT04497987; 18063; J2X-MC-PYAD; CoVPN #3501). The randomised study was initiated in August 2020 and enrolled 1374 participants in the US. The study was run jointly with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). In August 2020, National Institute of Allergy and Infectious Diseases reported that enrollment of healthy adults who are at risk of infection due to close contact at work or home to persons with SARS-CoV-2 infection in the trial has been initiated in the US ^{[48] [49] [50]} . In January 2021, results from the trial were released by the company ^{[51] [52]} . In January 2021, efficacy data from a trial in COVID-2019 infections was released by Eli Lilly and Company. In March 2021, Eli Lilly and Company presented safety and efficacy data from a phase III trial at the 28^th Conference on Retroviruses and Opportunistic Infections (CROI-2021) ^{[53] [54]} .

In June 2021, Eli Lilly and Company in collaboration with AbCellera Biologics completed the phase II BLAZE-5 trial which evaluated the real-world effectiveness of bamlanivimab in patients with mild-to-moderate COVID-2019 infections (NCT04701658; J2X-MC-PYAJ; 18216). The open-label, prospective cohort trial was initiated in February 2021 and enrolled 3000 patients in the US ^[55] .

In October 2021, Eli Lilly and Company completed a phase II BLAZE-4 trial evaluating the efficacy and safety of etesevimab (LY 3832479/LY CoV016) [see Adis Insight Drug profile800058525] and bamlanivimab (LY 3819253/LY CoV555) as monotherapy and combination therapy in patients with mild to moderate COVID-2019 infections (NCT04634409; J2X-MC-PYAH). The randomised, placebo-controlled trial initiated in October 2020, enrolled 1631 patients in the US, Argentina and Puerto Rico ^{[56] [57]} . In January 2021, Eli Lilly expanded the trial to evaluate bamlanivimab in combination with sotrovimab [see Adis Insight Drug profile800058114] in patients with mild to moderate COVID-2019 infections. Subsequently, first patient was dosed in the trial ^[8] . In March 2021, Eli lilly and company reported that the BLAZE-4 trial met primary end point in which combination of bamlanivimab, 700mg with sotrovimab, 500mg showed significant reduction in high viral load by 70% (> 5.27; cycle threshold value < 27.5) at day 7 compared with placebo ^{[58] [27]} . In September 2021, Eli Lilly reported that the trial has completed patient enrollment ^{[14] [13]}

In January 2021, the phase II/III BLAZE-1 trial met the primary and secondary endpoints of the study by significantly reducing viral load and accelerated symptom resolution with the combination therapy of bamlanivimab and etesevimab, in patients with COVID-2019 infections (17947; J2W-MC-PYAB; NCT04427501). In February 2023, Eli Lilly, in collaboration with AbCellera Biologics, completed the trial that evaluated safety and efficacy of bamlanivimab alone and in combination with etesevimab [see Adis Insight Drug profile 800058525]. The randomised, double-blind, placebo-controlled was initiated in June 2020 and enrolled 3307 patients in the US ^[59] . In September 2020, interim safety and efficacy results from the trial were released by the company ^[60] . In October 2020, the company released the interim analysis of the trial ^[29] . In January and March 2021, the company released additional data from the trial. In March 2021, Eli Lilly and Company released efficacy and adverse events data from a phase II/III trial at the 28^th Conference on Retroviruses and Opportunistic Infections (CROI-2021) ^{[41] [28]} . In February 2022, additional results were presented at the 29th Conference on Retroviruses and Opportunistic Infections (CROI-2022) ^[61]

In August 2020, Eli Lilly completed a phase I trial that evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of bamlanivimab in patients with COVID-2019 infections (17823; J2W-MC-PYAA; NCT04411628). The randomised, double-blind placebo-controlled trial was initiated in May 2020 and enrolled approximately 24 patients in the US ^[62] . In September 2020, Eli Lilly has successfully completed enrollment in the trial and primary safety assessments of LY CoV 555 ^{[60] [63] [64]} .

In December 2020, Eli Lilly and Company completed a phase I trial that evaluated the pharmacokinetics, safety, and tolerability of bamlanivimab, administered subcutaneously in healthy volunteers (NCT04537910; 18124; J2X-MC-PYAG). The randomised, placebo-controlled, double-blind study was initiated in September 2020 and enrolled approximately 25 volunteers in the US ^[65] .

In April 2021, AbCellera reported results from the preclinical studies ^[66] .

In preclinical studies, all resistant viruses, except the Q493R variant were neutralised by bamlanivimab and etesevimab [see Adis Insight Drug profile 800058525] combination therapy. Neutralisation and binding assessments also confirmed reduced susceptibility of the variants to the single selecting mAb with 50-fold or greater reductions in potency ^[67] .

As of March 2020, early research development for COVID-2019 treatment is underway in Canada ^[5] .