Bamlanivimab COVID-19 Treatment Description
Bamlanivimab (LY-CoV555) is an investigational neutralizing IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2. It is designed to block viral attachment and entry into human cells, thus neutralizing the virus, potentially preventing and treating COVID-19.
Bamlanivimab emerged from the collaboration between Lilly and AbCellera to create antibody therapies for the prevention and treatment of COVID-19. Lilly scientists rapidly developed the antibody in less than three months after it was discovered by AbCellera and tested by the scientists at the NIAID Vaccine Research Center.
In addition to Bamlanivimab a second Lilly antibody, LY-CoV016, which binds a different epitope in the SARS-CoV-2 spike region has been added to the BLAZE-1 clinical trial.
On November 9, 2020, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for the bamlanivimab for the treatment of mild-to-moderate COVID-19 in adult and pediatric patients. While the safety and effectiveness of this investigational therapy continue to be evaluated, bamlanivimab was shown in clinical trials to reduce COVID-19-related hospitalization or emergency room visits in patients at high risk for disease progression within 28 days after treatment when compared to placebo.
Previously, on October 1, 2020, a non-peer-reviewed study found 'In a rhesus macaque challenge model, prophylaxis Bamlanivimab doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract. These data demonstrate that high-throughput screening can lead to the identification of a potent antiviral antibody that protects against SARS-CoV-2 infection.'
On October 14, 2020, Lilly issued a statement on the National Institute of Allergy and Infectious Diseases (NIAID) Decision to Pause Enrollment in ACTIV-3 Clinical Trial: 'Lilly continued to be in communication with the trial sponsor regarding the recommendation from the independent data safety monitoring board (DSMB) of the ACTIV-3 clinical trial to pause enrollment of the study. ACTIV-3, which is evaluating Lilly’s investigational neutralizing antibody bamlanivimab (LY-CoV555) as a treatment for COVID-19 in hospitalized patients, is sponsored by the NIAID, part of the National Institutes of Health (NIH).
Lilly continued stating: 'At this time, only the DSMB has reviewed the data from the trial, and NIH leadership and Lilly remain blinded to the ongoing trial results. Lilly trusts the judgment of the independent DSMB and supports its decisions to exercise caution in ensuring the safety of the patients participating in this study. Importantly, the DSMB also considered the impact of the ACTIV-3 study pause on ACTIV-2 and did not recommend any changes to that study’s design or enrollment.'
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Bamlanivimab COVID-19 Treatment Indication
Bamlanivimab (LY-CoV555) is indicated to prevent or mitigate the progression of COVID-19 infection caused by the SARS-CoV-2 coronavirus. As of November 9, 2020, Bamlanivimab was authorized for patients with positive results of direct SARS-CoV-2 viral testing who are 12 years of age and older weighing at least 40 kilograms (about 88 pounds), and who are at high risk for progressing to severe COVID-19 and/or hospitalization.
Bamlanivimab should be administered as soon as possible after a positive COVID-19 test and within 10 days of symptom onset.
This EAU includes those who are 65 years of age or older, or who have certain chronic medical conditions. Bamlanivimab is not authorized for patients who are hospitalized due to COVID-19 or require oxygen therapy due to COVID-19.
Bamlanivimab COVID-19 Treatment News
November 20, 2020 - Health Canada granted authorization under the Interim Order Respecting the Importation, Sale, and Advertising of Drugs for Use in Relation to COVID-19 for the use of bamlanivimab (LY-CoV555) as a treatment for adults and pediatric 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 hospitalization. This authorization, the second authorization around the world for bamlanivimab, is based on data from BLAZE-1, a randomized, double-blind placebo-controlled phase 2 study in patients with recently diagnosed, mild to moderate COVID-19.
November 19, 2020 - Texas Governor Greg Abbott updated the distribution of bamlanivimab, the Eli Lilly & Company monoclonal antibody therapy for COVID-19. The Texas Department of State Health Services has allocated this initial shipment of bamlanivimab to acute care hospitals across Texas
November 13, 2020 - A new study in Italy found Baricitinib as possessing anti-viral and anti-cytokine efficacy. This limited study showed a 71% (95% CI 0.15-0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia, with few drug-induced adverse events, including a large elderly cohort (median age 81 years).
November 9, 2020 - Eli Lilly announced the U.S. FDA granted Emergency Use Authorization for the investigational neutralizing antibody bamlanivimab (LY-CoV555) 700 mg. The authorization allows for the distribution and emergency use of bamlanivimab, which is administered via a single intravenous infusion
October 28, 2020 - Eli Lilly and Company announced an initial agreement with the U.S. government to supply 300,000 vials of bamlanivimab (LY-CoV555) 700 mg, an investigational neutralizing antibody, for $375 million. The initial agreement is for delivery over the two months following authorization and also provides the option for the U.S. government to purchase up to an additional 650,000 vials through June 30, 2021.
October 26, 2020 - The ACTIV-3 clinical trial is being run by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and is the only study evaluating the efficacy of bamlanivimab in hospitalized COVID-19 patients. Based on an updated dataset from the trial reviewed on October 26, no additional COVID-19 patients in this hospitalized setting will receive bamlanivimab. This recommendation was based on trial data suggesting that bamlanivimab is unlikely to help hospitalized COVID-19 patients recover from this advanced stage of their disease. In this updated dataset, differences in safety outcomes between the groups were not significant.
October 14, 2020 - Lilly announced it continues to be in communication with the trial sponsor regarding the recommendation from the independent data safety monitoring board (DSMB) of the ACTIV-3 clinical trial to pause enrollment of the study. ACTIV-3, which is evaluating Lilly’s investigational neutralizing antibody bamlanivimab (LY-CoV555) as a treatment for COVID-19 in hospitalized patients, is sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. At this time, only the DSMB has reviewed the data from the trial, and NIH leadership and Lilly remain blinded to the ongoing trial results. Lilly trusts the judgment of the independent DSMB and supports its decisions to exercise caution in ensuring the safety of the patients participating in this study.
October 13, 2020 - Eli Lilly and Co said that the government-sponsored clinical trial of its COVID-19 antibody treatment has been paused because of a safety concern.
October 8, 2020 - Junshi Biosciences announced that its global partner Eli Lilly and Company announced positive interim data on combination therapy with neutralizing antibodies JS016 (LY-CoV016) and LY-CoV555 in recently diagnosed patients with mild-to-moderate COVID-19 illness. Lilly intends to submit a request for Emergency Use Authorization (EUA) for the combination therapy in patients with mild-to-moderate COVID-19 in November 2020.
October 7, 2020 - Lilly provides a comprehensive update on the progress of SARS-CoV-2 neutralizing antibody programs.
October 1, 2020 - Non-peer-reviewed study: LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection.
September 16, 2020 - Lilly announced a proof of concept data from an interim analysis of the BLAZE-1 clinical trial, showing a reduced rate of hospitalization for patients treated with LY-CoV555.
August 3, 2020 - Lilly Initiates Phase 3 Trial of LY-CoV555 for Prevention of COVID-19 at Long-Term Care Facilities in Partnership with the National Institute of Allergy and Infectious Diseases (NIAID).
June 1, 2020 - Eli Lilly and Company announced patients have been dosed in the world's first study of a potential antibody treatment designed to fight COVID-19.
Bamlanivimab COVID-19 Treatment Clinical Trials
Clinical Trial NCT04501978: ACTIV-3: Therapeutics for Inpatients With COVID-19 (TICO). Last Update Posted: November 9, 2020.
- The Phase 3 randomized, controlled trial is known as ACTIV-3, and as a “master protocol,” it is designed to expand to test multiple different kinds of monoclonal antibody treatments. It also can enroll additional volunteers in the middle of the trial, if a specific investigational treatment shows promise.
- The protocol is for a randomized, blinded, controlled platform study that allows investigational drugs to be added and dropped during the course of the study. This allows for efficient testing of new drugs against placebo and standard of care (SOC) treatment within the same study. When more than one drug is being tested at the same time, participants will be randomly allocated to treatments or placebo.
- This platform study involves 2 stages. In stage 1, safety will be evaluated and two intermediate outcomes will be assessed to determine whether a drug advances to stage 2. Treatments considered to have demonstrated unacceptable risks relative to benefits, or those which do not reach the effectiveness threshold for the stage 1 intermediate outcomes, will not advance to stage 2. In some cases, stage 1 may include 2 or 3 doses of the same investigational drug, which will be considered separate drugs for the purpose of the study.
- Investigational drugs with reasonably well-established safety profiles and evidence of effectiveness (i.e. at least equivalent to the criteria for the advancement of a drug from stage 1 to stage 2) may enter the study directly at stage 2. Conversely, for drugs with minimal pre-existing safety evidence, the pace of stage 1 will initially be restricted and there will be an early review of safety data by an independent Data and Safety Monitoring Board (DSMB). A Phase 1 dose-escalation study for some investigational drugs may be required, and if so, the Phase 1 study would precede stage 1 and be carried out as a separate protocol.
- The international trials within this protocol will be conducted in several hundred clinical sites. Participating sites are affiliated with networks funded by the United States National Institutes of Health (NIH) and the US Department of Veterans Affairs.
Clinical Trial NCT04411628: A Study of LY3819253 (LY-CoV555) in Participants Hospitalized for COVID-19. Last Update Posted: October 30, 2020
- The purpose of this study is to test the safety and tolerability of LY3819253 when it is given by injection into a vein to participants hospitalized with COVID-19.
- Blood tests will be done to check how much LY3819253 is in the bloodstream and how long the body takes to eliminate it. Participation could last about 8 weeks and may include up to 15 visits to the hospital or the home.
Clinical Trial NCT04427501: A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness (BLAZE-1). Last Update Posted: September 18, 2020
- The purpose of this study is to measure how well LY3819253 and LY3832479 work against the virus that causes COVID-19. LY3819253 and LY3832479 will be given to participants with early symptoms of COVID-19, via an injection into a vein.
- Data from a new interim analysis of the BLAZE-1 clinical trial showed that combination therapy with two of Lilly's SARS-CoV-2 neutralizing antibodies reduced viral load, symptoms, and COVID-related hospitalization and ER visits. The randomized, double-blind, placebo-controlled Phase 2 study evaluated LY-CoV555 and LY-CoV016, which bind complementary regions of the SARS-CoV-2 spike protein, for the treatment of symptomatic COVID-19 in the outpatient setting.
- The combination therapy significantly reduced viral load at day 11 (p=0.011), meeting the primary endpoint of the study. Most patients, including those receiving placebo, demonstrated near-complete viral clearance by day 11. Further, combination treatment reduced viral levels at day 3 (p=0.016) and day 7 (p<0.001)—earlier time points during the course of infection when higher viral loads are typically seen. Combination therapy also significantly reduced the time-weighted average change from baseline from day 1 to 11. An exploratory analysis showed that the proportion of patients with persistent high viral load at day 7 for combination therapy was lower (3.0 percent) versus placebo (20.8 percent), corresponding to a nominal p-value of p<0.0001 without multiplicity adjustment. No emergent putative resistance variants have been observed thus far in patients treated with combination therapy.
Clinical Trial NCT04497987: A Study of LY3819253 (LY-CoV555) in Preventing SARS-CoV-2 Infection and COVID-19 in Nursing Home Residents and Staff (BLAZE-2)
- The purpose of this study is to evaluate whether LY3819253 prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease - 2019 (COVID-19) in facility staff and residents in contracted skilled nursing and assisted living facility networks with a high risk of SARS-CoV-2 exposure.
- Participants with a high risk of SARS-CoV-2 exposure will receive LY3819253 or placebo administered intravenously.