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 to prevent and treat COVID-19. Lilly scientists rapidly developed the antibody in less than three months after being 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 BLAZE-1 clinical trial.
Bamlanivimab COVID-19 Treatment History
On November 9, 2020, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for the bamlanivimab to treat mild-to-moderate COVID-19 in adult and pediatric patients. While this investigational therapy's safety and effectiveness 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 stated 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 evaluates 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.'
On November 9, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) to make bamlanivimab available to treat nonhospitalized patients with mild to moderate COVID-19 who are at high risk for progressing to severe disease and/or hospitalization. The issuance of a EUA does not constitute FDA approval of a product. The COVID-19 Treatment Guidelines Panel reviewed the available evidence from the published data on bamlanivimab for the treatment for COVID-19 and the FDA fact sheet that supported the EUA, said the NIH.
The company announced a new purchase agreement with the US government on December 2, 2020, for $812.5 million. The bamlanivimab doses will be delivered through January 31, 2021, with at least 350,000 additional doses delivered in December 2020.
David A. Ricks, Lilly's chairman, and CEO stated in a press release: "We are proud of our work to deploy significant manufacturing capacity and remain committed to enabling widespread and equitable access to bamlanivimab. The U.S. government's effort to allocate bamlanivimab around the country is critical to ensuring it reaches patients who need it the most."
Lilly is a global healthcare leader who unites caring with discovery to create medicines that make life better for people worldwide. To learn more about Lilly, please visit us at www.lilly.com.
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 65 years of age or older or certain chronic medical conditions. Bamlanivimab is not authorized for hospitalized patients due to COVID-19 or require oxygen therapy due to COVID-19.
The FDA has not approved Bamlanivimab for any use. It is unknown if bamlanivimab is safe and effective for the treatment of COVID-19. Healthcare providers should review the Fact Sheet for information on the authorized use of bamlanivimab and mandatory requirements of the EUA.
Bamlanivimab COVID-19 Treatment Adverse Events
Adverse events reported in at least 1% of BLAZE-1 clinical trial participants on bamlanivimab 700 mg and placebo were Nausea (3% vs 4%), Diarrhea (1% vs 5%), Dizziness (3% vs 2%), Headache (3% vs 2%), Pruritus (2% vs 1%) and Vomiting (1% vs 3%).
Bamlanivimab COVID-19 Treatment Safety Information
There are limited clinical data available for bamlanivimab. Serious and unexpected adverse events may occur that have not been previously reported with bamlanivimab use. Infusion-related reactions have been observed with the administration of bamlanivimab.
There is a potential for serious hypersensitivity reaction, including anaphylaxis, with the administration of bamlanivimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care.
There are insufficient data on the use of bamlanivimab during pregnancy. Bamlanivimab should only be used during pregnancy if the potential benefit outweighs the mother and fetus's potential risk.
There are no available data on the presence of bamlanivimab in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.
Bamlanivimab COVID-19 Treatment Guidelines
Eli Lilly says, 'If you’ve recently been diagnosed with COVID-19, you may have a new treatment option: bamlanivimab (bam-la-NIV-i-mab). The research so far shows that taking this drug may help limit the amount of virus in the body for certain people. This may help their symptoms improve sooner — and they may be less likely to need to go to the hospital. But bamlanivimab is a new drug that’s still being studied, so there’s a lot that scientists don’t know about the benefits and risks. Together, you and your doctor can decide if this treatment is right for you.'
The U.S. NIH COVID-19 Treatment Guidelines Panel’s Statement on the Emergency Use Authorization of Bamlanivimab for the Treatment of COVID-19. Last Updated: November 18, 2020.
Bamlanivimab COVID-19 Treatment News
January 21, 2021 - Eli Lilly and Company's Bamlanivimab (LY-CoV555) significantly reduced the risk of contracting symptomatic COVID-19 among residents and staff of long-term care facilities, according to the Phase 3 BLAZE-2 COVID-19 prevention trial. After all of the study participants reached 8 weeks of follow-up, there was a significantly lower frequency of symptomatic COVID-19 (the primary endpoint) in the bamlanivimab treatment arm versus placebo (odds ratio 0.43, p=0.00021). All key secondary endpoints also reached statistical significance in both the overall and resident populations.
January 21, 2021 - JAMA Network Original Investigation - Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19. A Randomized Clinical Trial Conclusions and Relevance: 'Among nonhospitalized patients with mild to moderate COVID-19 illness, treatment with bamlanivimab and etesevimab, compared with placebo, was associated with a statistically significant reduction in SARS-CoV-2 viral load at day 11. No significant difference in viral load reduction was observed for bamlanivimab monotherapy. Further ongoing clinical trials will focus on assessing the clinical benefit of antispike neutralizing antibodies in patients with COVID-19 as a primary endpoint.'
December 28, 2020 - Governor Greg Abbott and the Texas Department of State Health Services are alerting nursing facilities to the availability of monoclonal antibody therapies that can be used to treat residents who have been diagnosed with COVID-19. Commissioner John Hellerstedt, MD, urges facility administrators to work with their medical directors and treating physicians to consider the use of monoclonal antibodies whenever appropriate. These therapeutics have shown promise in reducing hospital admissions for patients who have been diagnosed with the disease, have a mild or moderate illness and are in a high-risk group for developing severe disease.
December 18, 2020 - Eli Lilly and Company announced plans to begin a new pragmatic study of bamlanivimab (LY-CoV555) in high-risk patients with COVID-19, collaborating with major local institutions in the state of New Mexico. Conducting the study in New Mexico will allow for collecting data on the effectiveness and safety of bamlanivimab in a real-world setting that includes a diverse population and spans both rural and urban environments.
December 11, 2020 - JAMA article: he investigational neutralizing IgG1 monoclonal antibody bamlanivimab (LY-CoV555; Lilly) has been granted an FDA Emergency Use Authorization (EUA) for treatment of recently diagnosed mild to moderate COVID-19 in patients who are ≥12 years old, weigh at least 40 kg, and are at high risk for progressing to severe disease and/or hospitalization.
December 4, 2020 - Eli Lilly and UnitedHealth Group announced a partnership to conduct a pragmatic study of bamlanivimab (LY-CoV555) in high-risk, COVID-19 infected individuals. The study will identify and treat a large, diverse population of high-risk individuals for COVID-19 with bamlanivimab under real-world conditions to reduce the severity of illness and hospitalizations. It will draw upon both UnitedHealth Group's UnitedHealthcare health benefits business and its Optum health services business to detect and treat high-risk symptomatic patients who test positive for COVID-19, including daily symptom tracking, in-home SARS-CoV-2 testing, and in-home infusion services.
December 2, 2020 - The U.S. government has purchased 650,000 additional doses of the neutralizing antibody bamlanivimab (LY-CoV555) 700 mg. The doses will be delivered through January 31, 2021, with at least 350,000 additional doses delivered in December 2020. Bamlanivimab recently received emergency use authorization to treat mild to moderate COVID-19 in patients at high risk for progressing to severe COVID-19 and/or hospitalization. This purchase brings the total doses purchased by the U.S. government to 950,000. As previously announced by the U.S. government, Americans will have no out-of-pocket costs for the medicine, although healthcare facilities may charge a fee for the product's administration.
November 24, 2020 - 1st patient receiving Covid-19 antibody infusion at El Paso Convention Center hospital announced. The alternate care site was provided with 1,000 doses of bamlanivimab, a monoclonal antibody therapy created by Eli Lilly & Company recently approved for emergency use by the FDA.
November 20, 2020 - Health Canada granted authorization under the Interim Order Respecting the Importation, Sale, and Advertising of Drugs for Use concerning 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 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). It 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 communicate with the trial sponsor regarding the recommendation from the independent data safety monitoring board (DSMB) of the ACTIV-3 clinical trial to pause the study's enrollment. ACTIV-3, which evaluates Lilly’s investigational neutralizing antibody bamlanivimab (LY-CoV555) as a treatment for COVID-19 in hospitalized patients, is sponsored by the National Institute 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 had 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) 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, protects 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 hospitalization rate 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 had 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.
- 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 simultaneously, 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 that do not reach the stage 1 intermediate outcomes' effectiveness threshold, 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 study.
- Investigational drugs with reasonably well-established safety profiles and evidence of effectiveness (i.e., at least equivalent to the criteria for advancing 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: December 19, 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 binds complementary regions of the SARS-CoV-2 spike protein treatment symptomatic COVID-19 in the outpatient setting.
- The combination therapy significantly reduced viral load at day 11 (p=0.011), meeting the study's primary endpoint. 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 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). Last Update Posted: November 10, 2020.
- 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.