January 27, 2021: Eli Lilly and Company, Vir Biotechnology, Inc. and GlaxoSmithKline plc announced a collaboration to evaluate a combination of two COVID-19 therapies in low-risk patients with mild to moderate COVID-19.
Lilly has expanded its ongoing BLAZE-4 trial to evaluate the administration of bamlanivimab (LY-CoV555) 700mg with VIR-7831 (also known as GSK4182136) 500mg, two neutralizing antibodies that bind to different epitopes of the SARS-CoV-2 spike protein.
This unique collaboration marks the first time that monoclonal antibodies from separate companies will be brought together to explore potential outcomes.
Bamlanivimab is a neutralizing antibody directed against the spike protein of SARS-CoV-2 designed to block viral attachment and entry into human cells, thus neutralizing the virus.
Bamlanivimab emerged from the collaboration between Lilly and AbCellera to create antibody therapies for the prevention and treatment of COVID-19.
Bamlanivimab is authorized for emergency use for the treatment of mild to moderate COVID-19 in patients who are at high risk for progressing to severe COVID-19 and/or hospitalization.
VIR-7831 is a dual-action monoclonal antibody that was selected for clinical development based on its potential to both block viral entry into healthy cells and clear infected cells, as well as its potential to provide a high barrier to resistance.
In pre-clinical trials, the antibody has shown the ability to neutralize the SARS-CoV-2 live virus by binding to an epitope on SARS-CoV-2 shared with SARS-CoV-1, indicating that the epitope is highly conserved, which may make it more difficult for escape mutants to develop.
Vir and GSK are advancing VIR-7831 as part of their collaboration to research and develop solutions for coronaviruses, including SARS-CoV-2.
“Bamlanivimab is a potent antibody – with data from multiple Phase 2 and 3 clinical trials, which have demonstrated robust evidence for both treating and preventing COVID-19,” said Daniel Skovronsky, M.D., Ph.D., Lilly’s chief scientific officer and president of Lilly Research Laboratories. “With a virus like SARS-CoV-2, it’s expected that variants could emerge that require new therapeutic options, which is why Lilly is studying bamlanivimab together with other neutralizing antibodies, including etesevimab.
Adding VIR-7831 to our study is an important part of our commitment to develop therapies to treat current and future strains of COVID-19 until vaccines are widely available and utilized.”
“We believe that VIR-7831 has significant potential as a single agent, and we are optimistic about the pending interim data from two Phase 3 trials evaluating its potential for early treatment and in hospitalized patients,” said George Scangos, Ph.D., chief executive officer of Vir. “As the virus continues to evolve, we, along with Lilly and GSK, share the view that we should pursue all possibilities to help end the pandemic and maximize the number of lives that can be saved.
This trial is a first step to assess whether the administration of VIR-7831, with its high barrier to resistance and potent effector function, alongside bamlanivimab, which has strong outcomes data in early treatment, can provide potential benefits beyond monotherapy.”
“Despite the significant progress on vaccines, there remains an urgent patient need for multiple therapeutic approaches to help prevent the severe consequences of COVID-19,” said Dr. Hal Barron, chief scientific officer and president R&D of GSK.
“Partnering with Lilly to study VIR-7831 with bamlanivimab will provide the scientific community with further data on the important role these therapies could play in reducing the impact of this devastating pandemic.”
Bamlanivimab alone has been granted Emergency Use Authorization (EUA) by the U.S. FDA based on interim data from the Phase 2 BLAZE-1 trial, which was published in the New England Journal of Medicine.
These data show the therapy may help patients clear the virus and reduce COVID-19-related hospitalizations when given early in the disease course. The safety and efficacy of bamlanivimab is being evaluated with other neutralizing antibodies to provide a possible safeguard against potential viral resistance.
VIR-7831 is an investigational compound, not approved by the U.S. FDA or any other regulatory authority.
VIR-7831 is also being evaluated in the global Phase 2/3 COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early) trial for the early treatment of COVID-19 in adults at high risk of hospitalization.
Important Information about bamlanivimab
Bamlanivimab has not been approved by the FDA for any use. It is not known if bamlanivimab is safe and effective for the treatment of COVID-19.
Bamlanivimab is authorized under an Emergency Use Authorization only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of bamlanivimab under Section 564(b)(1) of the Act, 21 U.S.C § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.
Healthcare providers should review the Fact Sheet for information on the authorized use of bamlanivimab and mandatory requirements of the EUA.
Please see the FDA Letter of Authorization, Fact Sheet for Healthcare Providers, and Fact Sheet for Patients, Parents, and Caregivers (English) (Spanish).
Authorized Use and Important Safety Information
Bamlanivimab 700 mg injection is authorized for use under EUA for treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization.
Limitations of Authorized Use
- Bamlanivimab is not authorized for use in patients:
- who are hospitalized due to COVID-19, OR
- who require oxygen therapy due to COVID-19, OR
- who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity.
- who are hospitalized due to COVID-19, OR
- Benefit of treatment with bamlanivimab has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as bamlanivimab, may be associated with worse clinical outcomes when administered to hospitalized patients requiring high flow oxygen or mechanical ventilation with COVID-19.
Important 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.
Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions
There is a potential for serious hypersensitivity reaction, including anaphylaxis, with 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.
Infusion-related reactions have been observed with administration of bamlanivimab. Signs and symptoms of infusion-related reactions may include:
- fever, chills, nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness.
If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care.
Limitations of Benefit and Potential Risk in Patients with Severe COVID-19
Benefit of treatment with bamlanivimab has not been observed in patients hospitalized due to COVID-19.
Monoclonal antibodies, such as bamlanivimab, may be associated with worse clinical outcomes when administered to hospitalized patients requiring high flow oxygen or mechanical ventilation with COVID-19.
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%).
Use in Specific Populations
Pregnancy
There are insufficient data on the use of bamlanivimab during pregnancy.
Bamlanivimab should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus.
Breastfeeding
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.
About BLAZE-4
BLAZE-4 (NCT04634409) is a randomized, double-blind, placebo-controlled trial designed to assess the efficacy and safety of bamlanivimab alone, and bamlanivimab with other neutralizing antibodies including VIR-7831 (GSK4182136) versus placebo for the treatment of symptomatic COVID-19 in the outpatient setting.
Across all treatment arms, the trial will enroll an estimated 1,000 participants in the United States and Puerto Rico.
The primary outcome measure is percentage of participants who have a viral load greater than 5.27 at day 7.
Additional endpoints include change from baseline to day 7 in SARS-CoV-2 viral load, percentage of participants who experience COVID-related hospitalization, ER visit or death from baseline through day 29, as well as safety.”
