Lilly announces procurement agreement with European Commission to supply bamlanivimab and etesevimab together for the treatment of confirmed COVID-19

INDIANAPOLIS, Sept. 21, 2021 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced a Joint Procurement Agreement with the European Commission (EC) to supply up to 220,000 doses of bamlanivimab and etesevimab for the treatment of confirmed COVID-19 in patients aged 12 years and older who do not require supplemental oxygen for COVID-19 and who are at increased risk of progressing to severe COVID-19. This agreement helps to provide access to treatments by enabling participating countries in the European Union (EU) and European Economic Area (EEA) to purchase the products directly from Lilly, following national approval for emergency use, or marketing authorization at the EU level. Quantities purchased may vary based on local needs as determined by participating countries.

This action follows the scientific opinion under Article 5(3) of Regulation 726/2004 issued by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) in March supporting the use of these antibodies as a treatment for COVID-19 in patients aged 12 and older. The CHMP scientific opinion supports national decision-making within EU member states on the use of treatments before a formal marketing authorization is granted, during a public health emergency. 

"Bamlanivimab and etesevimab have played an important role in the fight against COVID-19, helping hundreds of thousands of patients globally," said Alfonso Zulueta, senior vice president and president, Lilly International. "Lilly is pleased to have reached this agreement with the European Commission which opens the door for many European countries to access this life-saving treatment option for patients with COVID-19."

Preclinical data from our labs have demonstrated that bamlanivimab and etesevimab administered together retain neutralization activity against variants currently in circulation in many countries, including Delta and Alpha. Based on the high transmissibility of the Delta variant, currently over 95 percent of new COVID-19 infections in the EU/EEA have been identified as being caused by the Delta variant.

Bamlanivimab administered with etesevimab is available under emergency pathways in 15 countries around the world for the treatment of COVID-19.

While a number of European countries have previously ordered bamlanivimab and etesevimab from Lilly in the first half of the year, and have inventory on hand, this agreement provides access to additional doses for participating countries, should they be needed. Lilly does not anticipate an impact to 2021 guidance as a result of this agreement.

Important Information about bamlanivimab and etesevimab together
Bamlanivimab and etesevimab together have not received marketing authorization in the EU and has not been approved by the FDA for any use.  It is not known if bamlanivimab and etesevimab together are safe and effective for the treatment or post-exposure prophylaxis of COVID-19. 

Bamlanivimab and etesevimab together are authorized under Emergency Use Authorization in the United States, only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use under Section 564(b)(1) of the Act, 21 U.S.C § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

U.S. Authorized Use and Important Safety Information
TREATMENT
Bamlanivimab and etesevimab together are authorized for the treatment of mild to moderate coronavirus disease 2019 (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 progression to severe COVID-19, including hospitalization or death.

Limitations of Authorized Use: Treatment
Combined Frequency of Variants Resistant to Bamlanivimab and Etesevimab

• Bamlanivimab and etesevimab are not authorized for use in states, territories, and US jurisdictions in which the combined frequency of variants resistant to bamlanivimab and etesevimab exceeds 5%.ⁱ
• A list of states, territories, and US jurisdictions in which bamlanivimab and etesevimab are and are not currently authorized is available on the following FDA website.

Use in Patients Who Are Hospitalized or Who Require Oxygen Due to COVID-19
Bamlanivimab and etesevimab together are 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.

Treatment with bamlanivimab and etesevimab together has not been studied in patients hospitalized due to COVID-19. Monoclonal antibodies, such as bamlanivimab and etesevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation.

POST-EXPOSURE PROPHYLAXIS
Bamlanivimab and etesevimab administered together are authorized for post-exposure prophylaxis of COVID-19 in adults and pediatric individuals (12 years of age or older weighing at least 40 kg) who are at high risk for progression to severe COVID-19, including hospitalization or death, and are:

• not fully vaccinatedⁱⁱ or who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination (for example, individuals with immunocompromising conditions including those taking immunosuppressive medicationsⁱⁱⁱ) and
• have been exposed to an individual infected with SARS-CoV-2 consistent with close contact criteria per Centers for Disease Control and Prevention (CDC)^iv or
• who are at high risk of exposure to an individual infected with SARS-CoV-2 because of occurrence of SARS-CoV-2 infection in other individuals in the same institutional setting (for example, nursing homes, prisons).

Limitations of Authorized Use: Post-Exposure Prophylaxis

• Bamlanivimab and etesevimab are not authorized for use in states, territories, and US jurisdictions in which the combined frequency of variants resistant to bamlanivimab and etesevimab exceeds 5%. ⁱ
• A list of states, territories, and US jurisdictions in which bamlanivimab and etesevimab are and are not currently authorized is available on the following FDA website.
• Post-exposure prophylaxis with bamlanivimab and etesevimab is not a substitute for vaccination against COVID-19.
• Bamlanivimab and etesevimab together are not authorized for pre-exposure prophylaxis for prevention of COVID-19.

Important Safety Information
There are limited clinical data available for bamlanivimab and etesevimab together. Serious and unexpected adverse events may occur that have not been previously reported with bamlanivimab and etesevimab together.

Warnings and Precautions
Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions
Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of bamlanivimab with etesevimab. 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, occurring during or up to 24 hours after infusion, have been observed with administration of bamlanivimab and etesevimab together. These reactions may be severe or life threatening. Signs and symptoms of infusion-related reactions may include:

• fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (e.g. atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness, and diaphoresis.

Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs. Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of bamlanivimab with etesevimab under EUA.

Clinical Worsening After Bamlanivimab and Etesevimab Administration
Clinical worsening of COVID-19 after administration of bamlanivimab and etesevimab together has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to bamlanivimab or etesevimab use or were due to progression of COVID-19.

Limitations of Benefit and Potential Risk in Patients with Severe COVID-19
Treatment with bamlanivimab and etesevimab has not been studied in patients hospitalized due to COVID-19. Monoclonal antibodies, such as bamlanivimab and etesevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. See Limitations of Authorized Use.

Adverse Reactions
Adverse reactions observed in those who have received bamlanivimab and etesevimab are anaphylaxis (n=1, 0.07%) and infusion-related reactions (n=16, 1.1%). The most common treatment-emergent adverse events included nausea, dizziness, and pruritis. No treatment-emergent events occurred in more than 1% of participants and rates were comparable to placebo.

Use in Specific Populations
Pregnancy
There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Bamlanivimab and etesevimab together 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 or etesevimab 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.

Healthcare providers should review the Fact Sheet for information on the authorized use of bamlanivimab and etesevimab together 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) for bamlanivimab and etesevimab together.

About bamlanivimab and etesevimab
Bamlanivimab is a recombinant, neutralizing human IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2. It was 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. Lilly scientists rapidly developed the antibody in less than three months after it was discovered by AbCellera and the scientists at the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center. Bamlanivimab was identified from a blood sample taken from one of the first U.S. patients who recovered from COVID-19. 

Etesevimab (LY-CoV016, also known as JS016) is a recombinant fully human monoclonal neutralizing antibody, which specifically binds to the SARS-CoV-2 surface spike protein receptor binding domain with high affinity and can block the binding of the virus to the ACE2 host cell surface receptor. Point mutations were introduced into the native human IgG1 antibody to mitigate effector function. Lilly licensed etesevimab from Junshi Biosciences after it was jointly developed by Junshi Biosciences and the Institute of Microbiology, Chinese Academy of Science (IMCAS). Junshi Biosciences leads development in Greater China, while Lilly leads development in the rest of the world.

Results from a Phase 2/3 study in people recently diagnosed with COVID-19 in the ambulatory setting (BLAZE-1, NCT04427501) were published in the New England Journal of Medicine. Results from a Phase 3 study of bamlanivimab in residents and staff at long-term care facilities (BLAZE-2, NCT04497987) were published in the Journal of American Medical Association (JAMA). A Phase 2 study assessing the efficacy and safety of bamlanivimab alone, and bamlanivimab with other neutralizing antibodies versus placebo for the treatment of symptomatic low-risk COVID-19 in the outpatient setting (BLAZE-4. NCT04634409) has completed enrollment.

About Lilly's COVID-19 Efforts
Lilly is bringing the full force of its scientific and medical expertise to attack the coronavirus pandemic around the world. Existing Lilly medicines are being studied to understand their potential in treating complications of COVID-19, and the company is collaborating with partner companies to discover and develop novel antibody treatments for COVID-19. Click here for resources related to Lilly's COVID-19 efforts.

About Eli Lilly and Company  
Lilly is a global health care leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at www.lilly.com and www.lilly.com/news. P-LLY

Lilly Cautionary Statement Regarding Forward-Looking Statements 
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016) together as a potential therapy for patients with COVID-19, as well as bamlanivimab (LY-CoV555) alone, the supply, distribution and contracts with the governments relating to these therapies, and Lilly's development plans, and reflects Lilly's current beliefs and expectations. However, as with any such undertaking, there are substantial risks and uncertainties in the process of drug research, development and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date, that bamlanivimab and etesevimab together or any other therapy will prove to be safe and effective treatments or successful preventative therapies for COVID-19, that bamlanivimab and etesevimab together or any other therapy will receive regulatory approvals or additional authorizations, that patients will volunteer to participate in clinical trials or achieve positive outcomes, that Lilly will obtain any additional purchase orders or supply contracts, or that Lilly can provide an adequate supply of bamlanivimab and etesevimab together or any other therapy in all circumstances. For a further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, please see Lilly's most recent Forms 10-K and 10-Q filed with the U.S. Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.  

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