Lilly (LLY) requests revocation of EUA for bamlanivimab alone to complete transition to bamlanivimab and etesevimab together for treatment of COVID-19 in the U.S.

Eli Lilly and Company (NYSE: LLY) has requested the U.S. Food and Drug Administration (FDA) revoke the Emergency Use Authorization (EUA) for bamlanivimab (LY-CoV555) 700 mg alone. Lilly made this request due to the evolving variant landscape in the U.S. and the full availability of bamlanivimab and etesevimab together. This request is not due to any new safety concern.

This final step in Lilly's transition to only supply bamlanivimab and etesevimab for administration together in the U.S. for the treatment of COVID-19 – as planned with the FDA – follows the modification of contracts with the U.S. government to ensure adequate supply of etesevimab to be used together with bamlanivimab.

All sites in the U.S. now have access to obtain doses of etesevimab for administration with bamlanivimab—which together neutralize more of the emerging COVID-19 variants in the U.S. than bamlanivimab alone, including the rapidly growing B.1.427/B.1.429 California strain that currently accounts for 50 percent of the virus in California and over 10 percent across a number of additional states. In the U.S., bamlanivimab alone should no longer be administered. However, sites of care should not dispose of bamlanivimab supply; instead, they should order etesevimab to pair with it.

"Lilly moved quickly to make bamlanivimab alone available as a potentially lifesaving medicine at a time when Americans were hardest hit by COVID-19," said Daniel Skovronsky, M.D., Ph.D., Lilly's chief scientific officer and president of Lilly Research Laboratories. "With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together."

Lilly's bamlanivimab was the first neutralizing monoclonal antibody to receive emergency use authorization from the FDA as a treatment for mild to moderate COVID-19 — providing a valuable treatment at a time when cases were at their highest in the U.S. More than 400,000 patients have been treated with bamlanivimab – more than any other neutralizing antibody – potentially preventing more than 20,000 hospitalizations and at least 10,000 deaths during the worst of the pandemic in the U.S.

Lilly developed bamlanivimab and etesevimab for administration together to meet the potential challenge of treatment-resistant variants likely to resist treatment with either monoclonal antibody used alone. Due to the rapidly evolving and geographically diverse nature of the SARS-CoV-2 virus, continued scientific innovation remains critical to develop additional treatments. Lilly remains committed to developing complementary neutralizing antibodies to address potential SARS-CoV-2 variants that may arise in the future.

Bamlanivimab and/or bamlanivimab administered with etesevimab are authorized under special pathways in 20 countries outside the U.S. spanning four continents. Both bamlanivimab alone and bamlanivimab and etesevimab together retain the neutralization effects against the vast majority of variants, including the UK (B.1.1.7.) variant, present in these other countries and remain an important treatment option. The degree of neutralization of the virus does not necessarily equate to improved clinical outcomes.

Lilly is not requesting the withdrawal of emergency authorization for bamlanivimab alone in any other jurisdiction at this time. However, its use together with etesevimab, where authorized and available, is preferred over bamlanivimab alone. Lilly, in collaboration with Amgen, expects to manufacture sufficient supply of bamlanivimab and etesevimab together to meet global supply needs. Going forward, Lilly will submit only bamlanivimab administered with etesevimab together for authorization globally with a full transition expected by June 2021.

For more information about the use of bamlanivimab and etesevimab together for the treatment of mild to moderate COVID-19 in high-risk patients under the FDA's emergency use authorization, contact Lilly's 24-hour support line at 1-855-LillyC19 (1-855-545-5921). Patients and physicians can visit covid.infusioncenter.org or the HHS Therapeutics Distribution locator to find a potential treatment location.

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Important Information about bamlanivimab and etesevimab togetherBamlanivimab and etesevimab together have 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 of COVID-19.

Bamlanivimab and etesevimab together are authorized under Emergency Use Authorization 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.

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.

Authorized Use and Important Safety InformationBamlanivimab and etesevimab together are 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 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.

Important Safety InformationThere 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.

Hypersensitivity Including Anaphylaxis and Infusion-Related ReactionsSerious hypersensitivity reactions, including anaphylaxis, have been observed with administration of bamlanivimab with and without 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 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.

If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care.

Clinical Worsening After Bamlanivimab AdministrationClinical worsening of COVID-19 after administration of bamlanivimab 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 use or were due to progression of COVID-19.

Limitations of Benefit and Potential Risk in Patients with Severe COVID-19Treatment 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. See Limitations of Authorized Use.

Adverse EventsBased on Phase 2 data from BLAZE-1, nausea was the most commonly reported adverse event, reported by 4% of subjects in both bamlanivimab and etesevimab together and placebo groups. Pruritus and pyrexia were more frequently reported from subjects treated with both bamlanivimab and etesevimab (2% and 1%) compared to placebo (1% and 0%, respectively).

Based on Phase 3 data from BLAZE-1, the most common adverse events were nausea, dizziness, and rash. These events each occurred in 1% of subjects treated with bamlanivimab and etesevimab together and in 1% of placebo subjects.

Use in Specific PopulationsPregnancyThere are insufficient data on the use of bamlanivimab and etesevimab together during pregnancy. Bamlanivimab and etesevimab together should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus.

BreastfeedingThere 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.

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