Bamlanivimab

BAMLANIVIMAB- bamlanivimab injection, solution
Eli Lilly and Company

AUTHORIZED USE

TREATMENT

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to permit the emergency use of the unapproved products bamlanivimab and etesevimab administered together for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients, including neonates, 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

  • Bamlanivimab and etesevimab are not authorized for treatment of mild to moderate COVID-19 in geographic regions where infection is likely to have been caused by a non-susceptible SARS-CoV-2 variant based on available information including variant susceptibility to these drugs and regional variant frequency.
    • FDA’s determination and any updates will be available at: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs.1
  • Bamlanivimab and etesevimab are not authorized for use in patients 2 years and older who are hospitalized due to COVID-19.2
  • Bamlanivimab and etesevimab are not authorized for use in patients, regardless of age, who:
    • require oxygen therapy and/or respiratory support due to COVID-19, OR
    • require an increase in baseline oxygen flow rate and/or respiratory support due to COVID-19 and are on chronic oxygen therapy and/or respiratory support due to underlying non-COVID-19 related comorbidity.
  • 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.

POST-EXPOSURE PROPHYLAXIS

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to permit the emergency use of the unapproved products bamlanivimab and etesevimab administered together in adults and pediatric individuals, including neonates, for post-exposure prophylaxis of COVID-19 in individuals who are at high risk of progression to severe COVID-19, including hospitalization or death, and are:

  • not fully vaccinated 3 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 medications 4) 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)5 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) [see Limitations of Authorized Use (1.2)].

Limitations of Authorized Use

  • Bamlanivimab and etesevimab are not authorized for post-exposure prophylaxis of COVID-19 in geographic regions where exposure is likely to have been to a non-susceptible SARS-CoV-2 variant, based on available information including variant susceptibility to these drugs and regional variant frequency.
    • FDA’s determination and any updates will be available at: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs.1
  • Post-exposure prophylaxis with bamlanivimab and etesevimab is not a substitute for vaccination against COVID-19.
  • Bamlanivimab and etesevimab are not authorized for pre-exposure prophylaxis for prevention of COVID-19.

1
FDA will monitor conditions to determine whether use in a geographic region is consistent with this scope of authorization, referring to available information, including information on variant susceptibility [see Microbiology/Resistance Information (15)] , and CDC regional variant frequency data available at: https://covid.cdc.gov/covid-data-tracker/#variant-proportions.
2
The reasons for hospital admission may be different and the threshold for hospital admission may be lower for neonates, young infants and toddlers with COVID-19 compared to older children and adults. The authorization allows for young children (i.e., birth to 2 years of age) who are hospitalized with mild to moderate COVID-19 at the time of treatment to receive bamlanivimab and etesevimab.
3
Individuals are considered to be fully vaccinated 2 weeks after their second vaccine dose in a 2-dose series (such as the Pfizer or Moderna vaccines), or 2 weeks after a single-dose vaccine (such as Johnson & Johnson’s Janssen vaccine). See this website for more details: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated.html#vaccinated.
4
See this website for more details: https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/fully-vaccinated-people.html.
5
Close contact with an infected individual is defined as: being within 6 feet for a total of 15 minutes or more, providing care at home to someone who is sick, having direct physical contact with the person (hugging or kissing, for example), sharing eating or drinking utensils, or being exposed to respiratory droplets from an infected person (sneezing or coughing, for example). See this website for additional details: https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/quarantine.html.

RECENT MAJOR CHANGES

  • Limitations of Authorized Use– updated Limitations of Authorized Use for treatment and post-exposure prophylaxis.
Revised 01/2022
  • Limitations of Authorized Use (Section 1 and Box)– removal of the Limitations of Authorized Use related to resistant variants and modification of SARS-CoV-2 viral variant section of the Box.
Revised 12/2021
  • Antiviral Resistance (Box and Section 15)– addition of information on susceptibility of SARS-CoV-2 variants to bamlanivimab and etesevimab (Table 5 and Table 6) and updates based on latest viral surveillance report and additional sequencing data from Phase 3 study PYAB.
Revised 12/2021, 08/2021, 05/2021, and 03/2021
Revised 12/2021
  • How Supplied/Storage and Handling (Section 19)– addition of information related to the extension of expiry date of bamlanivimab and etesevimab.
Revised 12/2021
  • Authorized Use (Box and Section 1)– addition of new indication for post-exposure prophylaxis of COVID-19.
Revised 09/2021
  • Clinical Trial Results and Supporting Data for EUA, Post-Exposure Prophylaxis of COVID-19 (BLAZE-2) (Section 18.2)– addition of Phase 3 data for the authorized use.
Revised 09/2021
  • Authorized Use (Box and Section 1)– expanded the definition of progression of severe COVID-19 to include death.
Revised 08/2021
  • Limitations of Authorized Use (Section 1)– change to authorized use related to the combined frequency of SARS-CoV-2 variants that are resistant to bamlanivimab and etesevimab.
Revised 08/2021
  • Warnings: Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions (Section 5.1)– addition of vasovagal reactions.
Revised 08/2021
  • Warnings: Clinical Worsening After Bamlanivimab and Etesevimab Administration (Section 5.2)– updated to include administration with both antibodies.
Revised 08/2021
  • Definition of High Risk for Disease Progression (Box and Section 2.1)– definition has been expanded to include additional medical conditions and other factors.
Revised 05/2021
  • Dosage and Administration, Dosage (Section 2.2)– removal of rationale for authorized dose because Phase 3 data have confirmed the authorized dose.
Revised 05/2021
  • Overall Safety Summary, Clinical Trials Experience (Section 6.1)– updated to integrated clinical trial safety analyses focused on adverse reactions and most common treatment-emergent adverse events.
Revised 05/2021
  • Clinical Trial Results and Supporting Data for EUA, Mild to Moderate COVID-19 (BLAZE-1) (Section 18.1)– addition of Phase 3 data for the authorized dose.
Revised 05/2021

Bamlanivimab and etesevimab have been authorized by FDA for the emergency uses described above.

Bamlanivimab and etesevimab are not FDA-approved for these uses.

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

Treatment

This EUA is for the use of the unapproved products bamlanivimab and etesevimab administered together for the treatment of mild to moderate COVID-19 in adults and pediatric patients, including neonates, 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 [see Limitations of Authorized Use (1.1)].

For treatment of COVID-19, bamlanivimab and etesevimab should be administered together as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 10 days of symptom onset.

Post-Exposure Prophylaxis

This EUA is for the use of the unapproved products bamlanivimab and etesevimab administered together in adults and pediatric individuals, including neonates, for post-exposure prophylaxis of COVID-19 in individuals who are at high risk for progression to severe COVID-19, including hospitalization or death, and are:

  • not fully vaccinated 3 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 medications 3 ) 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)5 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) [see Limitations of Authorized Use (1.2)] .

For post-exposure prophylaxis, bamlanivimab and etesevimab should be administered together as soon as possible following exposure to SARS-CoV-2.

Criteria for Identifying High Risk Individuals

The following medical conditions or other factors may place adults and pediatric patients, including neonates, at higher risk for progression to severe COVID-19:

  • Older age (for example age ≥65 years of age)
  • <1 year old
  • Obesity or being overweight
  • Pregnancy
  • Chronic kidney disease
  • Diabetes
  • Immunosuppressive disease or immunosuppressive treatment
  • Cardiovascular disease (including congenital heart disease) or hypertension
  • Chronic lung diseases (for example, chronic obstructive pulmonary disease, asthma [moderate-to-severe], interstitial lung disease, cystic fibrosis and pulmonary hypertension)
  • Sickle cell disease
  • Neurodevelopmental disorders (for example, cerebral palsy) or other conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies)
  • Having a medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19))

Other medical conditions or factors (for example, race or ethnicity) may also place individual patients at high risk for progression to severe COVID-19 and authorization of bamlanivimab and etesevimab under the EUA is not limited to the medical conditions or factors listed above. For additional information on medical conditions and factors associated with increased risk for progression to severe COVID-19, see the CDC website: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Healthcare providers should consider the benefit-risk for an individual patient.

Under this EUA, bamlanivimab and etesevimab must be administered together by intravenous (IV) infusion only.

Treatment Dosage

  • The authorized dosage for adults (18 years and older) and pediatric patients (<18 years and weighing at least 40 kg) is 700 mg bamlanivimab and 1,400 mg of etesevimab administered together as a single intravenous (IV) infusion [see Dosage and Administration (2.2, 2.4) and Clinical Trial Results and Supporting Data for EUA (18.1)]. The authorized dosage for pediatric patients weighing less than 40 kg will vary depending on weight [see Dosage and Administration (2.2, 2.4)]. Given the similar course of COVID-19, the safety and efficacy of bamlanivimab and etesevimab in younger pediatric patients, including neonates, is supported by safety and efficacy data in adolescents and adults, together with additional pharmacokinetic and safety data from the clinical trial in pediatric patients. The recommended dosing regimen for pediatric patients ≤12 kg is based on pharmacokinetic modeling and simulation [see Clinical Pharmacology (14.3)]. The youngest participant in the pediatric clinical trial was 10 months of age and weighed 8.6 kg [see Clinical Trials and Supporting Data for EUA (18.1)].

Post-Exposure Prophylaxis Dosage

  • The authorized dosage for adults (18 years and older) and pediatric individuals (<18 years and weighing at least 40 kg) is 700 mg bamlanivimab and 1,400 mg of etesevimab administered together as a single intravenous (IV) infusion [see Dosage and Administration (2.2, 2.4)]. The authorized dosage for pediatric individuals weighing less than 40 kg will vary depending on weight [see Dosage and Administration (2.2, 2.4)].
  • The authorized dosage is based on the totality of the scientific evidence including clinical pharmacology data and clinical trial data [see Clinical Pharmacology (14.2) and Clinical Trial Results and Supporting Data for EUA (18.2)]. The recommended dosing regimen for pediatric patients ≤12 kg is predicted based on pharmacokinetic modeling and simulation [see Clinical Pharmacology (14.3)].
  • The clinical data for post-exposure prophylaxis is based on data generated in the Phase 3 study BLAZE-2. While this study only evaluated dosing with bamlanivimab alone, it is reasonable to expect that bamlanivimab and etesevimab together may be safe and effective for post-exposure prophylaxis based on:
    • Phase 3 data from BLAZE-1 demonstrated treatment of COVID-19 with bamlanivimab and etesevimab together showed a statistically significant reduction in progression of severe COVID-19, including hospitalization or death [see Clinical Trial Results and Supporting Data for EUA (18.1)].
    • Nonclinical and clinical data support that bamlanivimab and etesevimab together will provide an advantage over bamlanivimab alone against certain SARS-CoV-2 viral variants [see Microbiology/Resistance Information (15)].
  • Use of bamlanivimab and etesevimab together for post-exposure prophylaxis in subjects who meet high-risk criteria is based on a subgroup analysis of high-risk individuals enrolled in BLAZE-2 [see Clinical Trial Results and Supporting Data for EUA (18.2)].
  • Given the similar course of COVID-19, the safety and efficacy of bamlanivimab and etesevimab in younger pediatric patients, including neonates, is supported by safety and efficacy data in adolescents and adults, together with additional pharmacokinetic and safety data from the clinical trial in pediatric patients studying bamlanivimab and etesevimab for the treatment of mild to moderate COVID-19. Children were not enrolled in the post-exposure prophylaxis trial, BLAZE-2.

Intravenous Infusion:

  • Bamlanivimab and etesevimab are both available as solutions in separate vials and must be combined prior to administration.
  • Administer bamlanivimab and etesevimab together as a single intravenous (IV) infusion via pump or gravity [see Table 1 and Table 2 and Dosage and Administration (2.4)].
  • Clinically monitor patients during administration and observe patients for at least 1 hour after infusion is complete.
  • Repeat dosing of bamlanivimab and etesevimab has not been evaluated.

Bamlanivimab and etesevimab may only be administered in settings in which health care providers have immediate access to medications to treat a severe infusion reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS), as necessary.

Health care providers must submit a report on all medication errors and ALL SERIOUS ADVERSE EVENTS potentially related to bamlanivimab and etesevimab. See Sections 8 and 9 of the Full EUA Prescribing Information for reporting instructions below.

Patients treated with bamlanivimab and etesevimab together should continue to self-isolate and use infection control measures (e.g., wear mask, isolate, social distance, avoid sharing personal items, clean and disinfect “high touch” surfaces, and frequent handwashing) according to CDC guidelines.

The authorized dosage may be updated as additional data from clinical trials becomes available.

For information on clinical trials that are testing the use of bamlanivimab and etesevimab in COVID-19, please see www.clinicaltrials.gov.

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