Bamlanivimab (Page 7 of 12)

9 OTHER REPORTING REQUIREMENTS

  • Healthcare facilities and providers must report therapeutics information and utilization data through HHS Protect, Teletracking or National Healthcare Safety Network (NHSN) as directed by the U.S. Department of Health and Human Services.
  • In addition, please provide a copy of all FDA MedWatch forms to:
    Eli Lilly and Company, Global Patient Safety
    Fax: 1-317-277-0853
    E-mail: mailindata_gsmtindy@lilly.comOr call Eli Lilly and Company at 1-855-LillyC19 (1-855-545-5921) to report adverse events.

10 DRUG INTERACTIONS

Bamlanivimab and etesevimab are not renally excreted or metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are renally excreted or that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

11 USE IN SPECIFIC POPULATIONS

11.1 Pregnancy

Risk Summary

There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Bamlanivimab and etesevimab should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus. There are maternal and fetal risks associated with untreated COVID-19 in pregnancy (see Clinical Considerations).

Nonclinical reproductive toxicity studies have not been performed with bamlanivimab or etesevimab. In tissue cross reactivity studies using human fetal tissues, no binding of clinical concern was detected for etesevimab or bamlanivimab. Human immunoglobulin G1 (IgG1) antibodies are known to cross the placental barrier; therefore, bamlanivimab and etesevimab have the potential to be transferred from the mother to the developing fetus. It is unknown whether the potential transfer of bamlanivimab or etesevimab provides any treatment benefit or risk to the developing fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo-Fetal Risk

COVID-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death.

11.2 Lactation

Risk Summary

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. Maternal IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for bamlanivimab and etesevimab and any potential adverse effects on the breastfed child from bamlanivimab and etesevimab or from the underlying maternal condition. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

11.3 Pediatric Use

Bamlanivimab and etesevimab administered together are authorized for the treatment of mild to moderate COVID-19 and post-exposure prophylaxis for prevention of COVID-19 in pediatric patients, including neonates [see Authorized Use (1)]. Given the similar course of COVID-19, the authorization of bamlanivimab and etesevimab for treatment and post-exposure prophylaxis 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.

Use of bamlanivimab and etesevimab in pediatric patients is based on analyses of data from BLAZE-1 in subjects aged 10 months to 18 years of age [see Clinical Pharmacology (14.3) and Clinical Trials and Supporting Data for EUA (18.1)]. No dosage adjustment is recommended in pediatric patients 12-18 years of age who weigh at least 40 kg. Pediatric patients weighing less than 40 kg should be dosed on the basis of body weight [see Dosage and Administration (2.2, 2.4)]. The recommended dosing regimen for pediatric patients ≤12 kg is predicted based on pharmacokinetic modeling and simulation [see Clinical Pharmacology (14.3)]. The youngest participant in the pediatric clinical trial for treatment was 10 months of age and weighed 8.6 kg [see Clinical Trials and Supporting Data for EUA (18.1)]. Safety in pediatric patients was similar to what was observed in adults [see Clinical Trial Experience (6.1)]. Children were not enrolled in the post-exposure prophylaxis trial, BLAZE-2 [see Clinical Trials and Supporting Data for EUA (18.2)].

11.4 Geriatric Use

Of the 1141 patients receiving bamlanivimab and etesevimab in BLAZE-1, 30% were 65 years of age and older and 10% were 75 years of age and older. Based on population PK analyses, there is no difference in PK of bamlanivimab or etesevimab in geriatric patients compared to younger patients [see Clinical Trial Results and Supporting Data for EUA (18.1)].

11.5 Renal Impairment

Bamlanivimab and etesevimab are not eliminated intact in the urine, thus renal impairment is not expected to affect the exposure of bamlanivimab or etesevimab.

11.6 Hepatic Impairment

Based on population PK analysis, there is no difference in PK of bamlanivimab or etesevimab in patients with mild hepatic impairment compared to patients with normal hepatic function. Bamlanivimab and etesevimab have not been studied in patients with moderate or severe hepatic impairment.

11.7 Other Specific Populations

Based on population PK analysis, the PK of bamlanivimab and etesevimab was not affected by sex, race, or disease severity. Body weight had no clinically relevant effect on the PK of bamlanivimab and etesevimab in adults with COVID-19 over the body weight range of 41 kg to 173 kg.

12 OVERDOSAGE

Doses up to 7,000 mg of bamlanivimab (10 times the authorized dose of bamlanivimab for adults [≥18 years] and pediatric patients [<18 years weighing at least 40 kg]) or 7,000 mg of etesevimab (5 times the authorized dose of etesevimab for adults [≥18 years] and pediatric patients [<18 years weighing at least 40 kg]) have been administered in clinical trials without dose-limiting toxicity. Treatment of overdose with bamlanivimab and etesevimab should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with either bamlanivimab or etesevimab.

13 DESCRIPTION

Bamlanivimab

Bamlanivimab is a human immunoglobulin G-1 (IgG1 variant) monoclonal antibody consisting of 2 identical light chain polypeptides composed of 214 amino acids each and 2 identical heavy chain polypeptides composed of 455 amino acids produced by a Chinese Hamster Ovary (CHO) cell line and molecular weight of 146 kDa.

Bamlanivimab injection is a sterile, preservative-free, clear to opalescent and colorless to slightly yellow to slightly brown solution in a vial for intravenous infusion.

Each mL contains 35 mg of bamlanivimab, and L-histidine (0.4 mg), L-histidine hydrochloride monohydrate (0.6 mg), sodium chloride (2.9 mg), sucrose (60 mg), polysorbate 80 (0.5 mg), and Water for Injection. The bamlanivimab solution has a pH range of 5.5-6.5.

Etesevimab

Etesevimab is a human IgG1 variant monoclonal antibody (mAb) consisting of 2 identical light chain polypeptides composed of 216 amino acids each and 2 identical heavy chain polypeptides composed of 449 amino acids produced by a Chinese Hamster Ovary (CHO) cell line and molecular weight of 145 kDa.

Etesevimab injection is a sterile, preservative-free, clear to opalescent and colorless to slightly yellow to slightly brown solution in a vial for intravenous infusion.

Each mL contains 35 mg of etesevimab, L-histidine (1.55 mg), L-histidine hydrochloride monohydrate (2.10 mg), sucrose (80.4 mg), polysorbate 80 (0.5 mg), and Water for injection. The etesevimab solution has a pH range of 5.5.-6.5.

14 CLINICAL PHARMACOLOGY

14.1 Mechanism of Action

Bamlanivimab is a recombinant neutralizing human IgG1ϰ monoclonal antibody (mAb) to the spike protein of SARS-CoV-2 and is unmodified in the Fc region. Bamlanivimab binds the spike protein with a dissociation constant KD = 0.071 nM and blocks spike protein attachment to the human ACE2 receptor with an IC50 value of 0.17 nM (0.025 μg/mL).

Etesevimab is a recombinant neutralizing human IgG1ϰ mAb to the spike protein of SARS-CoV-2, with amino acid substitutions in the Fc region (L234A, L235A) to reduce effector function. Etesevimab binds the spike protein with a dissociation constant KD = 6.45 nM and blocks spike protein attachment to the human ACE2 receptor with an IC50 value of 0.32 nM (0.046 μg/mL).

Bamlanivimab and etesevimab bind to different but overlapping epitopes in the receptor binding domain (RBD) of the S-protein. Using both antibodies together is expected to reduce the risk of viral resistance.

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