BLAZE-1 is an ongoing, randomized, double-blind, placebo-controlled, Phase 2 study
The data supporting bamlanivimab's authorization are based on interim data from one Phase 2 trial of 465 ambulatory (non-hospitalized) subjects with COVID-19. One arm of this study is designed to evaluate the efficacy and safety of bamlanivimab alone in participants with early mild to moderate COVID-19 illness. This study began in June 2020 with the primary endpoint reached in September 2020 and the completion of the study is estimated to be in January 2021.
- Change from baseline to Day 11 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral load
- Proportion of subjects with COVID-19-related hospitalizations or emergency room visits within 28 days of treatment
- Median time to symptom improvement
- 18 years or older
- Currently NOT hospitalized
- One or more mild or moderate COVID-19 symptoms: Fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, or shortness of breath with exertion
- Confirmed viral infection no more than 3 days prior to starting the drug infusion
- Men or non-pregnant women who agree to contraceptive requirements
- Participants are greater than or equal to (≥) 65 years of age at the time of randomization OR have a body mass index (BMI) ≥35 OR are ≥55 years of age and have a BMI ≥30 and have a history of myocardial infarction or stroke
- Oxygen saturation (SpO2) ≤93% on room air at sea level or ratio of arterial oxygen partial pressure (PaO2 in millimeters of mercury) to fractional inspired oxygen (FiO2) <300, respiratory rate greater ≥30 per minute, heart rate ≥125 per minute
- Require mechanical ventilation or anticipated impending need for mechanical ventilation
- Have hemodynamic instability requiring use of vasopressors within 24 hours of randomization
- Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking intervention
- History of a positive SARS-CoV-2 test prior to the one serving as eligibility for this study
- Received an investigational intervention for SARS-CoV-2 prophylaxis within 30 days before dosing
- Received treatment with a SARS-CoV-2 specific monoclonal antibody, COVID-19 plasma treatment, or SARS-CoV-2 vaccine
Baseline demographics and disease characteristics in the safety population
At baseline, median age was 45 years (with 12% of subjects aged 65 or older); 55% of subjects were female, 88% were White, 44% were Hispanic or Latino, and 6% were Black; 44% of subjects were considered high risk.
The baseline demographics and disease characteristics were well balanced across bamlanivimab and placebo treatment groups.
When administered as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset, bamlanivimab may reduce viral load, symptoms, and risk of hospitalizations and emergency room visits associated with COVID-19 illness.
COVID-19-related hospitalization or ER visits
Initial data from a BLAZE-1 Phase 2 placebo controlled trial evaluating the safety and efficacy of bamlanivimab versus placebo in 465 adult patients with COVID-19, showed a lower proportion of patients who progress to COVID-19-related hospitalization or emergency room visits for bamlanivimab-treated versus placebo-treated patients.
Events of hospitalization or emergency room visits within 28 days after treatment
|Placebo||Patients Treated: 156||Events: 9||Rate: 5.8%|
|bamlanivimab 700 mg||Patients Treated: 101||Events: 1||Rate: 1.0%|
|bamlanivimab 2800 mg||Patients Treated: 107||Events: 2||Rate: 1.9%|
|bamlanivimab 7000 mg||Patients Treated: 101||Events: 2||Rate: 2.0%|
|All bamlanivimab doses||Patients Treated: 309||Events: 5||Rate: 1.6%|
- Bamlanivimab is not authorized at doses of 2,800 mg and 7,000 mg.
COVID-19-related hospitalization or ER visits in patients at higher risk
Most hospitalization occurred in patients with underlying risk factors (age or BMI), suggesting a more pronounced treatment effect for patients in these higher-risk groups. The absolute risk reduction is greater in patients of older age (65 or older) or higher BMI (35 or higher), hence at higher risk of hospitalization.
Events of hospitalization or emergency room visits within 28 days after treatment for patients at higher risk of hospitalizations
|Placebo||Patients Treated: 69||Events: 7||Rate: 10%|
|bamlanivimab 700 mg||Patients Treated: 46||Events: 1||Rate: 2%|
|bamlanivimab 2800 mg||Patients Treated: 46||Events: 1||Rate: 2%|
|bamlanivimab 7000 mg||Patients Treated: 44||Events: 2||Rate: 5%|
|All bamlanivimab doses||Patients Treated: 136||Events: 4||Rate: 3%|
The median time to symptom improvement for bamlanivimab-treated patients was 6 days from receiving treatment, as compared with 8 days for placebo-treated patients.
There are limited clinical data available for bamlanivimab. Serious and unexpected adverse events may occur that have not been previously reported with bamlanivimab use.
Based on data from 309 bamlanivimab-treated subjects followed for at least 28 days after treatment, adverse events occurred in 23% bamlanivimab-treated subjects and 26% of placebo-treated subjects. Serious adverse events occurred in 1 placebo-treated subject (1%) and in no bamlanivimab-treated subjects.
The most commonly reported adverse event was nausea. The table below shows adverse events reported in at least 1% of patients in any treatment group. Bamlanivimab is not authorized at doses of 2,800 mg or 7,000 mg.
Treatment-emergent Adverse Events Reported in at Least 1% of All Subjects in BLAZE-1
|Preferred term||Placebo N=156 %||Bamlanivimab 700 N=101 %||Bamlanivimab 2,800 N=107 %||Bamlanivimab 7,000 N=101 %||Bamlanivimab N=101 %|
|Nausea||Placebo N=156 %: 4%||Bamlanivimab 700 N=101 %: 3%||Bamlanivimab 2,800 N=107 %: 4%||Bamlanivimab 7,000 N=101 %: 5%||Bamlanivimab N=101 %: 4%|
|Diarrhea||Placebo N=156 %: 5%||Bamlanivimab 700 N=101 %: 1%||Bamlanivimab 2,800 N=107 %: 2%||Bamlanivimab 7,000 N=101 %: 7%||Bamlanivimab N=101 %: 3%|
|Dizziness||Placebo N=156 %: 2%||Bamlanivimab 700 N=101 %: 3%||Bamlanivimab 2,800 N=107 %: 3%||Bamlanivimab 7,000 N=101 %: 3%||Bamlanivimab N=101 %: 3%|
|Headache||Placebo N=156 %: 2%||Bamlanivimab 700 N=101 %: 3%||Bamlanivimab 2,800 N=107 %: 2%||Bamlanivimab 7,000 N=101 %: 0%||Bamlanivimab N=101 %: 2%|
|Pruritus||Placebo N=156 %: 1%||Bamlanivimab 700 N=101 %: 2%||Bamlanivimab 2,800 N=107 %: 3%||Bamlanivimab 7,000 N=101 %: 0%||Bamlanivimab N=101 %: 2%|
|Vomiting||Placebo N=156 %: 3%||Bamlanivimab 700 N=101 %: 1%||Bamlanivimab 2,800 N=107 %: 3%||Bamlanivimab 7,000 N=101 %: 1%||Bamlanivimab N=101 %: 2%|
Hypersensitivity Including Anaphylaxis and Infusion-related Reactions:
Across ongoing blinded clinical trials, a case of anaphylaxis and other cases of serious infusion-related reactions were reported with infusion of bamlanivimab. The infusions were stopped. All reactions required treatment, one required epinephrine. All events resolved.
Immediate non-serious hypersensitivity events were noted for 2% of bamlanivimab-treated subjects and 1% of placebo-treated subjects in BLAZE-1. Reported events of pruritus, flushing and hypersensitivity were mild with one case of face swelling which was moderate. All events resolved.
In order to mitigate the risks of using this unapproved product under the EUA and to optimize the potential benefit of bamlanivimab, the following items are required. Use of bamlanivimab under this EUA is limited to the following (all requirements must be met):
- 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.
As the healthcare provider, communicate to your patient or parent/caregiver information
consistent with the Fact Sheet for Patients, Parents and
Caregivers (English) or Fact Sheet for Patients, Parents and Caregivers (Spanish) prior to the patient
receiving bamlanivimab. Healthcare providers (to the extent practicable given the
circumstances of the emergency) must document in the patient’s medical record that the
patient/caregiver has been:
- Given the Fact Sheet for Patients, Parents and Caregivers,
- Informed of alternatives to receiving authorized bamlanivimab, and
- Informed that bamlanivimab is an unapproved drug that is authorized for use under this Emergency Use Authorization.
- The prescribing healthcare provider and/or the provider’s designee are/is to provide responses to requests from FDA for information about adverse events and medication errors following receipt of bamlanivimab.
- The prescribing healthcare provider and/or the provider’s designee are/is responsible for reporting medication errors and adverse events (death, serious adverse events*) occurring during bamlanivimab treatment within 7 calendar days from the onset of the event. The reports should include unique identifiers and the words “Bamlanivimab use for the treatment of COVID-19 under an Emergency Use Authorization (EUA)” in the description section of the report.
Submit adverse event reports to FDA MedWatch using one of the following methods:
- Complete and submit the report online, or
- By using a postage-paid Form FDA 3500 (available here) and returning by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787), or by fax (1-800-FDA-0178), or
- Call 1-800-FDA-1088 to request a reporting form
- Submitted reports should include in the field name, “Describe Event, Problem, or Product Use/Medication Error” and the statement “Bamlanivimab use for treatment of COVID-19”
*Serious Adverse Events are defined as:
- a life-threatening adverse event;
- inpatient hospitalization or prolongation of existing hospitalization;
- a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;
- a congenital anomaly/birth defect;
- a medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly.
5. OTHER REPORTING REQUIREMENTS
In addition, please provide a copy of all FDA MedWatch forms to:
Eli Lilly and Company, Global Patient Safety