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bebtelovimab

175mg

HCP Fact Sheet | Patient & Caregiver Fact Sheet | FDA Authorization Letter

This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.

What are the safety and efficacy results of bebtelovimab from BLAZE-4?

Bebtelovimab reduces viral load and decreases time to symptom resolution in both low- and high-risk patients with mild to moderate COVID-19. Adverse reactions in patients treated with bebtelovimab include rash, pruritis, and infusion-related reactions.

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Bebtelovimab Emergency Use Authorization

Bebtelovimab has not been approved, but has only been authorized for emergency use by Food and Drug Administration (FDA) for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of bebtelovimab under Section 564(b)(1)(C) of the Act, 21 U.S.C. 360bbb-3, unless the authorization is terminated or revoked sooner.1,2

Bebtelovimab is 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, and
for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate.1,2

For information on the authorized use of bebtelovimab and mandatory requirements under the emergency use authorization (EUA), please review the FDA Letter of Authorization, Fact Sheet for Healthcare Providers, and Fact Sheet for Patients/Caregivers at www.LillyAntibody.com/bebtelovimab. 1,2

Bebtelovimab in BLAZE-4 Clinical Trial

Clinical Trial Overview

BLAZE-4 is a phase 2, randomized, single-dose clinical trial evaluating treatment of non-hospitalized patients with mild-to-moderate COVID-19.1

Bebtelovimab was among the treatment interventions studied in BLAZE-4. It was evaluated alone and together with bamlanivimab and etesevimab in

low-risk adults (ie, those not at high-risk to progress to severe COVID-19) and compared to a placebo control arm, and
high-risk adults and pediatric patients (12 years of age and older weighing at least 40 kg) who all received open-label active treatments.1

Because there are other therapeutic options available, a placebo control could not be used to treat high-risk patients.1

Additional study design details are described in Clinical Trial Overview of the Phase 2 BLAZE-4 Bebtelovimab Treatment Arms.

Clinical Trial Overview of the Phase 2 BLAZE-4 Bebtelovimab Treatment Arms1,3,4
	BLAZE-4 (NCT04634409) Phase 2 bebtelovimab treatment arms
Design	Phase 2, randomized, single-dose study in patients with mild-to-moderate COVID-19.
Locations	United States
Treatment arms	Placebo-controlled portion (low-risk patients; treatment arms 9-11) bamlanivimab 700 mg, etesevimab 1400 mg, and bebtelovimab 175 mg together (n=127) bebtelovimab 175 mg alone (n=125) placebo (n=128)
	Open-label randomized portion (high-risk patients; treatment arms 12-13)a bamlanivimab 700 mg, etesevimab 1400 mg, and bebtelovimab 175 mg together (n=50) bebtelovimab 175 mg alone (n=100)
	Open-label non-randomized portion (high-risk patients; treatment arm 14)a bamlanivimab 700 mg, etesevimab 1400 mg, and bebtelovimab 175 mg together (n=176)
Key inclusion criteriab	18 to 65 years old currently NOT hospitalized 1 or more mild or moderate COVID-19 symptoms: fever, cough, sore throat, malaise, headache, muscle pain, GI symptoms, or SOB with exertion, nasal congestion or runny nose, new loss of smell, chills sample collection for first positive SARS-CoV-2 test ≤3 days prior to start of the infusion men or non-pregnant women who agree to contraceptive requirements
Key exclusion criteriab	SpO2 ≤93% on room air at sea level or PaO2/FiO2 <300, respiratory rate ≥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 have any co-morbidity requiring surgery within <7 days, or that is considered life-threatening within 29 days 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 or COVID-19 plasma treatment are pregnant or breast feeding body weight < 40 kg
Primary outcomes	% of patients with SARS-CoV-2 Viral Load Greater than 5.27 at Day 7 (placebo-controlled) characterization of the bebtelovimab safety profile including adverse events and serious adverse events (open-label)
Selected key secondary outcomes	% of patients who experience COVID-related hospitalizationc or death by any cause through day 29 Mean change in viral load from baseline to Day 3, 5, and 7 Median time to sustained symptom resolution

Abbreviations: COVID-19 = coronavirus disease 2019; CVD = cardiovascular disease; ER = emergency room; FiO2 = fractional inspired oxygen; GI = gastrointestinal; PaO2 = ratio of arterial oxygen partial pressure; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SOB = shortness of breath.

aHigh risk population had at least one of the following risk factors: ≥65 years of age, BMI ≥35 for adults or 85% based on CDC growth charts for adolescents, had chronic kidney disease, had type 1 or type 2 diabetes, had immunosuppressive disease, were currently receiving immunosuppressive treatment, had cardiovascular disease (including congenital heart disease) or hypertension, had chronic lung diseases (for example chronic obstructive pulmonary disease, moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, and pulmonary hypertension), had sickle cell disease, had a neurodevelopmental disorder (for example, cerebral palsy) or other conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies), or had a medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation [not related to COVID-19]). High risk factors expanded as the study progressed, therefore not all of these risk factors were included in earlier treatment arms.

bKey inclusion criteria in this table applied to both low-risk and high-risk patients. Patients in the low-risk arms were excluded if they had previously received a SARS-CoV-2 vaccine. Additional inclusion and exclusion criteria for each population can be found at https://clinicaltrials.gov/ct2/show/NCT04634409

cDefined as ≥24 hours of acute care.

Results

Baseline Demographics

BLAZE-4 baseline demographics and disease characteristics for treatment arms 9-14 are described in BLAZE-4 Phase 2 Baseline Demographics.1

BLAZE-4 Phase 2 Baseline Demographics1
	BLAZE-4 Placebo-controlled Portion in Low-risk Subjects	BLAZE-4 Randomized Open-label Portion in High-risk Subjects Treatment Arms 12-13	BLAZE-4 Non-Randomized Open-label Portion in High-risks Subjects Treatment Arm 14
Included treatment arms	BAM 700 mg + ETE 1400 mg + BEB 175 mg BEB 175 mg Placebo	BAM 700 mg + ETE 1400 mg + BEB 175 mg BEB 175 mg	BAM 700 mg + ETE 1400 mg + BEB 175 mg
Total N	N=380	N=150	N=176
Median age, years	35a	50b	51c
Female	56%	52%	56%
White	79%	75%	80%
Hispanic or Latino	36%	18%	28%
Black or African American	19%	18%	16%
Mild COVID-19	74%	75%	73%
Moderate COVID-19	26%	25%	27%
Mean duration of symptoms, days	3.6	4.7	4
Mean viral load by cycle threshold (CT)	24.63	26.66	23.45

Abbreviations: BAM = bamlanivimab; BEB = bebtelovimab; ETE = etesevimab.

a1 placebo patient was aged 65 or older.

b28 patients were aged 65 or older.

c35 patients were aged 65 years or older.

Efficacy

Placebo-Controlled Portion (Low-Risk population; Treatment Arms 9-11)

In this portion of the trial, adult subjects were treated with a single infusion of

bamlanivimab 700 mg, etesevimab 1400 mg, and bebtelovimab 175 mg (N=127)
175 mg bebtelovimab alone (N=125),
or placebo (N=128).1

The majority (96.8%) of the subjects enrolled in these treatment arms did not meet the criteria for high-risk.1

The primary endpoint was the proportion of subjects with persistently high viral load (PHVL) by Day 7.1

PHVL occurred in

26 (21%) patients treated with placebo
16 (13%) patients treated with bamlanivimab 700 mg, etesevimab 1,400 mg, and bebtelovimab 175 mg together (vs placebo: p=0.098; 38% [95% CI: -9%, 65%] relative reduction), and
17 (14%) patients treated with bebtelovimab 175 mg alone (vs placebo: p=0.147; 34% [95% CI: -15%, 62%] relative reduction).1

Secondary endpoints included mean change in viral load from baseline to Day 3, 5, 7, and 11 (see SARS-CoV-2 Viral Load Change from Baseline (Mean ± SE) by Visit from the Placebo-Controlled Portion of BLAZE-4 in Low-Risk Adults).1

SARS-CoV-2 Viral Load Change from Baseline (Mean ± SE) by Visit from the Placebo-Controlled Portion of BLAZE-4 in Low-Risk Adults1

For the secondary endpoint of COVID-19 related hospitalization (defined as ≥24 hours of acute care) or death by any cause by day 29, these events occurred in

2 (1.6%) patients treated with placebo as compared
3 (2.4%) events in patients treated with bamlanivimab 700mg, etesevimab 1400 mg, and bebtelovimab 175 mg together and
2 (1.6%) events in patients treated with bebtelovimab 175 mg alone.1

There was 1 patient treated with bamlanivimab 700 mg, etesevimab 1400 mg, and bebtelovimab 175 mg together who died on day 5. Conclusions are limited as COVID-19 related hospitalization and death rates are expected to be low in a low risk population.1

The median time to sustained symptom resolution as recorded in a trial specific daily symptom diary was

8 days (95% CI: 7, 9 days) for patients treated with placebo
7 days (95% CI: 6, 8 days) for patients treated with bamlanivimab 700 mg, etesevimab 1400 mg, and bebtelovimab 175 mg together (p=.289 vs placebo) and
6 days (95% CI: 5, 7 days) for patients treated with bebtelovimab alone (p=.003 vs placebo).1

Symptoms assessed were cough, shortness of breath, feeling feverish, fatigue, body aches and pains, sore throat, chills, and headache. Sustained symptom resolution was defined as absence of any of these symptoms, except for allowance of mild fatigue and cough, in two consecutive assessments. 1

Randomized Open-Label Portion (High-Risk Population; Treatment Arms 12-13)

In this portion of the trial, subjects were treated with a single infusion of

bamlanivimab 700 mg, etesevimab 1400 mg, and bebtelovimab 175 mg (N=50), or
bebtelovimab 175 mg alone (N=100).1

The majority (91.3%) of the subjects enrolled in these dose arms meet the criteria for high-risk.1

There were 2 pediatric patients enrolled (ages 14 and 17), one in each treatment arm and 20.7% of patients had at least one dose of a COVID-19 vaccine.1

The proportion of patients with COVID-19 related hospitalization (defined as ≥24 hours of acute care) or death by any cause was assessed by Day 29.1

Events occurred in

2 (4%) subjects treated with bamlanivimab, etesevimab, and bebtelovimab together, and
3 (3%) subjects treated with bebtelovimab alone.1

There was 1 subject treated with bebtelovimab 175 mg alone who died on Day 34.1

Mean changes in viral load from baseline to Day 3, 5, 7, and 11 are shown in SARS-CoV-2 Viral Load Change from Baseline (Mean ± SE) by Visit from the Open-label Portion of BLAZE-4.

SARS-CoV-2 Viral Load Change from Baseline (Mean ± SE) by Visit from the Open-label Portion of BLAZE-41

The median time to sustained symptom resolution as recorded in a trial specific daily symptom diary was 7 days for subjects treated with bebtelovimab 175 mg alone.1

Non-Randomized Open-label Portion (High-risk Populations; Treatment Arm 14)

In this portion of the trial, subjects were treated with a single infusion of bamlanivimab 700 mg, etesevimab 1400 mg, and bebtelovimab 175 mg (N=176). The majority (97.7%) of the patients enrolled met the criteria for high-risk, 31% of patients had at least one dose of COVID-19 vaccine, and 2 pediatric patients were enrolled (ages 14 and 15).1

Additional baseline characteristics are presented in BLAZE-4 Phase 2 Baseline Demographics.

The primary objective for this treatment arm was to characterize the safety profile of bamlanivimab 700 mg, etesevimab 1400 mg, and bebtelovimab 175 mg by evaluating adverse events and serious adverse events. Efficacy endpoints included the proportion of subjects with COVID-19 related hospitalization or death by any cause by Day 29, mean change in viral load from baseline to Days 3, 5, 7, and 11, and time to sustained symptom resolution.1

The proportion of subjects with COVID-19 related hospitalization (defined as ≥24 hours of acute care) or death by any cause was assessed by Day 29. Events occurred in 3 subjects, and no subjects died.1

Mean changes in viral load from baseline to

Day 3 was -1.4
Day 5 was -3.1
Day 7 was -4.0, and
Day 11 was -5.4.1

The median time to sustained symptom resolution as recorded in a trial specific daily symptom diary was 8 days.1

Safety

The safety of bebtelovimab is primarily based on exposure of 602 ambulatory (non-hospitalized) subjects who received doses of bebtelovimab, alone or in combination with bamlanivimab and etesevimab, in the phase 1 and phase 2 portions of BLAZE-4, a randomized, single-dose clinical trial.1

The following adverse reactions (i.e., adverse events assessed as causally related) have been observed in those who have received bebtelovimab, alone or in combination with bamlanivimab and etesevimab, at the authorized dose or higher:

infusion-related reactions (n=2, 0.3%)
pruritus (n=2, 0.3%), and
rash (n=5, 0.8%).1

The most common treatment-emergent adverse events observed in subjects treated with bebtelovimab, alone or in combination with bamlanivimab and etesevimab, at the authorized dose or higher, included nausea (0.8%) and vomiting (0.7%).1

There are limited clinical data available for bebtelovimab. Serious and unexpected adverse events may occur that have not been previously reported with bebtelovimab use.1

Overall Benefit-Risk Assessment and Limitations of Data Supporting the Benefits of the Product

Based on the data from BLAZE-4, bebtelovimab has been shown to improve symptoms in patients with mild-to-moderate COVID-19. Additionally, a reduction in SARS-CoV-2 viral load on Day 5 was observed relative to placebo, though the clinical significance of this is unclear.1

The placebo-controlled phase 2 data are limited by enrollment of only subjects without risk factors for progression to severe COVID-19, and the trial was not powered or designed to determine a difference in the clinical outcomes of hospitalization or death between the placebo and bebtelovimab treatment arms. Bebtelovimab has been studied in individuals who have risk factors for progression to severe COVID-19, but the efficacy analyses are limited due to the lack of a concurrent placebo control arm for this population.1

However, based on the totality of scientific evidence available, including the available phase 2 and pharmacokinetic data, along with the nonclinical viral neutralization data for Omicron and other variants of concern, it is reasonable to believe that bebtelovimab may be effective for the treatment of patients with mild-to-moderate COVID-19 to reduce the risk of progression to hospitalization or death.1

In addition, the mechanism of action for bebtelovimab is similar to other neutralizing SARS-CoV-2 monoclonal antibodies, including bamlanivimab and etesevimab, that have data from Phase 3 clinical trials showing a reduction in hospitalization or death in high risk patients infected with other SARS-CoV-2 variants.1

The safety profile of bebtelovimab is acceptable with monitorable risks, and is comparable to other SARS-CoV-2 monoclonal antibodies, including bamlanivimab and etesevimab.1

Considered together, these data support that the known and potential benefits of treatment with bebtelovimab outweigh the known and potential risks 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 and for whom alternative COVID-19 treatment options are not clinically appropriate or accessible.1

Clinical data summarized above were similar for bebtelovimab alone as compared to the combination of bamlanivimab, etesevimab and bebtelovimab administered together. Bebtelovimab retains activity against currently circulating variants.1

Enclosed Fact Sheet

Bebtelovimab Fact Sheet for Health Care Providers

References

1Fact sheet for healthcare providers. Emergency Use Authorization (EUA) of bebtelovimab. US Food and Drug Administration (FDA). 2022.

2United States Food and Drug Administration. Bebtelovimab FDA Emergency Use Authorization letter. Issued February 11, 2022. Accessed February 11, 2022. http://pi.lilly.com/eua/bebtelovimab-eua-fda-authorization-letter.pdf

3Data on file, Eli Lilly and Company and/or one of its subsidiaries.

4A study of immune system proteins in participants with mild to moderate COVID-19 illness (BLAZE-4). ClinicalTrials.gov identifier: NCT04634409. Updated November 15, 2021. Accessed January 7, 2022. https://clinicaltrials.gov/ct2/show/NCT04634409

Date of Last Review: January 12, 2022

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