Atoltivimab, Maftivimab, and Odesivimab-ebgn (Monograph)

Brand name: Inmazeb
Drug class: Monoclonal Antibodies

Medically reviewed by Drugs.com on Oct 31, 2022. Written by ASHP.

Introduction

Atoltivimab, maftivimab, and odesivimab-ebgn is a monoclonal antibody antiviral agent.

Uses for Atoltivimab, Maftivimab, and Odesivimab-ebgn

Atoltivimab, maftivimab, and odesivimab-ebgn has the following uses:

Atoltivimab, maftivimab, and odesivimab-ebgn is a combination of Zaire ebolavirus glycoprotein-directed human monoclonal antibodies (atoltivimab, maftivimab, and odesivimab), indicated for the treatment of infection caused by Zaire ebolavirus in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection.

Atoltivimab, maftivimab, and odesivimab-ebgn has the following limitation(s) of use:

The efficacy of atoltivimab, maftivimab, and odesivimab-ebgn has not been established for other species of the Ebolavirus and Marburgvirus genera.

Zaire ebolavirus can change over time, and factors such as emergence of resistance, or changes in viral virulence could diminish the clinical benefit of antiviral drugs. Consider available information on drug susceptibility patterns for circulating Zaire ebolavirus strains when deciding whether to use atoltivimab, maftivimab, and odesivimab-ebgn.

Atoltivimab, Maftivimab, and Odesivimab-ebgn Dosage and Administration

General

Atoltivimab, maftivimab, and odesivimab-ebgn is available in the following dosage form(s) and strength(s):

Injection: 241.7 mg of atoltivimab, 241.7 mg of maftivimab, and 241.7 mg of odesivimab per 14.5 mL (16.67 mg/16.67 mg/16.67 mg per mL) in a single-dose vial.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Pediatric Patients

Dosage and Administration

The recommended dosage of atoltivimab, maftivimab, and odesivimab-ebgn is 50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg diluted and administered as a single intravenous infusion.

Atoltivimab, maftivimab, and odesivimab-ebgn must be diluted prior to administration.

Refer to the Full Prescribing Information for information on preparation and administration.

Adults

Dosage and Administration

The recommended dosage of atoltivimab, maftivimab, and odesivimab-ebgn is 50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg diluted and administered as a single intravenous infusion.

Atoltivimab, maftivimab, and odesivimab-ebgn must be diluted prior to administration.

Refer to the Full Prescribing Information for information on preparation and administration.

Cautions for Atoltivimab, Maftivimab, and Odesivimab-ebgn

Contraindications

None.

Warnings/Precautions

Hypersensitivity Reactions Including Infusion-associated Events

Hypersensitivity reactions including infusion-associated events have been reported during and post-infusion with atoltivimab, maftivimab, and odesivimab-ebgn. These may include acute, life-threatening reactions during and after the infusion. Monitor all patients for signs and symptoms including, but not limited to, hypotension, chills and elevation of fever, during and following atoltivimab, maftivimab, and odesivimab-ebgn infusion. In the case of severe or life-threatening hypersensitivity reactions, discontinue the administration of atoltivimab, maftivimab, and odesivimab-ebgn immediately and administer appropriate emergency care.

Infusion could not be completed in 1% of subjects who received atoltivimab, maftivimab, and odesivimab-ebgn due to infusion-associated adverse events. The rate of infusion of atoltivimab, maftivimab, and odesivimab-ebgn may be slowed or interrupted if the patient develops any signs of infusion-associated events or other adverse events.

Specific Populations

Pregnancy

Risk Summary: Zaire ebolavirus infection is life-threatening for both the mother and fetus and treatment should not be withheld due to pregnancy. Available data from the PALM trial and an expanded access program in which pregnant women with Zaire ebolavirusInfection were treated with atoltivimab, maftivimab, and odesivimab-ebgn demonstrate the high rate of maternal and fetal/neonatal morbidity consistent with published literature regarding the risk associated with underlying maternal Zaire ebolavirus infection. These data are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal/fetal outcome. Animal reproduction studies with atoltivimab, maftivimab, and odesivimab-ebgn have not been conducted. Human monoclonal antibodies, such as atoltivimab, maftivimab, and odesivimab-ebgn, are transported across the placenta; therefore, atoltivimab, maftivimab, and odesivimab-ebgn has the potential to be transferred from the mother to the developing fetus.

Clinical Considerations: Maternal, fetal and neonatal outcomes are poor among pregnant women infected with Zaire ebolavirus. The majority of such pregnancies result in maternal death with miscarriage, stillbirth, or neonatal death. Treatment should not be withheld due to pregnancy.

Lactation

Lactation: The Centers for Disease Control and Prevention recommend that patients with confirmed Zaire ebolavirus not breastfeed their infants to reduce the risk of postnatal transmission of Zaire ebolavirus infection.

There are no data on the presence of atoltivimab, maftivimab, and odesivimab-ebgn 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 effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to atoltivimab, maftivimab, or odesivimab-ebgn are unknown.

Pediatric Use

The safety and effectiveness of atoltivimab, maftivimab, and odesivimab-ebgn for the treatment of infection caused by Zaire ebolavirus have been established in pediatric patients from birth to less than 18 years of age. Use of atoltivimab, maftivimab, and odesivimab-ebgn for this indication is supported by evidence from a multi-center, open label, randomized controlled trial of atoltivimab, maftivimab, and odesivimab-ebgn in adults and pediatric subjects that included 39 pediatric subjects birth to less than 18 years of age, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection. The 28-day mortality and safety in adult and pediatric subjects treated with atoltivimab, maftivimab, and odesivimab-ebgn were similar. An additional 38 pediatric subjects from birth to less than 18 years of age received atoltivimab, maftivimab, and odesivimab-ebgn in an expanded access program.

Geriatric Use

Clinical studies of atoltivimab, maftivimab, and odesivimab-ebgn did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Of the 154 subjects with Zaire ebolavirus infection who received atoltivimab, maftivimab, and odesivimab-ebgn in the randomized controlled trial, 5 (3.2%) were 65 years or older. The limited clinical experience has not identified differences in responses between the elderly and younger subjects.

Common Adverse Effects

The most common adverse events (incidence ≥20%) were pyrexia, chills, tachycardia, tachypnea, and vomiting.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Interaction with live vaccine indicated for prevention of Zaire ebolavirus infection: No vaccine interaction studies have been performed. Atoltivimab, maftivimab, and odesivimab-ebgn may reduce the efficacy of the live vaccine. The interval between live vaccination following initiation of atoltivimab, maftivimab, and odesivimab-ebgn therapy should be in accordance with current vaccination guidelines.

Actions and Spectrum

Mechanism of Action

Atoltivimab, maftivimab, and odesivimab-ebgn is an antiviral drug combination of three recombinant human IgG1κ monoclonal antibodies (atoltivimab, maftivimab, and odesivimab) that inhibit Zaire ebolavirus.

Atoltivimab, maftivimab, and odesivimab-ebgn is a combination of three recombinant human IgG1κ monoclonal antibodies each targeting the Zaire ebolavirus glycoprotein (GP). Zaire ebolavirus encodes a sole envelope protein, the glycoprotein, which mediates virus attachment and membrane fusion with the host cell membranes. In addition, GP is expressed on the surface of Zaire ebolavirus-infected host cells making it a target for antibodies that can mediate killing of these cells by antibody dependent cellular cytotoxicity and/or other effector functions. The 3 antibodies that make up the combination can bind the GP simultaneously. The mean K_D values for atoltivimab, odesivimab, and maftivimab were 7.84 nM, 8.26 nM, and 3.34 nM, respectively, as determined by surface plasmon resonance. Maftivimab is a neutralizing antibody that blocks entry of the virus into susceptible cells. Odesivimab is a non-neutralizing antibody that induces antibody-dependent effector function through FcyRIIIa signaling when bound to its target. Odesivimab also binds to the soluble form of Zaire ebolavirus glycoprotein (sGP). Atoltivimab combines both neutralization and FcyRIIIa signaling activities.

Spectrum

In a live virus infection assay on Vero cells, maftivimab neutralized Mayinga, Kikwit, and Makona strains of Zaire ebolavirus, with a concentration between 0.2 and 1.2 nM (0.03 and 0.18 μg/mL) providing 80% inhibition of viral infection in a plaque-reduction neutralization test (PRNT-80). Atoltivimab and odesivimab did not demonstrate any neutralizing activity in this assay. Effector function activity of atoltivimab, maftivimab, and odesivimab-ebgn individual antibodies was assessed with an Ebola virus Makona-GP-expressing cell line and Jurkat/NFAT-Luc/FcγRIIIa reporter effector cells. The EC₅₀ values of atoltivimab and odesivimab were 2.9 nM and 1.6 nM, respectively, whereas maftivimab did not exhibit any FcγRIIIa signaling activity at the maximum concentration tested, 40 nM.

Treatment of Zaire ebolavirus-infected rhesus macaques with a single intravenous dose of atoltivimab, maftivimab, and odesivimab-ebgn (50 mg of atolivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg) generally protected infected animals from Zaire ebolavirus mediated death when drug was administered 5 days post-infection.

Interaction studies with recombinant live Ebola virus vaccines and atoltivimab, maftivimab, and odesivimab-ebgn have not been conducted.

Resistance

No clinical data are available on the development of Ebola virus resistance to atoltivimab, maftivimab, and odesivimab-ebgn. The cell culture development of Ebola virus resistance to atoltivimab, maftivimab, and odesivimab-ebgn has not been assessed to date. A GP_E280G amino acid substitution identified by routine surveillance in the Democratic Republic of the Congo resulted in a loss of neutralization activity of at least 134-fold mediated by the single human monoclonal antibody atoltivimab in a lentivirus-based pseudovirus system. A GP_E564K substitution identified in an infected NHP PK study resulted in a loss of neutralization activity of at least 215-fold mediated by the single human monoclonal antibody maftivimab in a lentivirus-based pseudovirus system. The clinical significance of these substitutions is unknown.

Advice to Patients

Hypersensitivity Reactions Including Infusion-Associated Events

Inform patients that hypersensitivity reactions including infusion-associated events have been reported during and post-infusion with atoltivimab, maftivimab, and odesivimab-ebgn and to immediately report if they experience any symptoms of systemic hypersensitivity reactions.

Lactation

Instruct patients with Zaire ebolavirus infection not to breastfeed because of the risk of passing Zaire ebolavirus to the baby.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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