Ebanga
Ebanga Uses, Dosage, Side Effects, Food Interaction and all others data.
Infection with pathogenic filoviruses, such as Zaire ebolavirus (Ebola virus, EBOV), can cause severe hemorrhagic fever in humans, resulting in frequent outbreaks with case fatality rates as high as 90%. Virtually all steps of the EBOV lifecycle have been targeted for therapeutic development. However, to date, the most successful method appears to be the development of monoclonal antibodies (mAbs) against the GP1,2 surface glycoprotein, as evidenced by the previously approved INMAZEB™ (REGN-EB3, a cocktail of atoltivimab, odesivimab, and maftivimab), the now approved ansuvimab, and ZMapp, which remains in clinical trials. Ebanga, formerly mAb114, is a fully human IgG1 mAb derived from a survivor of the 1995 Kikwit EBOV outbreak 11 years after infection, which displays strong glycan-independent binding to a conserved region of the GP1,2 protein that is responsible for interacting with the host NPC1 protein to mediate EBOV endolysosomal escape, a key step in the EBOV lifecycle. A randomized, controlled trial of four investigational therapies for Ebola virus disease (EVD) in the Democratic Republic of Congo during a previous outbreak that began in 2018 compared ansuvimab, REGN-EB3, ZMapp, and remdesivir, a nucleoside analogue designed to inhibit viral replication, showed ansuvimab and REGN-EB3 to be superior, with improved patient survival and faster viral clearance rates.
Ebanga received FDA approval on December 21, 2020, and is currently marketed as Ebanga by Ridgeback Biotherapeutics, LP. Ebanga is just the second FDA-approved treatment for EVD.
Ebanga is a human IgG1 monoclonal antibody directed against the Zaire ebolavirus GP1,2 surface glycoprotein that is produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cells. The exposure-response relationship of ansuvimab is not currently understood, although the recommended treatment comprises only a single dose. Despite a good overall safety profile, ansuvimab treatment carries a risk of potentially life-threatening hypersensitivity reactions, including infusion-related reactions; in the case of hypersensitivity reactions, ansuvimab should be discontinued, and supportive care initiated immediately.
| Trade Name | Ebanga |
| Generic | Ansuvimab |
| Ansuvimab Other Names | Ansuvimab, ansuvimab-zykl |
| Type | Kit |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Ebanga is a fully human monoclonal IgG1 antibody directed against the GP1,2 surface protein of Zaire ebolavirus that is an effective treatment for Ebola virus disease.
Ebanga is indicated for the treatment of Zaire ebolavirus infection in adult and pediatric patients, including neonates born to a mother who tests positive for Zaire ebolavirus by RT-PCR.
Ebanga has not been shown to be effective against other species within the Ebolavirus and Marburgvirus genera; factors such as the possible emergence of resistant strains suggest local information on circulating Zaire ebolavirus strains should be consulted before initiating treatment.
Ebanga is also used to associated treatment for these conditions: Ebola Virus Infection
How Ebanga works
Zaire ebolavirus (Ebola virus, EBOV) is one of six species within the Ebolavirus genus, which itself is one of six genera within the Filoviridae family. Infection with pathogenic filoviruses such as EBOV in humans can result in hemorrhagic fever with very high fatality rates (25-90%). Following infection, a variable latency period of ~2-21 days occurs before the onset of symptoms, which are vague at first, including fatigue, fever, aches, myalgia, and gastrointestinal complaints, but that progress in severe disease to both internal and external bleeding, multiorgan failure, secondary infections, meningoencephalitis, hypotension, and shock. The pathogenesis of EBOV is poorly understood but is thought to be multifactorial: immune suppression, cytokine dysregulation, vascular dysfunction, and abnormal coagulation.
EBOV is a non-segmented negative-sense RNA virus whose genome comprises seven genes, including the GP1,2 glycoprotein involved in host cell entry and subsequent viral escape into the cytoplasm. GP1,2 binds to one of several possible host receptors such as various lectins and TYRO3 receptor tyrosine kinases, β1 integrins, the asialoglycoprotein receptor, human folate receptor-α, and TIM1. Following internalization into endolysosomes by macropinocytosis, GP1,2 is cleaved by host cathepsins into a fusion-competent form termed GPCL, which subsequently binds the Niemann-Pick C1 protein (NPC1) to induce fusion of the host endolysosomal and viral membranes that releases the viral nucleocapsids into the host cytoplasm.
The EBOV GP is a class I fusion protein comprising GP1 and GP2 subunits, transcribed as a single gene and proteolytically processed into individual subunits linked by disulphide bonds; three subunit heterodimers subsequently associate to form the mature chalice-shaped GP1,2. Ebanga (formerly mAb114) is a fully human IgG1 monoclonal antibody (mAb) derived from an Ebola virus disease (EVD) survivor from the 1995 Kikwit EBOV outbreak 11 years after infection that binds to GP1,2 over a region encompassing both the glycan cap and GP1 core, although the glycan cap is dispensable for binding. Furthermore, structural studies reveal that ansuvimab binds to regions of the GP1 core thought to be important for GPCL interaction with NPC1 and blocks NPC1-GP interactions in vitro. Further in vitro studies revealed that ansuvimab exhibits strong GP binding (EC50 of 0.02 μg/mL), the ability to neutralize GP-expressing lentiviral particles (IC50 of 0.09 μg/mL), and strong antibody-dependent cell-mediated cytotoxicity (ADCC) at concentrations of 0.03 μg/mL. Hence, the proposed ansuvimab mechanism of action is through direct blockage of EBOV endolysosome escape and ADCC-mediated killing of EBOV-infected cells.
Toxicity
Toxicity information regarding ansuvimab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as hypotension, tachycardia, tachypnea, pyrexia, chills, diarrhea, vomiting, and hypersensitivity reactions including infusion-related reactions. Symptomatic and supportive measures are recommended.
Food Interaction
No interactions found.Volume of Distribution
The steady-state volume of distribution in healthy volunteers administered a single dose of 5 mg/kg, 25 mg/kg, or 50 mg/kg ansuvimab was 5.08 ± 0.88, 3.93 ± 0.50, and 4.16 ± 0.74 L, respectively.
Elimination Route
The absorption of ansuvimab was evaluated in 18 healthy volunteers aged 18-60 years in an open-label phase 1 study. Ebanga administered at 5 mg/kg produced a Cmax of 198.45 ± 45.15 μg/mL, a Tmax of 3.21 ± 1.56 h, and an AUC0-28d of 1480 ± 304 μg*day/mL. The corresponding values for 25 mg/kg were: Cmax of 829.38 ± 237.40 μg/mL, Tmax of 2.99 ± 2.16 h, and AUC0-28d of 8586 ± 900 μg*day/mL, while the corresponding values for 50 mg/kg were: Cmax of 1961.21 ± 339.83 μg/mL, Tmax of 2.75 ± 1.63 h, and AUC0-28d of 18588 ± 3627 μg*day/mL. Overall, the pharmacokinetic profile of ansuvimab is consistent with other IgG1 monoclonal antibodies.
Half Life
The half-life of ansuvimab following a single administration of 5 mg/kg, 25 mg/kg, or 50 mg/kg was 20.1 ± 6.9, 26.7 ± 3.8, and 23.6 (no calculated standard deviation available) days, respectively.
Clearance
The clearance of ansuvimab following a single administration of 5 mg/kg, 25 mg/kg, or 50 mg/kg was 199 ± 45, 108 ± 21, and 115 ± 15 mL/day, respectively.
Innovators Monograph
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