Currently Enrolling Trials
Inmazeb is a combination of Zaire ebolavirus glycoprotein-directed human monoclonal antibodies (atoltivimab, maftivimab, and odesivimab).
Inmazeb is specifically 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.
Inmazeb is supplied as an infusion for intravenous administration. The recommended dosage of Inmazeb is 50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg diluted and administered as a single intravenous infusion.
Mechanism of Action
Inmazeb 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. 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.
Adverse effects associated with the use of Inmazeb may include, but are not limited to, the following:
Clinical Trial Results
The FDA approval of Inzameb was based on PALM, a multi-center, open-label, randomized controlled trial sponsored by the National Institute of Allergy and Infectious Diseases. The trial was conducted in the Democratic Republic of Congo, where an outbreak began in August 2018, and enrolled 681 subjects of all ages, including pregnant women, with documented Zaire ebolavirus infection and symptoms of any duration who were receiving optimized standard of care (oSOC). Subjects were randomized to receive Inmazeb (50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg) intravenously as a single infusion, an investigational control 50 mg/kg intravenously every third day, for a total of 3 doses, or other investigational drugs. Eligible subjects had a positive reverse transcriptasepolymerase chain reaction (RT-PCR) for the nucleoprotein (NP) gene of Zaire ebolavirus and had not received other investigational treatments (with the exception of experimental vaccines) within the previous 30 days. Neonates ≤7 days of age were eligible if the mother had documented infection. Neonates born to a mother who had cleared Zaire ebolavirus following a course of her assigned investigational medication were also eligible to be enrolled at investigator discretion regarding the likelihood that the neonate was infected. The primary efficacy endpoint was 28-day mortality. The PALM trial was stopped early on the basis of a pre-specified interim analysis showing a statistically significant reduction in mortality for Inmazeb (34% mortality) compared to control (51% mortality).