sábado, 17 de octubre de 2020

FDA Approves INMAZEB (Atoltivimab, Maftivimab, and Odesivimab) for the Treatment of Infection Caused by Zaire ebolavirus in Adult and Pediatric Patients


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FDA Approves INMAZEB (Atoltivimab, Maftivimab, and Odesivimab) for the Treatment of Infection Caused by Zaire ebolavirus in Adult and Pediatric Patients

On October 14, 2020, the U.S. Food and Drug Administration (FDA) approved INMAZEB (atoltivimab, maftivimab, and odesivimab) for the treatment of infection caused by Zaire ebolavirus in adult and pediatric patients, including neonates born to a mother who is reverse transcriptase polymerase chain reaction (RT-PCR) positive for Zaire ebolavirus infection. The approved 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.
Consider available information on drug susceptibility patterns for circulating Zaire ebolavirus strains when deciding whether to use INMAZEB. The efficacy of INMAZEB has not been established for other species of the Ebolavirus and Marburgvirus genera. Additional information regarding dosage and administration as well as warnings and precautions about hypersensitivity reactions including infusion-associated events can be found in the full prescribing information linked below.
Mechanism of Action (MOA) and Pharmacokinetics (PK)
MOA: INMAZEB is an antiviral drug combination of three recombinant human IgG1κ monoclonal antibodies (atoltivimab, maftivimab, and odesivimab) that inhibit Zaire ebolavirus.
General PK: No pharmacokinetic data are available in patients with Zaire ebolavirus infection. The pharmacokinetics of atoltivimab, maftivimab, and odesivimab in healthy subjects 21 to 60 years of age are linear and dose-proportional over the range of 1 mg of atoltivimab, 1 mg of maftivimab, and 1 mg of odesivimab per kg to 50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg (0.02 to 1 times the approved recommended dosage) of INMAZEB following a single intravenous (IV) infusion.
Pharmacokinetic Parameters of INMAZEB Administered IV in Healthy Subjects
50 mg/kga
50 mg/kga
50 mg/kga
Systemic Exposure
Mean (SD) Cmax, mg/L1,220 (101)1,280 (68.0)1,260 (81.2)
Mean (SD) AUCinf, mg day/L17,100 (4,480)18,700 (4,100)25,600 (5,040)
Mean (SD) Volume of Distribution at Steady State, mL/kg58.2 (2.66)57.6 (3.89)56.0 (3.16)
Mean (SD) Elimination Half-Life (days)21.2 (3.36)22.3 (3.09)25.3 (3.86)
Mean (SD) Clearance (mL/day/kg)3.08 (0.719)2.78 (0.558)2.02 (0.374)
a INMAZEB was administered at a total dose of 50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg in a 1:1:1 ratio.
Drug Interactions
Vaccine Interactions: No vaccine interaction studies have been performed. INMAZEB may reduce the efficacy of the live vaccine indicated for prevention of Zaire ebolavirus. Avoid the concurrent administration of a live vaccine during treatment with INMAZEB.The interval between live vaccination following initiation of INMAZEB therapy should be in accordance with current vaccination guidelines.
Use in Specific Populations
The effect of age (< 21 or > 60), renal impairment, or hepatic impairment on the pharmacokinetics of atoltivimab, maftivimab, and odesivimab is unknown.
Lactation: Patients infected with Zaire ebolavirus should be instructed not to breastfeed due to the potential for Zaire ebolavirus transmission.
Efficacy and Safety
Efficacy of INMAZEB was evaluated in a multi-center, open-label, randomized controlled trial in the Democratic Republic of Congo that enrolled 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). Eligible subjects had a positive 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. The primary efficacy endpoint was 28-day mortality. Additional information regarding the efficacy trial can be found in the full prescribing information linked below.
The most common adverse events (incidence ≥ 20%) were pyrexia, chills, tachycardia, tachypnea, and vomiting.

Full prescribing information is available at https://go.usa.gov/x7qFv.

Visit Drugs@FDA at http://go.usa.gov/cMsjT for prescribing and patient information, approval letters, reviews and other information for FDA-approved drug products, which are often available shortly following approval.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at https://www.fda.gov/safety/medwatch/default.htm, by faxing (1-800-FDA-0178), or by mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).
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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.

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