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IBALIZUMAB FDA Product Insert
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CROI: IBALIZUMAB SUSCEPTIBILITY IN PATIENT HIV ISOLATES RESISTANT TO ANTIRETROVIRALS - (03/07/18)
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TROGARZO, a CD4-directed post-attachment HIV-1 inhibitor, in combination with other antiretroviral(s), is indicated for the
treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with
multidrug resistant HIV-1 infection failing their current antiretroviral regimen. (1)
-------------- DOSAGE AND ADMINISTRATION -----------
TROGARZO is administered intravenously (IV) as a single
loading dose of 2,000 mg followed by a maintenance dose of
800 mg every 2 weeks after dilution in 250 mL of 0.9% Sodium
Chloride Injection, USP. (2.1)
------------- DOSAGE FORMS AND STRENGTHS ----------
Injection: 200 mg/1.33 mL (150 mg/mL) in a single-dose vial. (3)
Cross-Resistance
Phenotypic and genotypic test results revealed no evidence of cross-resistance between ibalizumab-uiyk and any of the approved classes of anti-retroviral drugs (CCR5 co-receptor antagonists, gp41 fusion inhibitors, integrase strand transfer inhibitors [INSTIs], non-nucleos(t)ide reverse transcriptase inhibitors [NNRTIs], nucleos(t)ide reverse transcriptase inhibitors [NRTIs], or protease inhibitors [PIs]). Ibalizumab-uiyk is active against HIV-1 resistant to all approved antiretroviral agents and exhibits antiretroviral activity against R5-tropic, X4-tropic, and
dual-tropic HIV-1.
Decreased susceptibility to ibalizumab-uiyk following multiple dose administrations of ibalizumab-uiyk has been observed in some subjects. Cell culture studies performed with HIV-1 variants with reduced susceptibility to
ibalizumab-uiyk indicate that phenotypic changes associated with resistance to ibalizumab-uiyk do not alter susceptibility to other approved agents and do not result in the selection of CD4-independent viral isolates.
Antiviral Activity in Antiretroviral-Resistant Virus
Subjects enrolled in TMB-301 were heavily treatment-experienced subjects infected with multidrug resistant HIV-1. Ibalizumab-uiyk inhibited 38 baseline isolates at a median EC50 value of 31 ng/mL (range of 13 to 212 ng/mL; mean 39 ± 35 ng/mL) with a median MPI of 97% (range of 41-100%; mean 91 ± 14%). For 10 subjects in
TMB-301 who failed treatment, at the time of failure the median ibalizumab-uiyk EC50 value was 566 ng/mL (range of 148 to >54,900 ng/mL; mean 11,768 ± 21,650 ng/mL) representing an EC50 value shift of >18-fold. For the HIV-1 derived from the same subjects, the median MPI was 55% (range of 43-72%; mean 56 ± 8%)
representing a 42 percentage point reduction.
Decreased Susceptibility
Decreased susceptibility to ibalizumab-uiyk, as defined by a decrease in MPI, has been observed in some subjects experiencing virologic failure and may be associated with genotypic changes in the HIV-1 envelope coding sequence that results in the loss of potential N-linked glycosylation sites (PNGS) in the V5 loop of gp120. The clinical significance of decreased susceptibility to ibalizumab-uiyk has not been established.
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