Clinical Pharmacology Corner: FDA Approves TROGARZO (ibalizumab-uiyk)

FDA Approves TROGARZO (ibalizumab-uiyk) for Treatment of Human Immunodeficiency Virus Type 1 (HIV-1) Infection in Heavily Treatment-Experienced Adults with Multidrug Resistant HIV-1 Infection Failing Current Antiretroviral Regimen

On March 6, 2018, the U.S. Food and Drug Administration (FDA) approved TROGARZO (ibalizumab-uiyk), a human immunodeficiency virus type 1 (HIV-1) antiretroviral drug, for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen. The approved recommended dosage of TROGARZO is a single intravenous (IV) loading dose of 2,000 mg followed by a maintenance IV dose of 800 mg every 2 weeks. TROGARZO is administered after dilution in 250 mL of 0.9% sodium chloride injection, USP.

Immune reconstitution inflammatory syndrome has been reported with TROGARZO in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment.

Mechanism of Action (MOA), General Pharmacokinetics (PK), and Pharmacodynamics (PD)

• MOA: Ibalizumab-uiyk, a recombinant humanized monoclonal antibody, is a CD4 domain 2-directed post-attachment HIV-1 inhibitor.
• Dose Proportionality : Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, AUC increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg, and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg (0.01 to 0.9 times the approved recommended loading dose based on a 70 kg patient). 
• Time to Steady-State: Steady-state concentrations were achieved after the first maintenance dose.
• Distribution: The volume of distribution of ibalizumab-uiyk was 4.8 L.
• Immunogenicity: All subjects enrolled in clinical trials were tested for presence of anti-ibalizumab antibodies. One sample tested positive with low titer anti-ibalizumab antibodies. No adverse reaction or reduced efficacy was attributed to the positive sample reported in this subject. 

Efficacy and Safety

Efficacy of TROGARZO was demonstrated in a single arm, multicenter clinical trial of heavily treatment-experienced HIV-infected subjects with multidrug resistant HIV-1. Additional information regarding the efficacy trial can be found in the full prescribing information linked below.

The most common adverse reactions (incidence ≥ 5%) were diarrhea, dizziness, nausea, and rash.

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

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 athttp://www.fda.gov/medwatch/report.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.