Ibalizumab is a humanized monoclonal antibody to CD4, the cell surface receptor for the HIV-1 envelope glycoprotein (gp120), which is used to treat patients with multidrug resistant HIV-1 infection. Ibalizumab therapy has not been associated with serum enzyme elevations or to instances of clinically apparent drug induced liver injury.
Ibalizumab (eye' ba liz' ue mab) is a recombinant humanized monoclonal antibody to CD4, the cell surface receptor for the HIV-1 envelope glycoprotein 120 (gp120). Ibalizumab does not block the binding of gp120 to CD4 but rather inhibits the conformation changes in the CD4/gp120 complex that allows binding to a second cellular receptor, chemokine-receptor-4 (CXCR4), thus inhibiting HIV replication. Clinical trials of ibalizumab in heavily treatment-experienced HIV-positive patients with multidrug resistance have shown that it decreased HIV RNA levels and resulted in full suppression in over half of patients. Ibalizumab was approved for use in the United States in 2018 for therapy (in combination with other antiretroviral agents) of patients with multidrug resistant HIV-1 infection. Ibalizumab is available in solution in single dose vials of 200 mg/1.33 mL under the brand name Trogarzo. Ibalizumab is administered as an intravenous infusion. The recommended dose is an initial loading dose of 2,000 mg followed by a maintenance dose of 800 mg every 2 weeks. Side effects are generally mild and include injection site reactions, diarrhea, dizziness, nausea and rash. Rare but potentially severe adverse events include hypersensitivity reactions and immune reconstitution syndrome.
The prelicensure clinical trials of ibalizumab included a limited number of patients, many of whom had other serious comorbidities including cirrhosis and chronic hepatitis B and C. In these trials, serum aminotransferase elevations occurred in 14% to 25% of patients, but the abnormalities were generally mild and self-limited and often attributable to other underlying conditions. Serum bilirubin levels were elevated above 2.5 mg/dL in 5% of patients, but no patient developed both serum aminotransferase and bilirubin elevations or clinically apparent liver injury. There were no serious hepatic adverse events or deaths that were attributed to ibalizumab therapy. Since approval, there have been no published reports of clinically apparent acute liver injury attributed to ibalizumab, but it has had limited general use.
Mechanism of Liver Injury
Ibalizumab is a human monoclonal antibody and is unlikely to be inherently hepatotoxic. Recombinant proteins are often metabolized in the cells on which they act but are also metabolized in the liver, largely to small peptides and amino acids which may be reused to synthesize proteins and are unlikely to be toxic or immunogenic. Ibalizumab therapy does not appear to affect other CD4 receptor functions.
Drug Class: Antiviral Agents; Monoclonal Antibodies
Ibalizumab – Trogarzo®
|DRUG||CAS REGISTRY NUMBER||MOLECULAR FORMULA||STRUCTURE|
|Ibalizumab||680188-33-4||Monoclonal Antibody||Not Available|
Top of page