Ibalizumab

Ibalizumab, sold under the brand name Trogarzo, is a non-immunosuppressive humanised monoclonal antibody that binds CD4, the primary receptor for HIV,^[3] and inhibits HIV from entering cells.^[4] It is a post-attachment inhibitor, blocking HIV from binding to the CCR5 and CXCR4 co-receptors after HIV binds to the CD4 receptor on the surface of a CD4 cell. Post-attachment inhibitors are a subclass of HIV drugs called entry inhibitors.

Ibalizumab

Monoclonal antibody
Type	Whole antibody
Source	Humanized (from mouse)
Target	CD4
Clinical data
Trade names	Trogarzo
Other names	Ibalizumab-uiyk; TMB-355,[1] TNX-355
AHFS/Drugs.com	Monograph
MedlinePlus	a618020
License data	US DailyMed: Ibalizumab
Routes of administration	Intravenous (IV)
ATC code	J05AX23 (WHO)
Legal status
Legal status	US: ℞-only[2] EU: Rx-only
Identifiers
CAS Number	680188-33-4 N
DrugBank	DB12698 Y
ChemSpider	none
UNII	LT369U66CE
KEGG	D09575 Y
ChEMBL	ChEMBL1743029
NIAID ChemDB	209859
NY (what is this?)  (verify)

On March 6, 2018, the U.S. Food and Drug Administration (FDA) approved ibalizumab for multidrug-resistant HIV-1.^[5][6] It is used in combination with other antiretroviral drugs.^[5] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.^[7]

Medical uses

Ibalizumab, in combination with other antiretrovirals, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection.^[2][5]

Development

Ibalizumab is being developed by TaiMed Biologics but was originally developed by Tanox, now part of Genentech. As part of Genentech's takeover of Tanox, the patent for ibalizumab was sold to TaiMed Biologics, a biotech company formed in 2007 with support from the Taiwanese Government through a $20 million investment by the state-owned National Development Fund.^[8][9][10]

Milestones for the intravenous (i.v.) infusion dosage form:^[11]

• 2003: completed a phase-1a clinical trial for i.v. infusion dosage form.
• 2003: granted fast track status by U.S. FDA.
• 2003: completed a phase-1b clinical trial for i.v. infusion dosage form.
• 2006: completed a phase-2a clinical trial for i.v. infusion dosage form.
• 2011: completed a phase-2b clinical trial for i.v. infusion dosage form.
• 2012: completed a phase-1 clinical trial for s.c. injection dosage form.
• 2013: initiated a phase-1/2 clinical trial for s.c. and i.m. injection dosage forms (on-going).
• 2014: granted orphan drug designation for HIV MDR patients by U.S. FDA.^[12]
• 2015: granted breakthrough therapy designation for i.v. infusion dosage form by U.S. FDA.
• 2015: initiated a phase-3 clinical trial for i.v. infusion dosage form (on-going).
• 2016: initiated and intended to complete a rolling BLA submission for i.v. infusion dosage form to U.S. FDA.
• 2016: completion of a phase-3 clinical trial for i.v. infusion dosage form
• 2017: completion of BLA submission and pre-approval inspection for i.v. infusion dosage form to U.S. FDA
• 2018: U.S. market approval (trade name: Trogarzo)

In a Phase III trial with 48 weeks of follow-up, HIV patients with multi-drug resistance tolerated ibalizumab well in combination with other treatments, and 59% of patients achieved viral suppression.^[13]