Ibalizumab, sold under the brand name Trogarzo, is a non-immunosuppressive humanised

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

that binds

CD4 In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic ...

, the primary receptor for

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

, and inhibits HIV from entering cells. It is a post-attachment inhibitor, blocking HIV from binding to the

CCR5 C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines. In humans, the ''CCR5'' gene that encodes the CCR5 pro ...

and

CXCR4 C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the ''CXCR4'' gene. The protein is a CXC chemokine receptor. Function CXCR-4 is an alpha-chemokin ...

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 Entry inhibitors, also known as fusion inhibitors, are a class of antiviral drugs that prevent a virus from entering a cell, for example, by blocking a receptor. Entry inhibitors are used to treat conditions such as HIV and hepatitis D. HIV entry ...

. On March 6, 2018, the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) approved ibalizumab for multidrug-resistant HIV-1. It is used in combination with other antiretroviral drugs. The U.S.

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a pharmaceutical that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medicat ...

Medical uses

Ibalizumab, in combination with other antiretrovirals, is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of human immunodeficiency virus type 1 (HIV-1) infection.

Development

Ibalizumab is being developed by TaiMed Biologics but was originally developed by

Tanox Tanox was a biopharmaceutical company based in Houston, Texas. The company was founded by two biomedical research scientists, Nancy T. Chang and Tse Wen Chang in March 1986 with $250,000, which was a large part of their family savings at that ...

, now part of

Genentech Genentech, Inc., is an American biotechnology corporation headquartered in South San Francisco, California. It became an independent subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within R ...

. 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 The National Development Fund of Iran (NDFI) ( fa, صندوق توسعه ملی) is Iran's sovereign wealth fund. It was founded in 2011 to supplement the Oil Stabilization Fund. NDFI is independent of the government's budget. Based on Article ...

. Milestones for the intravenous (i.v.) infusion dosage form: *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. *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.

References

External links

* {{Portal bar , Medicine Monoclonal antibodies Antiviral drugs Orphan drugs Breakthrough therapy