Fusion and Attachment Inhibitors

• Attachment and Fusion Inhibitors
• Drugs No Longer in Development

Note: Several fact sheets describe drugs that are being tested against HIV:

• Fact Sheet 410: nucleoside analog reverse transcriptase inhibitors (nukes)
• Fact Sheet 430: non-nucleoside analog reverse transcriptase inhibitors (NNRTIs or non-nukes)
• Fact Sheet 440: protease inhibitors
• Fact Sheet 470: other antiretroviral drugs in development
• Fact Sheet 480: immune therapies

These drugs have not been approved by the Food and Drug Administration (FDA) for use against HIV.

Attachment and Fusion Inhibitors

This is a new class of anti-HIV drugs. They are intended to protect cells from infection by HIV by preventing the virus from attaching to a new cell and breaking through the cell membrane. Researchers hope that these drugs can prevent infection of a cell by either free virus (in the blood) or by contact with an infected cell.

Because digestive acids break them down, most of these drugs are given by injections or intravenous infusion.

AK602 is a CCR5 blocker being developed by Kumamoto University in Japan. It is in early human trials.

AMD070 by AnorMed blocks the CXCR4 receptor on CD4 T-cells to inhibit HIV fusion. Development is on hold because of liver problems in animal studies.

BMS-378806 is an attachment inhibitor that attaches to gp120, a part of the virus, not the target cell. It is in Phase I trials.

GSK 706769 by GlaxoSmithKline is a new CCR5 antagonist in Phase I trials.

HGS004 by Human Genome Sciences, a monoclonal antibody CCR5 blocker, successfully completed a Phase II trial.

Ibalizumab (TNX-355) by TaiMed Biologics blocks the CD4 receptor. It is a genetically engineered drug, a "monoclonal antibody." It is being studied as an intravenous infusion every two or four weeks. It is administered along with antiretroviral medications. No significant side effects have shown up yet. It is in Phase II trials.

INCB 9471 by Incyte Corporation has successfully completed Phase II trials in healthy volunteers. It has shown very good tolerability. However, Incyte will not conduct further studies. It will license the drug to another company and will stop working in HIV.

PF-232798 by Pfizer is a CCR5 blocker. It is in Phase II trials.

PRO 140 by Progenics is now in Phase II trials. It blocks fusion by binding to a receptor protein on the surface of CD4 cells. PRO140 has been granted fast-track status by the FDA. It is being studied as an intravenous infusion and by subcutaneous injections.

SCH532706 by Schering is in Phase I studies. It is best used as part of a regimen that includes ritonavir where it can be administered once daily.

SP01A by Samaritan Pharmaceuticals is an HIV entry inhibitor in a Phase II trial.

TAK-652 by Takeda blocks binding to the CCR5 receptor. It is in a Phase II study.

TBR-652 by Tobira Therapeutics is a CCR5 blocker. It is in Phase II trials.

VCH-286 by ViroChem Pharma is a CCR5 antagonist. A Phase II trial has received regulatory approval.

Vicriviroc (SCH417690, formerly called Schering D) by Schering Plough blocks the CCR5 receptor on CD4 cells. No serious toxicities have been seen. It is in Phase III trials.

Drugs No Longer in Development

The following drugs are no longer being developed for use against HIV:

• AMD3100 (fusion inhibitor) by AnorMed
• Aplaviroc (GW873140) by GlaxoSmithKline. Development was suspended due to liver toxicity.
• BMS488043 and BMS806 (attachment inhibitors by Bristol-Myers Squibb, replaced by BMS378806
• FP21399 (CCR5 blocker) by Fuji Pharmaceuticals
• PRO542 is no longer being developed. Instead, Progenics is focusing on PRO140.
• T-1249 (fusion inhibitor) by Roche and Trimeris -- development was halted in early 2004.