Enfurvitide (Fuzeon) was the first antiretroviral drug from the new class of HIV fusion & entry inhibitors approved in 2003 by the FDA. Unlike all currently approved anti-HIV drugs (reverse transcriptase and protease inhibitors), Fuzeon blocks the virus from entering the human immune cell, thereby, preventing HIV replication, but suffers from an inconvenient subcutaneous administration regimen. The need for new classes of antiretroviral drugs has become apparent because of increasing concern about the long-term toxic effects of existing drugs, the need to combat HIV-1 variants that are resistant to treatment, and the frequency of treatment change in drug-experienced patients. New treatment options target the viral entry into the cell including HIV fusion inhibitors and HIV coreceptor antagonists. The entry of HIV in the target cells is a multistep process involving interaction of viral envelope glycoproteins gp120 and gp41 with cell surface receptors. Binding to CD4 is followed by engagement of specific chemokine receptors (CCR5 and CXCR4), triggering molecular rearrangements in the envelope transmembrane subunit that result in membrane fusion. The CCR5 co-receptor has become a prime target in the new class of HIV fusion & entry inhibitors as is evidenced by Pfizer’s oral maraviroc currently undergoing regulatory review in the US and the EU and a full pipeline of clinical stage and preclinical CCR5 antagonists.

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