Pentafuside (Trimeris)

Pentafuside (T-20) is a 36 amino acid peptide compound under development by Trimeris for the potential treatment of HIV infection, for which it received US FDA fast track designation in February 1999 [313596,182694]. It corresponds to amino acids 638 to 673 of HIV-1(LA1) transmembrane protein, gp41 [238873]. Pentafuside blocks HIV infection, uniquely, by preventing membrane fusion, an essential process in viral replication. In preclinical studies it blocked infection of cells by HIV and prevented the fusion of one HIV-infected cell with another [171217]. In March 1998, Trimeris signed a letter of intent with DuPont Merck Pharm Co to conduct trials of Merck's efavirenz in combination with pentafuside. The trial planned to enroll up to 48 HIV-infected individuals at three sites in the US, who have begun to fail their existing triple combination therapy. Prior exposure to non-nucleoside reverse transcriptase inhibitors and protease inhibitors, other than indinavir, will be among the exclusion criteria for the study. The first 10 days of the study is a dose-optimization period that will assess the safety, pharmacokinetics and antiviral activity of multiple ascending doses of pentafuside. After completion of this period, subjects will be eligible to participate in an extension period of at least six months, during which pentafuside will be administered in combination with efavirenz and two protease inhibitors [281696]. The use of pentafuside and truncated peptides in combination with other antiviral agents is claimed in WO-09640191.