Bevirimat (PA-457 or MPC-4326)

Bevirimat is the first experimental HIV maturation inhibitor. Development of bevirimat has been halted by its developer, Myriad Genetics.

Maturation inhibitors reduce HIV viral load by interfering with the production of the HIV capsid protein. If this protein is not assembled, any HIV particles that are produced are defective and unable to infect other human cells. Bevirimat is a betulinic acid derivative that interferes with the production of the HIV capsid by preventing cleavage of the precursor Gag protein.

The drug has had a troubled history with formulation and bioavailability issues. Myriad Genetics bought bevirimat, then called MPC-4326, from Panacos in 2009. Later in the year, results from Study 204, a phase II dose-ranging clinical trial were presented. The drug showed poor efficacy in individuals who have developed Gag polymorphisms (a group not restricted to treatment-experienced individuals). A genotypic test has been developed to predict those without Gag polymorphisms who are most likely to respond to the drug.1,2 

A larger phase IIb study of bevirimat, formulated as a 100mg tablet, was underway when Myriad announced (in June 2010) that it was halting its development programme. The company did not reveal the cause of the decision, but said in a press statement that it will seek to partner with another company to develop its maturation inhibitors further.

References

  1. Bloch M et al. Efficacy, safety and pharmacokinetics of MPC-4326 (bevirimat dimeglumine) 200mg BID and 300mg BID monotherapy administered for 14 days in subjects with HIV-1 infection. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, abstract H-1230, 2009
  2. Lalezari J et al. Pharmacokinetics and safety of a novel 100 mg tablet formulation of MPC-4326 in subjects with HIV-1 infection. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, abstract A1-1309, 2009
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