Clinical Trials and Current Status of Bevirimat

In August 2005, a Phase Ha clinical study of bevirimat was completed successfully. In this randomised double-blind Phase Ha study, bevirimat monotherapy for ten days resulted in statistically significant reductions in viral load compared with placebo, with individual decreases of up to 1.7 log10, at the 100 and 200 mg doses. Genetic analysis of HIV in patients pre- and post-treatment showed no evidence of the development of resistance to the drug. 

In 2008, a Phase lib study of bevirimat in patients failing HIV therapy due to drug resistance was completed successfully. The results of this study demonstrated that patients who have virus with the most commonly occurring amino acids at positions 369, 370, or 371 on Gag are much more likely to respond to bevirimat treatment. In contrast, those patients whose virus has polymorphisms (variants) at these positions are less likely to respond to the drug. Furthermore, pharmacokinetic/pharmacodynamic modelling demonstrated that a trough plasma concentration of greater than 20 pg/mL bevirimat is required for a robust response. 

In the Phase lib study, the mean viral load reduction was —1.18 log10 copies/ mL after 14 days of bevirimat treatment in the patients who were free of key baseline Gag polymorphisms and who had bevirimat trough levels above the 

Most recently, Panacos announced that bevirimat tablet formulation dosed twice daily achieved target plasma levels. After 14 days of bevirimat treatment given twice daily at doses of 200 mg or 300 mg (using the 50 mg tablet), 100% of 32 treatment-naive and treatment-experienced patients in this study had bevirimat plasma concentrations well above the previously identified minimum target of 20 pg/niL. Phase III clinical studies of bevirimat are currently being planned. 

Although the application of HAART has led to a significant improvement in the health and life span of HIV-1-infected patients, several key issues have negatively impacted the efficacy of this treatment approach. A major problem is the increasing prevalence of virus strains that are resistant to approved drugs, which can have a significant adverse impact on treatment effectiveness and disease outcome, highlighting the need for new HIV-1 treatment options. 

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