Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection

In patients with limited treatment options, fostemsavir added to their failing regimen (randomised, blinded for 8 days) was associated with a larger reduction in HIV-1 RNA level at day 8 than placebo (difference of -0.63 log10 copies per mL; 95% CI -0.81 to -0.44; p<0.001).

SPS commentary:

Fostemsavir is the prodrug of temsavir, a first-in-class investigational HIV-1 attachment inhibitor, designed to prevent HIV attachment to and entry into CD4+ T cells. The European Medicines Agency are currently reviewing a marketing authorisation application under its accelerated assessment programme.

The initial randomised phase was followed by open-label treatment with fostemsavir plus optimised background therapy. In addition, there was a second cohort of patients with no remaining treatment options, who went straight to open-label treatment (nonrandomised cohort). At week 48, a virological response (HIV-1 RNA level, <40 copies per mL) was seen in 54% and 38%, respectively.

The authors acknowledge the unavoidable limitations of their study, including the inability to include a comparator group beyond the analysis of the primary end point (HIV-1 RNA level at day 8) and the confounder of highly individualised optimised background therapy. The trial is ongoing, and expected to continue until the patients can access fostemsavir through an additional option or rollover study or until marketing approval is in place.


New England Journal of Medicine