New ARV Approval - Fostemsavir

In July 2020, the U.S. Food and Drug Administration approved fostemsavir (FTR) for treatment of people with multi-drug resistant HIV-1 whose current ARV regimen is failing because of resistance, intolerance, or safety issues. FTR is a novel attachment inhibitor that binds the HIV envelope glycoprotein gp120 and blocks HIV attachment to the CD4 receptor. It is given orally, 600 mg twice daily.

Approval was based on a Phase 3 double blind study (BRIGHTE) in persons with extensive previous treatment and no more than 2 fully active agents available for HIV treatment. The study included 2 cohorts:

  1. a randomized cohort (n=272) whose subjects had 1-2 fully active ARV options and who were treated either with an optimized regimen + FTR or an optimized regimen + placebo. An 8-day lead-in period of adding FTR or placebo to the previous (failing) ART regimen preceded the switch to the optimized regimen.
  2. a nonrandomized cohort (n=99) who had no fully active ARV options. This cohort received open-label FOS plus optimized regimen.

In the randomized cohort, at 24 and 96 weeks, HIV RNA suppression to <200 copies/mL was seen in 68% and 64% of the FTR group, respectively, and HIV RNA <40 copies/mL was seen in 54% and 60%, respectively (Snapshot analysis).

In the nonrandomized group, HIV RNA was <200 copies/mL in 42% at 24 weeks and 39% at 96 weeks, and <40 copies/mL in 37% at both week 24 and week 96.

Virologic failure was associated with the development of new resistance-associated mutations in gp120.

Clinical Bottom Line

Fostemsavir is likely to be very useful in a small but significant group of patients that have few treatment options, because of extensive HIV resistance or tolerability issues. FTR is particularly attractive for advanced lines of therapy because it is an oral medicine, appears to be well tolerated, and has a relatively manageable portfolio of drug-drug interactions.

As with all ARVs it must be combined with other active ARVs to form an effective ART regimen. We will need further experience with FTR to determine optimal components of a FTR-containing salvage regimen, as well as the impact of mutations in gp120, on treatment with FTR or other attachment inhibitors. It also should be noted that, in in vitro studies, HIV subtype AE viruses (common in Southeast Asia) appear to be less susceptible to FTR.

Fostemsavir is marketed as Rukobia.


Fostemsavir prescribing information is available at Drugs@FDA

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