The Food and Drug Administration (FDA) has approved Rukobia (fostemsavir; ViiV Healthcare), in combination with other antiretrovirals, for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.

Rukobia represents a new class of antiretroviral therapy. Fostemsavir is a prodrug that is hydrolyzed to its active form, temsavir, an HIV-1 attachment inhibitor, following oral administration. By binding directly to the gp120 subunit within the HIV-1 envelope glycoprotein gp160, temsavir selectively inhibits the interaction between the virus and cellular CD4 receptors, thereby preventing attachment.

The approval was based on data  from the phase 3 BRIGHTE trial that included 371 heavily treatment-experienced patients with multiclass HIV-1 resistance. Most patients were enrolled in a randomized cohort (n=272) in which they received either blinded fostemsavir 600mg twice daily (n=203) or placebo (n=69) in addition to their current failing regimen for 8 days of functional therapy. After day 8, patients received open-label fostemsavir plus an investigator-selected optimized background therapy. The study also included a nonrandomized cohort (n=99) in which patients received open-label fostemsavir plus optimized background therapy from day 1. 

The primary efficacy end point was the adjusted mean decline in HIV-1 RNA from day 1 to day 8 with fostemsavir vs placebo in the randomized cohort. Results showed that treatment with fostemsavir was found to be superior to placebo, with a significantly greater decrease in levels of HIV-1 RNA (-0.791 [95% CI, -0.885, -0.698] vs -0.166 [95% CI, -0.326, -0.007] log10 copies/mL, respectively; treatment difference: -0.625 log10 copies/mL (95% CI, -0.810, -0.441; P <.0001). 

At Week 24, 53% of patients treated with fostemsavir plus optimized background therapy achieved HIV RNA suppression (HIV-1 RNA <40 copies/mL); by Week 96, 60% achieved HIV-1 RNA <40 copies/mL. Additionally, mean changes in CD4+ cell count from baseline increased over time (90 cells/mm3 and 205 cells/mm3 at weeks 24 and 96, respectively).

With regard to safety, the most common adverse reaction reported was nausea. Serious adverse events may also include immune reconstitution syndrome and elevations in hepatic transaminases in patients with hepatitis B or C virus co-infection. At higher than recommended dosages, fostemsavir has also been shown to significantly prolong the QTc interval.

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Rukobia is supplied as 600mg extended-release tablets.

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