ViiV Healthcare announced it has submitted an NDA to the U.S. FDA seeking approval of fostemsavir for use in combination with other antiretroviral agents in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection who are unable to form a suppressive regimen due to resistance, intolerance or safety considerations.
This NDA submission is supported by data from the pivotal phase III BRIGHTE study in heavily treatment-experienced people living with multidrug-resistant HIV. The partially-randomized, international, double-blind, placebo-controlled trial was conducted in 371 heavily treatment-experienced adults living with HIV-1 infection with multidrug resistance. were enrolled in either a randomized or non-randomized cohort defined as follows:
- Randomized cohort (n = 272), patients had 1, but no more than 2, fully active and available antiretroviral agent(s) at screening which could be combined as part of an efficacious background regimen. Patients received either blinded fostemsavir 600 mg twice daily (n = 203) or placebo (n = 69) in addition to their current failing regimen for 8 days of functional monotherapy. Beyond Day 8, patients received open-label fostemsavir 600 mg twice daily plus an investigator-selected optimized background therapy (OBT).
- Non-randomized cohort (n = 99), patients had no fully active and approved antiretroviral agent(s) available at screening. Patients were treated with open-label fostemsavir 600 mg twice daily plus OBT from Day 1 onward. The use of an investigational drug(s) as a component of the OBT was permitted.
The primary endpoint analysis, based on the adjusted mean decline in HIV-1 RNA from Day 1 at Day 8 in the randomized cohort, demonstrated superiority of fostemsavir to placebo (0.79 vs. 0.17 log10 copies/mL decline, respectively; P<0.0001, Intent-to-Treat-Exposed [ITT-E] population). In the randomized cohort, HIV-1 RNA <40 copies/mL was achieved in 53%, 54%, and 60% of subjects at Weeks 24, 48, and 96, respectively (ITT-E). Mean changes in CD4+ cell count from baseline continued to increase over time (i.e., 90 cells/mm3 at Week 24, 139 cells/mm3 at Week 48, and 205 cells/mm3 at Week 96). The most common adverse reactions were nausea and diarrhea.
Fostemsavir has been granted FDA Fast Track and Breakthrough Therapy Designations.
Fostemsavir is an investigational prodrug of temsavir, is a first-in-class HIV-1 attachment inhibitor that works by binding directly to the glycoprotein 120 (gp120) subunit on the surface of the virus. By binding to this location on the virus, fostemsavir blocks HIV from attaching to host immune system CD4+ T-cells and other immune cells, thereby preventing HIV from infecting those cells and multiplying. Because of this unique mechanism of action, there is no demonstrated resistance to other classes of antiretrovirals, which may help patients who have become resistant to most other medicines.