by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer
November 10, 2020
Lataillade, M et al. Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: Week 96 results of the phase 3 BRIGHTE study. Lancet HIV. November 2020;7(11): e740-51.
Fostemsavir (Rukobia®), is a first-in-class attachment inhibitor that binds directly to the HIV envelope glycoprotein 120. It was approved in July 2020 by the FDA for treatment-experienced patients with multidrug-resistant HIV-1. The 48-week data were previously published (N Engl J Med 2020; 382:1232). This paper is the analyses through week 96. The BRIGHTE study enrolled heavily treatment-experienced PWH failing ART. The average number of prior ART regimens was five. One randomised cohort included patients with one or two fully active ARV drugs who received oral fostemsavir (600 mg bid) or placebo in combination with their ART regimen for 8 days. This was followed by fostemsavir plus optimized background ART. The 2nd cohort included patients with no remaining ART options who received oral fostemsavir plus optimized background ART starting on day 1. Over an 18-month time period, 371 participants were enrolled, including 272 in the randomised arm and 99 in the non-randomised arm. In the randomised cohort, virological suppression increased from 53% at week 24 to 60% at week 96. Viral suppression in the non-randomised cohort was 37% at week 24 and week 96. After 96 weeks the mean increase in CD4 count from baseline was 205/mm3 cells in the randomised cohort and 119 cellsmm3 in the non-randomised cohort. There was drug discontinuation in 7% of all subjects. There were 12 deaths in the randomised cohort and 17 in the non-randomised cohort respectively and those who died had median baseline CD4 count of only 11 cells/mm3.
These data support the efficacy and durability of fostemsavir in PWH with multi-class drug resistance. Response rates were reduced among patients with high baseline viral loads (>100,000 copies/mL) or a very low baseline CD4+ T-cell count (<20 cells per/mm3). The rates of virologic suppression were similar whether the patients had one or two antiretroviral drugs in their initial optimized background therapy. Due to fostemsavir’s novel mechanism of action there is no cross-resistance to currently available classes of ART. The most recent IAS-USA guidelines note “fostemsavir can be used when creating a salvage regimen for individuals with extremely limited treatment options.” The cost of fostemsavir is about $8000.00 for a 1-month supply. There will be more data forthcoming as the BRIGHTE study completion date is December 2024. (NCT02362503)
The author has no conflicts of interest to disclose.
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