Fostemsavir in Heavily Treatment-Experienced Individuals Living with HIV-1: Insights from the Phase 3 BRIGHTE Study

Fostemsavir (RukobiaTM, ViiV Healthcare, Research Triangle Park, NC), a prodrug of the first-in-class attachment inhibitor temsavir, was developed to provide a much-needed new therapeutic option for heavily treatment-experienced (HTE) people living with HIV-1 (PLWH) who are unable to form a suppressive regimen from remaining viable antiretroviral (ARV) agents because of multidrug resistance, contraindications, prior intolerance, or other safety considerations [1-4]. Effective treatment for this vulnerable population can be complicated by other challenges in addition to multidrug resistance, including low CD4+ T-cell counts, comorbidities, psychosocial factors, and non-adherence to complex regimens [4-9]. Regulatory approval of fostemsavir was based on results from the phase 3 BRIGHTE study (ClinicalTrials.gov, NCT02362503) showing that, in HTE adults who were failing their current ARV regimen with limited remaining treatment options, fostemsavir combined with optimized background therapy (OBT) was generally well tolerated and resulted in a distinctive trend of increasing virologic response rates (by intention-to-treat–exposed [ITT-E] Snapshot and observed analysis) and increases in CD4+ T-cell counts through 96 weeks [1,4]. In this commentary, we dig deeper into the rationale for the BRIGHTE study design, expand upon the remarkable patterns of virologic and immunologic response observed in BRIGHTE, and consider how these patterns may be related to the unique mode of action of fostemsavir (temsavir). The BRIGHTE Clinical Study Design was Appropriate for HTE PLWH