Long-term (96-week) safety of fostemsavir (FTR) in heavily treatment-experienced (HTE) adults infected with multidrug-resistant (MDR) HIV-1 (BRIGHTE Phase 3 study)

BACKGROUND: BRIGHTE is an ongoing study evaluating the gp120 attachment inhibitor FTR in HTE adults with MDR HIV-1.
METHODS: Participants assigned to the Randomized Cohort (1-<2 antiretroviral classes remaining) or Non-randomized Cohort (no fully active approved antiretrovirals remaining) received FTR 600mg BID plus optimized background therapy. Frequency of adverse events (AEs), time to onset and duration were analysed.
RESULTS: Most participants (94%, 347/370) experienced '¥1 AE [Table 1] over 96 weeks of FTR exposure [110.4 median weeks (0.1-171.4)]; most AEs were infection-related. Common drug-related AEs were nausea (9%), diarrhoea (5%) and headache (3%). Overall, musculoskeletal and renal AEs occurred in 15% and 14% of participants, respectively. Eight (2%) cases of IRIS occurred. AEs leading to discontinuation were primarily due to complications of advanced AIDS.
38% of participants experienced '¥1 serious AE (SAE) with pneumonia most common. Few SAEs were drug-related (3%). Infection-related SAEs generally occurred in those most immunosuppressed (baseline CD4+ count <20 cells/mm³). Death occurred for 8% of participants; common causes were acute infections and AIDS-related events. The most severe AEs, including Grade 3-4 AEs, SAEs and deaths, occurred disproportionately in the Non-randomized Cohort and those most immunosuppressed at baseline [Table 1]. Participants with Grade 3-4 liver and renal toxicities [Table 2] had confounding risk factors.




CONCLUSIONS: Cumulative safety findings through the 96-week interim analysis of BRIGHTE are consistent with what is expected in an HTE population with high rates of advanced HIV and comorbid disease. The safety and tolerability profile of FTR is favourable in the intended-use population.