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A subgroup analysis of the week 96 efficacy and safety results evaluating fostemsavir in heavily treatment-experienced HIV-1 infected participants in the phase 3 BRIGHTE study: Results from the randomized cohort
Abstract Content:
Background: FTR is an investigational, first-in-class, attachment inhibitor prodrug of
the active moiety temsavir (TMR). BRIGHTE is an ongoing Phase
3 study evaluating fostemsavir (FTR) in heavily treatment-experienced (HTE)
patients with multidrug resistant HIV-1 and unable to form a viable ARV
regimen. Results through Week 48 were presented previously. Subgroup analyses of Week
96 outcomes for the Randomized Cohort (RC) are presented here.
Methods: HTE participants failing their current ARV regimen (confirmed HIV-1 RNA >400 c/mL) were assigned to the RC if they had 1-2 ARV classes remaining at baseline. Following an 8-day period of blinded fostemsavir or placebo atop failing ARV regimen, participants commenced open-label FTR plus individualized optimized background therapy (OBT). The Non-Randomized Cohort is not described. Virologic and immunologic response was analyzed by demographic and key baseline disease characteristics. Safety results were analyzed by baseline CD4 categories.
Results: Virologic response at Week 96 for the RC was increased from Week 48 and comparable across most subgroups (Table-1) except in subgroups with well-established predictors of reduced response [high baseline viral loads (VL), low baseline CD4 count]. A higher percentage of participants with baseline CD4 counts < 20 cells/µL compared to ≥200 cells/µL had SAEs (46% vs 27%) and deaths (8% vs 3%). Importantly, immunologic improvements were comparable across all subgroups, including a mean increase of 240 cells/µL in participants with baseline CD4 counts < 20 cells/µL.
[Table 1: Virologic and Immunologic Response by Subgroup at Week 96 (Randomized Cohort)]
Conclusions: Subgroup analysis of the Week 96 BRIGHTE data for the RC show remarkable efficacy with FTR across a wide spectrum of HTE patients including comparable and durable rates of virologic response in older, Black and female participants compared to their counterparts. Serious adverse events were predominantly in participants with very low starting CD4 counts. Clinically meaningful improvements in CD4 counts were seen across all subgroups, including those most immune suppressed at baseline.
Methods: HTE participants failing their current ARV regimen (confirmed HIV-1 RNA >400 c/mL) were assigned to the RC if they had 1-2 ARV classes remaining at baseline. Following an 8-day period of blinded fostemsavir or placebo atop failing ARV regimen, participants commenced open-label FTR plus individualized optimized background therapy (OBT). The Non-Randomized Cohort is not described. Virologic and immunologic response was analyzed by demographic and key baseline disease characteristics. Safety results were analyzed by baseline CD4 categories.
Results: Virologic response at Week 96 for the RC was increased from Week 48 and comparable across most subgroups (Table-1) except in subgroups with well-established predictors of reduced response [high baseline viral loads (VL), low baseline CD4 count]. A higher percentage of participants with baseline CD4 counts < 20 cells/µL compared to ≥200 cells/µL had SAEs (46% vs 27%) and deaths (8% vs 3%). Importantly, immunologic improvements were comparable across all subgroups, including a mean increase of 240 cells/µL in participants with baseline CD4 counts < 20 cells/µL.
[Table 1: Virologic and Immunologic Response by Subgroup at Week 96 (Randomized Cohort)]
Conclusions: Subgroup analysis of the Week 96 BRIGHTE data for the RC show remarkable efficacy with FTR across a wide spectrum of HTE patients including comparable and durable rates of virologic response in older, Black and female participants compared to their counterparts. Serious adverse events were predominantly in participants with very low starting CD4 counts. Clinically meaningful improvements in CD4 counts were seen across all subgroups, including those most immune suppressed at baseline.