Background: BRIGHTE is an ongoing Phase 3 study evaluating fostemsavir (FTR) in heavily treatment-experienced (HTE) patients with multidrug resistant HIV-1 who are unable to form a viable antiretroviral (ARV) regimen. FTR is a prodrug metabolized to temsavir (TMR), a first-in-class, investigational attachment inhibitor, which binds directly to HIV-1 gp120 preventing initial attachment to CD4 receptors on T-cells, and other host immune cells, thereby blocking infection.
Methods: Participants were assigned to the Randomized (RC) or Non-randomized Cohort (Non-RC) (Figure-1). Results through Week 48 were presented previously. Week 96 results are presented here.

Figure 1 - Study Design
[Figure 1 - Study Design]

Results: Participants had a median baseline CD4 count of 80 cells/µL (100 RC;41 Non-RC); 86% had AIDS. At Week 96, 60% of RC achieved virologic suppression (an increase of 6% from Week 48 despite continued attrition, Table-1); mean increase in CD4 was 205 cells/µL. Of RC with baseline CD4< 200, 67% increased to CD4≥200; 56% from < 50 to ≥200 cells/µL.

 Randomized Cohort N=272Non-Randomized Cohort N=99
 Snapshot n (%)Observed n (%)Snapshot n (%)Observed n (%)
Week 24144 (53)141/246 (57)37 (37)37/89 (42)
Week 48146 (54)145/233 (62)38 (38)40/83 (48)
Week 96163 (60)170/214 (79)37 (37)39/66 (59)
[Table 1 - Summary of Virologic Response (HIV-1 RNA <40 c/mL) Over Time by Snapshot Analysis (Intent-to-Treat Exposed Population) and Observed Analysis]

Through Week 96, there were higher rates of severe AEs in the Non-RC vs. RC: SAE (48%/34%), Grade 3-4 AEs (49%/29%), and deaths (16%/4%). Overall, 38% had an SAE; 3% were drug related. 7% discontinued due to AE. Most deaths were attributed to complications of advanced AIDS and acute infection.
Conclusions: Fostemsavir-containing regimens remained generally well-tolerated through Week 96 with no new safety signal and few AE-related discontinuations. Virologic and immunologic response continued to improve in this difficult-to-treat population. BRIGHTE results support continued development of FTR as a potentially important treatment option for HTE patients with multi-drug resistant HIV.