MOAB0102
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Title
Week 96 safety and efficacy of the novel HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced participants infected with multi-drug resistant HIV-1 (BRIGHTE study)
Presenter
Max Lataillade
Authors
M. Lataillade1, J. Lalezari2, J. Aberg3, J.-M. Molina4, M. Kozal5, P. Cahn6, M. Thompson7, R. Diaz8, A. Castagna9, M. Gummel10, M. Gartland11, A. Pierce11, P. Ackerman1, C. Llamoso1
Institutions
1ViiV Healthcare, Branford, United States, 2Quest Research, San Francisco, United States, 3Icahn School of Medicine at Mount Sinai, New York, United States, 4Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France, 5Yale University School of Medicine, New Haven, United States, 6Fundacion Huesped, Buenos Aires, Argentina, 7AIDS Research Consortium of Atlanta, Atlanta, United States, 8The Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil, 9Clinic of Infectious Diseases, Vita-Salute San Raffaele University, Milan, Italy, 10GlaxoSmithKline, Upper Providence, United States, 11ViiV Healthcare, Research Triangle Park, United States

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.