Title

Phase 3 study of fostemsavir in heavily treatment-experienced HIV-1-infected participants: BRIGHTE week 24 subgroup analysis in randomized cohort subjects

Presenter

Peter Ackerman

Authors

G. Pialoux¹, M. Kozal², J. Aberg³, P. Cahn⁴, M. Thompson⁵, J.-M. Molina⁶, B. Grinsztejn⁷, R. Diaz⁸, A. Lazzarin⁹, G. Latiff¹⁰, M. Gummel¹¹, A. Pierce¹², C. Llamoso¹³, M. Lataillade¹³, P. Ackerman¹³

Institutions

¹Hopital Tenon, Paris, France, ²Yale University School of Medicine, New Haven, United States, ³Icahn School of Medicine at Mount Sinai, New York, United States, ⁴Fundación Huesped, Buenos Aires, Argentina, ⁵AIDS Research Consortium of Atlanta, Atlanta, United States, ⁶Hôpital Saint Louis, Paris, France, ⁷Instituto de Pesquisa Clínica Evandro Chagas FIOCRUZ, Rio de Janeiro, Brazil, ⁸Federal University of São Paulo, São Paulo, Brazil, ⁹Ospedale San Raffaele, Milan, Italy, ¹⁰Maxwell Centre, Durban, South Africa, ¹¹GlaxoSmithKline, Biostatistics, Upper Providence, United States, ¹²ViiV Healthcare, Clinical Development, Research Triangle Park, United States, ¹³ViiV Healthcare, Clinical Development, Branford, United States

Background: The BRIGHTE study evaluates fostemsavir (FTR), a first-in-class attachment inhibitor, in HIV-1 infected heavily treatment-experienced (HTE) patients with limited treatment options (≤2 antiretroviral [ARV] classes remaining) and who are failing their current ARV therapy. Fostemsavir demonstrated superior efficacy relative to placebo (0.79 log₁₀ c/mL for FTR vs 0.17 log₁₀ c/mL for placebo; p< 0.0001) after 8 days of functional monotherapy. Fifty-four percent of subjects in the Randomized Cohort (1-2 remaining ARV classes at baseline), receiving FTR plus optimized background therapy (OBT), achieved virologic suppression (HIV-1 RNA < 40 c/mL) at Week 24 (W24). The mean CD4+ T-cell count increased by 90 cells/µL from baseline at W24.
Methods: Here we present a subgroup analysis of immunologic response (observed mean change in CD4+ count at W24) and of virologic efficacy (adjusted mean change in log₁₀ HIV-1 RNA at Day 8 and percent with HIV-1 RNA < 40 c/mL at W24 by snapshot algorithm) in participants within the Randomized Cohort.
Results: Increase in mean CD4+ counts at W24 was similar regardless of subgroup, including baseline CD4+ category. Participants with baseline CD4+ counts < 20 cells/µL averaged an increase of 97 cells/µL at W24, which is comparable in magnitude to mean change in all other baseline CD4+ categories. Reduction in baseline viral (VL) at Day 8 of FTR monotherapy was also similar across all subgroups. A lower virologic response rate at WK24 was observed in participants with a baseline VL ≥100,000 c/mL (38%) vs. VL < 100,000 c/mL (60%) and in participants with a baseline CD4+ < 50 cells/µL (37%) vs. CD4+ ≥50 cells/µL (63%).
Conclusions: In fostemsavir-treated HTE participants with 1 or 2 remaining ARV classes, improvement in CD4+ count through W24 was clinically significant and similar for all subgroups; including participants with very low incoming CD4+ counts at baseline (< 20 cells/µL). Virologic response at W24 was similar across subgroups except high baseline VL (≥100,000 c/mL) and low baseline CD4+ count (< 50 cells/µL); two well-recognized determinants of virologic response.

[Efficacy and Immunologic Responses by Subgroup at Day 8 and at Week 24 (Randomized Cohort)]