For heavily treatment-experienced adults with HIV-1 failing therapy. See Full Indication.
Clinical Trial
BRIGHTE was a Phase 3, international, double-blind, placebo-controlled trial that evaluated the efficacy and safety of RUKOBIA in participants with HIV-1 who were heavily treatment-experienced (HTE) with limited treatment options remaining.1 The significant antiviral activity of RUKOBIA at Day 8, as well as long-term data through Week 96, is presented below. Additional endpoints in BRIGHTE for RUKOBIA include virologic suppression and change in CD4+ T-cell counts.
BRIGHTE: a large, 96-week, Phase 3 trial with 371 participants
All participants in BRIGHTE:
- Were failing on their current ARV regimens with viral loads of ≥400 copies/mL1
- Had ≤2 classes of ARVs remaining at baseline due to resistance, intolerability, contraindication, or other safety concerns
ARV classes were determined to be unavailable due to1:
- Drug resistance
- Contraindications
- Tolerability issues
- Other safety concerns
ARV=antiretroviral.
BRIGHTE Trial Design
Primary Endpoint (Randomized Cohort)1:
- Adjusted mean plasma HIV-1 RNA log10 change from Day 1 at Day 8
Secondary Endpoints1:
- Virologic suppression at Weeks 24, 48, and 96
- Change in CD4+ T-cell counts at Weeks 24, 48, and 96
*Investigator-selected OBT.
†There was considerable variability in the number of ARVs included in initial OBT, fully active and otherwise. The majority of participants received dolutegravir (84%) as a component of OBT and approximately half of participants (49%) received darunavir. The most common fully active agents used in initial OBT were dolutegravir (64%), darunavir (17%), and maraviroc (17%).1
ARV=antiretroviral; BID=twice daily; OBT=optimized background therapy.
BRIGHTE included a broad range of heavily treatment-experienced (HTE) people living with HIV-1 (PLWH)
Among participants in the randomized cohort1,2:
Baseline Characteristics in the Randomized Cohort (n=272)1,2
ǂIncludes participants who never initiated OBT, were incorrectly assigned to the randomized cohort, or had 1 or more active antiretroviral agents available at screening but did not use these as part of the initial OBT.1
Nonrandomized participants in BRIGHTE had 0 fully active and approved ARV agents available at screening
Baseline Characteristics in the NONRandomized Cohort (n=99)1,2
§Of the 19 participants, 15 received ibalizumab, which was an investigational agent at the start of BRIGHTE. Four participants had 1 fully active ARV class remaining and were classified as protocol deviations.
Significant antiviral activity at Day 81
BRIGHTE evaluated the efficacy of RUKOBIA among randomized patients (n=272) through Week 96. The primary endpoint was based on the adjusted mean plasma HIV-1 RNA log10 change from Day 1 at Day 81
PRIMARY ENDPOINT (RANDOMIZED COHORT): Decline in mean plasma viral
load
ǁTwo patients who received RUKOBIA with missing Day 1 HIV-1 RNA values were not included in this analysis.
CI=confidence interval.
Durable virologic suppression demonstrated over 96 weeks
In PLWH who were previously unable to construct a successful regimen1
SECONDARY ENDPOINT (RANDOMIZED COHORT):
VIROLOGIC RESPONSE WITH RUKOBIA + OBT3
- The ITT-E population included all randomized participants who received at least 1 dose of treatment1
- The FDA Snapshot Algorithm was used, in which patients who had missing HIV-1 RNA values or who changed the composition of their optimized background therapy were classified as having had virologic failure
¶Snapshot analysis did not include baseline.
FDA=Food and Drug Administration;
ITT-E=intent-to-treat-exposed; OBT =optimized background therapy; PLWH=people living with HIV-1
POST-HOC ANALYSIS (RANDOMIZED COHORT, OBSERVED ANALYSIS)
VIROLOGIC RESPONSE WITH RUKOBIA + OBT1,3
- The observed analysis includes only participants for whom HIV-1 RNA values were measured at each study visit2
Rates of virologic suppression in the nonrandomized cohort
SECONDARY ENDPOINT (NONRANDOMIZED COHORT)
VIROLOGIC RESPONSE WITH RUKOBIA + OBT3
¶Snapshot analysis did not include baseline.
POST-HOC ANALYSIS (NONRANDOMIZED COHORT)
VIROLOGIC RESPONSE WITH RUKOBIA + OBT3
Virologic suppression across subgroups
Comparable rates of virologic suppression were achieved across demographic subgroups in the randomized cohort at Week 96, including older and minority HTE patients1,3
SECONDARY ENDPOINT (RANDOMIZED COHORT): VIROLOGIC RESPONSE
WITH RUKOBIA + OBT AT WEEK 96 BY SUBGROUPS
Robust CD4+ T-cell recovery across subgroups
All participant subgroups categorized by baseline CD4+ T-cell count experienced a mean CD4+ T-cell increase by Week 96, based on a subgroup summary analysis1
SECONDARY ENDPOINT (RANDOMIZED COHORT): INCREASE IN CD4+ T-CELLS FROM BASELINE
WITH RUKOBIA + OBT BY WEEK 963
- Changes in mean CD4+ T-cell counts from baseline also increased over time for participants with HIV-1 RNA ≥40 copies/mL at Week 96 (n=51). The mean increase was 172 cells/mm3 at Week 961
Robust CD4+ T-cell recovery despite no fully active and approved ARV agents in OBT
SECONDARY ENDPOINT (NONRANDOMIZED COHORT): INCREASE IN CD4+ T-CELLS FROM BASELINE
WITH RUKOBIA + OBT AT WEEK 963
CD4+ T-cell counts ≥200 cells/mm3 in the majority of randomized participants at Week 961
SECONDARY ENDPOINT (RANDOMIZED COHORT): CD4+ T-CELL COUNTS OF ≥200 CELLS/mm3 WITH RUKOBIA + OBT1
fmol=femtomole.; W=week.
- 56% (40/71) of immunocompromised participants at baseline (CD4+ T-cell counts of <50 cells/mm3) met this threshold of ≥200 cells/mm3 at Week 961
Virologic failure and treatment-emergent substitutions for RUKOBIA
Through the Week 96 analysis of the randomized cohort (n=272):
- 25% (n=69) experienced virologic failure#
- 11% (n=29) experienced treatment-emergent gp120 resistance-associated substitutions at 4 key sites (S375H/I/M/NT, M426L/I, M4341/L, M4751/L/V)
#Virologic failure was defined as confirmed HIV-1 RNA ≥400 copies/mL after prior confirmed suppression to <400 copies/mL, ≥400 copies/mL at last available prior to discontinuation, or >1 log10 copies/mL increase in HIV-1 RNA at any time above nadir level (≥40 copies/mL).
gp120=glycoprotein 120.
References:
- Data on file, ViiV Healthcare.
- Kozal M, Aberg J, Pialous G, et al. Fostemsavir in adults with multi-drug-resistant HIV-1 infection. N Engl J Med. 2020;382(13):1232-1243.
- Lataillade M, Lalezari J, Aberg J, et al. 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). Poster presented at: 10th International AIDS Society Conference on HIV Science; July 21-24, 2019; Mexico City, Mexico.
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