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 patients 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, pivotal Phase 3 trial of 371 HTE patients with HIV-11

All patients 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 patients received dolutegravir (84%) as a component of OBT and approximately half of patients (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 patients with advanced HIV-1 disease1

Patients in the randomized cohort had 1-2 fully active and approved ARV agents available at screening1

Baseline Characteristics in the Randomized Cohort (n=272)1

ǂIncludes patients 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 patients in BRIGHTE had 0 fully active and approved ARV agents available at screening1

Nonrandomized patients were treated with open-label RUKOBIA 600 mg twice daily plus OBT from Day 1 through Week 96

Baseline Characteristics in the NONRandomized Cohort (n=99)1

§Of the 19 patients, 15 received ibalizumab, which was an investigational agent at the start of BRIGHTE. Four patients had 1 fully active, approved ARV class remaining and were classified as a protocol violation.

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.

Sustained rates of virologic suppression in patients who were previously unable to construct a viable regimen1

Despite having failing regimens at study entry, 60% of randomized patients who received RUKOBIA + OBT achieved virologic suppression at Week 961

SECONDARY ENDPOINT (RANDOMIZED COHORT):
VIROLOGIC RESPONSE WITH RUKOBIA + OBT3

  • The ITT-E population included all randomized patients 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.

POST-HOC ANALYSIS (RANDOMIZED COHORT, OBSERVED ANALYSIS)
VIROLOGIC RESPONSE WITH RUKOBIA + OBT1,3

  • The observed analysis includes only patients 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 key 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, even in the most immunocompromised patients1

All patient 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 patients with HIV-1 RNA ≥40 copies/mL at Week 96 (n=51). The mean increase was 172 cells/mm3 at Week 961

CD4+ T-cell recovery in the nonrandomized cohort

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 patients at Week 961

SUB-ANALYSIS (RANDOMIZED COHORT): CD4+ T-CELL COUNTS OF ≥200 CELLS/mm3 WITH RUKOBIA + OBT1

  • 56% (40/71) of immunocompromised patients 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% experienced virologic failure#
  • 10% experienced treatment-emergent gp120 resistance-associated substitutions at 4 key sites (S375N, M426L/I, M434I/L, M475I/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:

  1. Data on file, ViiV Healthcare.
  2. Kozal M, Aberg J, Pialous G, et al. Fostemsavir in adult with multi-drug-resistant HIV-1 infection. N Engl J Med. 2020;382(13):1232-1243.
  3. 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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