containing the following 3:
For heavily treatment-experienced adults with HIV-1 failing therapy. See Full Indication.
BRIGHTE was a Phase 3, international, double-blind, placebo-controlled trial that evaluated the efficacy and safety of RUKOBIA in people living with multidrug-resistant HIV-1.1 The significant antiviral activity of RUKOBIA at Day 8, as well as long-term data through Week 240, is presented below. Additional endpoints in BRIGHTE for RUKOBIA include virologic suppression and change in CD4+ T-cell counts.
BRIGHTE: a large, phase 3 trial with 371 participants1,2
All participants in BRIGHTE were failing on their current ARV regimens with viral loads of ≥400 copies/mL at enrollment
BRIGHTE Trial Design


Secondary Endpoints1:
- Virologic suppression (HIV-1 RNA <40 copies/mL) at Weeks 24, 48, 96, 144, 192, 240
- Mean change in CD4+ T-cell counts at Weeks 24, 48, 96
*Two participants in the RUKOBIA + failing regimen arm who had missing Day 1 HIV-1 RNA values were not included in the analysis at Day 8.
†Within the nonrandomized cohort (n=99), 15 participants received ibalizumab, an investigational agent at the start of the RUKOBIA Phase 3 trial, and 4 received an approved antiretroviral drug and were classified as having a protocol violation.
In BRIGHTE, RUKOBIA (fostemsavir) was used in combination with other ARVs to optimize the ARV regimen

containing the following 3:
The randomized cohort of BRIGHTE included a broad range of people living with MDR HIV-1
Participants in the randomized cohort (n=272) had 1 to 2 classes of ARVs remaining at baseline



Additional Baseline Information2
AND AVAILABLE ARVs
IN INITIAL OBT
AND AVAILABLE ARVs
IN INITIAL OBT
ARV=antiretroviral; HIV-1=human immunodeficiency virus type-1; MDR=multidrug-resistant; OBT=optimized background therapy.
BASELINE CHARACTERISTICS IN THE RANDOMIZED COHORT1,2
Parameter | Total participants (n=272) |
Age, years | |
Median (min, max) | 48 (18-73) |
Age, n (%) | |
<50 years | 162 (60) |
≥50 years | 110 (40) |
Gender, n (%) | |
Male | 200 (74) |
Female | 72 (26) |
Race, n (%) | |
White | 185 (68) |
Black/African American | 60 (22) |
HIV-1 RNA (log10 copies/mL) | |
Median (min, max) | 4.7 (1.6-6.9) |
Other Races | 27 (10)* |
HIV-1 RNA copies/mL, n (%) | |
<400 | 21 (8)† |
400 to <1000 | 10 (4) |
1000 to <100,000 | 161 (59) |
≥100,000 | 80 (29) |
CD4+ T-cells/mm3 | |
Median (min, max) | 99 (0-1160) |
CD4+ T-cells/mm3, n (%) | |
<20 | 72 (26) |
20 to <50 | 25 (9) |
50 to <200 | 102 (38) |
200 to <500 | 58 (21) |
≥500 | 15 (6) |
Number of Fully Active and Available ARVs in Initial OBT, n (%) | |
0 | 16 (6)‡ |
1 | 142 (52) |
2 | 114 (42) |
History of AIDS Diagnosis, n (%) | |
Prior or current history | 231 (85) |
*Other includes American Indian/Alaskan Native (n=8), Native Hawaiian/Other Pacific Islander (n=1), Asian (n=2) and other (n=18). Ethnicity was also recorded for 262 participants (including all US participants and some non-US participants), 107 (29%) of whom identified as Hispanic or Latino.
Can be cited to Ackerman 2021.
*All the participants had an HIV-1 RNA level of >400 copies per ml at the time of enrollment.
‡lncludes 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.
Participants in the nonrandomized cohort in BRIGHTE had 0 fully active and approved ARV agents available at screening
Among participants in the nonrandomized cohort:
BASELINE CHARACTERISTICS IN THE NONRANDOMIZED COHORT (N=99)1,3,5
Parameter | RUKOBIA 600-mg BID + OBT |
Age, years | |
Median (min, max) | 50 (17, 72) |
Age, n (%) | |
<50 years | 44 (44) |
≥50 years | 55 (56) |
Gender, n (%) | |
Male | 89 (90) |
Female | 10 (10) |
Race, n (%) | |
White | 74 (75) |
Black/African American | 23 (23) |
HIV-1 RNA (log10 copies/mL) | |
Median (min, max) | 4.3 (1.59, 6.61) |
Other | 2 (2) |
HIV-1 RNA log10 copies/mL, n (%) | |
<400 | 5 (5) |
400 to <1000 | 4 (4) |
1000 to <100,000 | 75 (76) |
≥100,000 | 15 (15) |
CD4+ T-cells/mm3 | |
Median (min, max) | 41 (0, 641) |
CD4+ T-cells/mm3, n (%) | |
<20 | 40 (40) |
20 to <50 | 14 (14) |
50 to <200 | 25 (25) |
200 to <500 | 18 (18) |
≥500 | 2 (2) |
Number of Fully Active and Available ARVs in Initial OBT, n (%) | |
0 | 80 (81) |
1 | 19 (19)† |
History of AIDS Diagnosis, n (%) | |
Prior or current history | 89 (90) |
- Nonrandomized participants were treated with open-label RUKOBIA 600 mg BID plus OBT from Day 1 through Week 240
*Other includes American Indian/Alaskan Native (n=1), Native Hawaiian/Other Pacific Islander (n=0), Asian (n=0), and other (n=1).1
†Of the 19 participants, 15 received ibalizumab, which was an investigational agent at the start of BRIGHTE. Four patients had 1 fully active ARV class remaining and were classified as a protocol deviations.
Superior antiviral activity at Day 81
BRIGHTE evaluated the efficacy of RUKOBIA among randomized patients (n=272) through Week 240. 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 participants who received RUKOBIA with missing Day 1 HIV-1 RNA values were not included in this analysis.
CI=confidence interval.
Durable virologic suppression demonstrated through ~5 years
In participants who were previously unable to construct a successful regimen1
VIROLOGIC RESPONSE WITH RUKOBIA + OBT IN THE RANDOMIZED COHORT: ITT-E POPULATION IN SNAPSHOT ANALYSIS (N=272) AND PARTICIPANTS IN OBSERVED ANALYSIS1

- At Week 240, 19 participants were unable to have their HIV-1 RNA values assessed due to the impact of COVID-19 and therefore counted as failures in the Snapshot Analysis1
Included in the Snapshot Analysis2
The ITT-E population included all randomized patients who received at least 1 dose of treatment
The FDA Snapshot Algorithm was used to evaluate rates of virologic suppression among all lTT-E patients
In the ITT-E population, missing data or change in OBT was counted as virologic failure
Included in the Observed Analysis2
The Observed Analysis includes only participants for whom HIV-1 RNA values were measured at each study visit
*At Week 240, 5 participants had completed the study by transitioning to locally approved fostemsavir (the first fostemsavir approval was in the US in July 2020).1
FDA=Food and Drug Administration;
ITT-E=intent-to-treat-exposed; OBT=optimized background therapy; PLWH=people living with HIV-1
Rates of virologic suppression in the nonrandomized cohort
SECONDARY ENDPOINT (NONRANDOMIZED COHORT) VIROLOGIC RESPONSE WITH RUKOBIA + OBT1

*At Week 240, 7 participants had completed the study by transitioning to locally approved fostemsavir (the first fostemsavir approval in the US was in July 2020).1
Proven virologic suppression across subgroups
SECONDARY ENDPOINT (RANDOMIZED COHORT): VIROLOGIC RESPONSE WITH RUKOBIA + OBT Through ~5* YEARS BY SUBGROUPS
Subgroup | % of Participants Virologically Suppressed (HIV-1 RNA <40 copies/mL) |
Age, years | |
<35 | 39% (24/61) |
35 to <50 | 48% (48/100) |
>50 | 45% (48/106) |
Race | |
White | 43% (78/183) |
Black or African American | 48% (28/58) |
American Indian or Alaska Native | 43% (3/7) |
Native Hawaiian or other Pacific Islander | 0% (0/1) |
Asian | 50% (1/2) |
Gender | |
Male | 45% (90/198) |
Female | 43% (30/69) |
*Based on BRIGHTE 240-week data.1
Virologic failure over time by Snapshot Analysis (ITT-E)
PROTOCOL-DEFINED VF WITH RUKOBIA + OBT1
PDVF was defined as the following: before Week 24, confirmed HIV-1 RNA ≥400 copies/mL after confirmed suppression to <400 copies/mL or confirmed >1 log10 copies/mL increase in HIV-1 RNA above nadir where nadir is ≥40 copies/mL; at or after Week 24, confirmed HIV-1 RNA ≥400 copies/mL.
• | Through the Week 96 analysis of the randomized cohort (n=272): 11% (n=29) experienced treatment-emergent gp120 resistance-associated substitutions at 4 key sites (S375H/I/M/N/T, M426L/I, M434I/L, M475I/L/V). |
*Through Week 96, the PI for RUKOBIA identifies 69 of 272 (25%) participants in the randomized cohort and 50 of 99 (51%) of participants in the non-randomized cohort as experiencing VF. The definition for VF used in the PI differs from the definition of PDVF. Per the PI, VF=confirmed ≥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).
BID=twice daily; gp120=glycoprotein 120; HIV-1=human immunodeficiency virus type-1; ITT-E=intent-to-treat–exposed; OBT=optimized background therapy; PI=prescribing information; PDVF=protocol-defined virologic failure; VF=virologic failure.
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 240, based on a subgroup summary analysis
- The most immunocompromised participants (<20 cells/mm3 at baseline) experienced the greatest mean CD4+ T-cell increase of 338 cells/mm3 at Week 240
- All participant subgroups categorized by baseline CD4+ T-cell count experienced a mean CD4+ T-cell increase by Week 240, based on a subgroup summary analysis
- The most immunocompromised participants (<20 cells/mm3 at baseline) experienced the greatest mean CD4+ T-cell increase of 338 cells/mm3 at Week 240
- All participant subgroups categorized by baseline CD4+ T-cell count experienced a mean CD4+ T-cell increase by Week 240, based on a subgroup summary analysis
- The most immunocompromised participants (<20 cells/mm3 at baseline) experienced the greatest mean CD4+ T-cell increase of 338 cells/mm3 at Week 240
- All participant subgroups categorized by baseline CD4+ T-cell count experienced a mean CD4+ T-cell increase by Week 240, based on a subgroup summary analysis
- The most immunocompromised participants (<20 cells/mm3 at baseline) experienced the greatest mean CD4+ T-cell increase of 338 cells/mm3 at Week 240
- All participant subgroups categorized by baseline CD4+ T-cell count experienced a mean CD4+ T-cell increase by Week 240, based on a subgroup summary analysis
- The most immunocompromised participants (<20 cells/mm3 at baseline) experienced the greatest mean CD4+ T-cell increase of 338 cells/mm3 at Week 240
- All participant subgroups categorized by baseline CD4+ T-cell count experienced a mean CD4+ T-cell increase by Week 240, based on a subgroup summary analysis
- The most immunocompromised participants (<20 cells/mm3 at baseline) experienced the greatest mean CD4+ T-cell increase of 338 cells/mm3 at Week 240
- All participant subgroups categorized by baseline CD4+ T-cell count experienced a mean CD4+ T-cell increase by Week 240, based on a subgroup summary analysis
- The most immunocompromised participants (<20 cells/mm3 at baseline) experienced the greatest mean CD4+ T-cell increase of 338 cells/mm3 at Week 240
- All participant subgroups categorized by baseline CD4+ T-cell count experienced a mean CD4+ T-cell increase by Week 240, based on a subgroup summary analysis
- The most immunocompromised participants (<20 cells/mm3 at baseline) experienced the greatest mean CD4+ T-cell increase of 338 cells/mm3 at Week 240
CD4+ T-cell counts ≥200 cells/mm3 in the majority of participants through ~5 years
- 74% (34/46) of the most immunocompromised patients at baseline (CD4+ T-cell counts of <50 cells/mm3) met this threshold of ≥200 cells/mm3 at Week 240
- 74% (34/46) of the most immunocompromised patients at baseline (CD4+ T-cell counts of <50 cells/mm3) met this threshold of ≥200 cells/mm3 at Week 240
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 THROUGH ~5 YEARS1

*At Week 240,19 participants did not have their data included in this analysis due to the impact of COVID-19.
References:
- Aberg J, Shepherd B, Wang M, et al. Efficacy and safety of fostemsavir plus optimized background therapy in heavily treatment-experienced adults with HIV-1: Week 240 results of the Phase 3 BRIGHTE study. Poster EPB160. Poster presented at: 24th International AIDS Conference; July 29-August 2, 2022; Montreal, Canada.
- Data on file, ViiV Healthcare.
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