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 people living with multidrug-resistant HIV-1.2 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, 2403
  • Mean change in CD4+ T-cell counts at Weeks 24, 48, 96, 144, 192, 2403

*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

OPTIMIZED BACKGROUND THERAPIES
In BRIGHTE, RUKOBIA (fostemsavir) was used in combination with other ARVs to optimize the ARV regimen
% of participants who had initial OBTs
containing the following 3:
84%
of participants received
DOLUTEGRAVIR
49%
of participants received
DARUNAVIR
% of participants who had initial OBTs
containing the following as fully active agents​ 4:
64%
of participants received
DOLUTEGRAVIR
17%
of participants received
DARUNAVIR
17%
of participants received
MARAVIROC

The randomized cohort of BRIGHTE included a broad range of people living with MDR HIV⁠-⁠13

Participants in the randomized cohort (n=272) had 1 to 2 classes of ARVs remaining at baseline1,3

Age (range), median years
HIV-1 RNA (range), median log​ 10 copies/mL
CD4​ + T-cell count (range), median cells/mm​ 3

Additional Baseline Information1

42%
2 FULLY ACTIVE
AND AVAILABLE ARVs
IN INITIAL OBT
58%
0-1 FULLY ACTIVE
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 COHORT1,3

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)
Other Races 27 (10)*
HIV-1 RNA (log10 copies/mL)
Median (min, max) 4.7 (1.6-6.9)
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=7), Native Hawaiian/Other Pacific Islander (n=1), Asian (n=2) and other (n=17)3,4. 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.

*All the participants had an HIV-1 RNA level of >400 copies per mL at the time of enrollment.1

‡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.3

Participants in the nonrandomized cohort in BRIGHTE had 0 fully active and approved ARV agents available at screening3

Among participants in the nonrandomized cohort:

BASELINE CHARACTERISTICS IN THE NONRANDOMIZED COHORT (N=99)3,4,5

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)
Other Races 2 (2)*
HIV-1 RNA (log10 copies/mL)
Median (min, max) 4.3 (1.59, 6.61)
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 2402

*Other includes American Indian/Alaskan Native (n=1), Native Hawaiian/Other Pacific Islander (n=0), Asian (n=0), and other (n=1).3,4

†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.5

 

Superior antiviral activity at Day 8

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 82

PRIMARY ENDPOINT (RANDOMIZED COHORT): DECLINE IN MEAN PLASMA VIRAL LOAD

PRIMARY ENDPOINT (RANDOMIZED COHORT): DECLINE IN MEAN PLASMA VIRAL LOAD
PRIMARY ENDPOINT (RANDOMIZED COHORT): DECLINE IN MEAN PLASMA VIRAL LOAD

*Two 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 regimen2

VIROLOGIC RESPONSE WITH RUKOBIA + OBT IN THE RANDOMIZED COHORT: ITT-E POPULATION IN SNAPSHOT ANALYSIS (N=272) AND PARTICIPANTS IN OBSERVED ANALYSIS2

  • 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 Analysis2

Included in the Snapshot Analysis5

  • 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 Analysis5

  • 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).2

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 + OBT2

*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).2  

Proven virologic suppression across subgroups

SECONDARY ENDPOINT (RANDOMIZED COHORT): VIROLOGIC RESPONSE WITH RUKOBIA + OBT Through ~5 YEARS* BY SUBGROUPS4

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)
Other Races 63% (10/16)
Gender
Male 45% (90/198)
Female 43% (30/69)

*Based on BRIGHTE 240-week data.

Virologic failure over time by Snapshot Analysis (ITT-‍E)

PROTOCOL-DEFINED VF WITH RUKOBIA + OBT2

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 subgroups2

SUBGROUP BY BASELINE CD4​ + T-CELL COUNTS (CELLS/mm​ 3)
INCREASE IN CD4​ + T-CELLS FROM BASELINE WITH RUKOBIA + OBT THROUGH ~5 YEARS
mean change from baseline in CD4​ + T-Cell counts (cells/mm​ 3)
SUBGROUP BY BASELINE CD4​ + T-CELL COUNTS (CELLS/mm​ 3)
ALL
(n=272)
<20
(n=72)
<20 to <50
(n=25)
50 to 100
(n=39)
100 to <200
(n=63)
<200
(n=73)
COMBINED DATA
  • 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​2
  • The most immunocompromised participants (<20 cells/mm3 at baseline) experienced the greatest mean CD4+ T-cell increase of 338 cells/mm3 at Week 240​2
*At Week 240, 19 participants did not have their data included in this analysis due to the impact of COVID-19.
SUBGROUP BY BASELINE CD4​ + T-CELL COUNTS (CELLS/mm​ 3)
Combined Data
INCREASE IN CD4​ + T-CELLS FROM BASELINE WITH RUKOBIA + OBT THROUGH ~5 YEARS
mean change from baseline in CD4​ + T-Cell counts (cells/mm​ 3)
  • 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​2
  • The most immunocompromised participants (<20 cells/mm​3 at baseline) experienced the greatest mean CD4​⁠+ T-cell increase of 338 cells/mm​3 at Week 240​2
*At Week 240, 19 participants did not have their data included in this analysis due to the impact of COVID-19.
ALL (n=272)
INCREASE IN CD4​ + T-CELLS FROM BASELINE WITH RUKOBIA + OBT THROUGH ~5 YEARS
mean change from baseline in CD4​ + T-Cell counts (cells/mm​ 3)
  • 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​2
  • The most immunocompromised participants (<20 cells/mm​3 at baseline) experienced the greatest mean CD4​⁠+ T-cell increase of 338 cells/mm​3 at Week 240​2
*At Week 240, 19 participants did not have their data included in this analysis due to the impact of COVID-19.
<20 (n=72)
INCREASE IN CD4​ + T-CELLS FROM BASELINE WITH RUKOBIA + OBT THROUGH ~5 YEARS
mean change from baseline in CD4​ + T-Cell counts (cells/mm​ 3)
  • 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​2
  • The most immunocompromised participants (<20 cells/mm​3 at baseline) experienced the greatest mean CD4​⁠+ T-cell increase of 338 cells/mm​3 at Week 240​2
*At Week 240, 19 participants did not have their data included in this analysis due to the impact of COVID-19.
20 to <50 (n=25)
INCREASE IN CD4​ + T-CELLS FROM BASELINE WITH RUKOBIA + OBT THROUGH ~5 YEARS
mean change from baseline in CD4​ + T-Cell counts (cells/mm​ 3)
  • 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 ​2
  • The most immunocompromised participants (<20 cells/mm​3 at baseline) experienced the greatest mean CD4​⁠+ T-cell increase of 338 cells/mm​3 at Week 240​2
*At Week 240, 19 participants did not have their data included in this analysis due to the impact of COVID-19.
50 to <100 (n=39)
INCREASE IN CD4​ + T-CELLS FROM BASELINE WITH RUKOBIA + OBT THROUGH ~5 YEARS
mean change from baseline in CD4​ + T-Cell counts (cells/mm​ 3)
  • 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​2
  • The most immunocompromised participants (<20 cells/mm​3 at baseline) experienced the greatest mean CD4​⁠+ T-cell increase of 338 cells/mm​3 at Week 240​2
*At Week 240, 19 participants did not have their data included in this analysis due to the impact of COVID-19.
100 to <200 (n=63)
INCREASE IN CD4​ + T-CELLS FROM BASELINE WITH RUKOBIA + OBT THROUGH ~5 YEARS
mean change from baseline in CD4​ + T-Cell counts (cells/mm​ 3)
  • 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​2
  • The most immunocompromised participants (<20 cells/mm​3 at baseline) experienced the greatest mean CD4​⁠+ T-cell increase of 338 cells/mm​3 at Week 240​2
*At Week 240, 19 participants did not have their data included in this analysis due to the impact of COVID-19.
≥200 (n=73)
INCREASE IN CD4​ + T-CELLS FROM BASELINE WITH RUKOBIA + OBT THROUGH ~5 YEARS
mean change from baseline in CD4​ + T-Cell counts (cells/mm​ 3)
  • 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​2
  • The most immunocompromised participants (<20 cells/mm​3 at baseline) experienced the greatest mean CD4​⁠+ T-cell increase of 338 cells/mm​3 at Week 240​2
*At Week 240, 19 participants did not have their data included in this analysis due to the impact of COVID-19.

CD4+ T-cell counts ≥200 cells/mm3 in the majority of participants through ~5 years2

Secondary Endpoint Random Cohort: In CD4​ + T-cells counts of ≥200 CELLS/mm​ 3 through ~5 years
\
Subgroup Analysis
  • 74% (34/46) of the most immunocompromised patients at baseline (CD4​+ T-cell counts of <50 cells/mm​3) met this threshold of ≥200 cells/mm​3 at Week 240​4
Secondary Endpoint NonRANDOMIZED Cohort: In CD4​ + T-cells counts of ≥200 CELLS/mm​ 3 through ~5 years
Subgroup Analysis
  • 74% (34/46) of the most immunocompromised patients at baseline (CD4​+ T-cell counts of <50 cells/mm​3) met this threshold of ≥200 cells/mm3 at Week 240​4

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 YEARS2

*At Week 240,19 participants did not have their data included in this analysis due to the impact of COVID-19.

References:

  1. Kozal M, Aberg J, Pialoux G, et al. Fostemsavir in adults with multidrug-resistant HIV-1 infection. N Egl J Med. 2020;382(13):1232-1243
  2. Aberg J, Shephard B, Wang, et al. Efficacy and safety of fostemsavir plus optimized background therapy in heavily treated-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.
  3. Ackerman P, Thompson M, Molina JM, et al. Long-term efficacy and safety of fostemsavir among subgroups of heavily treatment-experienced adults with HIV-1 AIDS 2021;35(7):1061-1072.
  4. Data on file, ViiV Healthcare
  5. Lataillade M, Lalezari JP, Kozal M, et al. Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study. Lancet HIV. 2020;7(11):740-751.

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