Clinical trial design and data for RUKOBIA (fostemsavir)

BRIGHTE: Largest Phase 3 trial with the longest reported follow-up (336 weeks, approaching 7 years) in the MDR HIV-1 population1,2

BRIGHTE is an ongoing Phase 3, international, double-blind, placebo-controlled trial evaluating the efficacy and safety of RUKOBIA in people living with multidrug-resistant HIV-1. The significant antiviral activity of RUKOBIA at Day 8, as well as long-term data through Week 336, is presented below. 

Additional endpoints in BRIGHTE for RUKOBIA include virologic suppression and change in CD4+ T-cell counts, also presented below.

All participants in BRIGHTE were living with MDR HIV-1 and failing their current ARV regimens with a viral load of ≥400 copies/mL at enrollment.

At Week 336, 80 participants were still enrolled in BRIGHTE (randomized cohort, n=72; nonrandomized, n=8).1

BRIGHTE trial design1-4

BRIGHTE trial design infographic.

Primary endpoint3

  • Adjusted mean plasma HIV-1 RNA log10 change from Days 1 to 8 (randomized cohort)

*Fully active based on susceptibility (current or historical resistance) and availability (participant is tolerant of, eligible for, and willing to take [in the case of enfuvirtide only] the antiretroviral). Use of investigational agents in OBT was permitted in the nonrandomized cohort.1

†Participants in the randomized cohort were randomly assigned 3:1 to receive fostemsavir 600 mg twice daily or placebo + current failing regimen for 8 days, after which all participants received open-label RUKOBIA.1

‡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.

§Investigator-selected OBT (based on resistance testing and treatment history).3

In BRIGHTE, RUKOBIA was used in combination with other ARVs to optimize the ARV regimen5,6

  • DTG, DRV, and TFV were some of the most common ARVs included in the optimized background therapy

Common ARVs in the initial OBT in the BRIGHTE cohorts6

Bar graphs showing common antiretroviral drugs among BRIGHTE trial participants.

3TC or FTC was included in 50% and 77% of OBT in the randomized cohort and nonrandomized cohort, respectively. ARVs in the figure above include those that were in the initial OBT for at least 10% of study participants.5

In the randomized cohort, most participants (94%) were taking 1 or 2 ARVs in initial OBT: participants taking 0 (6%, n=15), 1 (52%, n=142), or 2 (42%, n=115) fully active ARVs.1

In the nonrandomized cohort, participants were taking either 0 (80%, n=79) or 1 (20%, n=20) fully active ARVs in initial optimized background therapy.1
 

*For the nonrandomized cohort, experimental ARVs other than RUKOBIA were assumed to be fully active.6

†Based on the screening criteria for activity (according to screening and historical resistance measures).6

‡4 participants had 1 fully active and available ARV at screening, and 16 received ibalizumab, which was still investigational at study start.6

§Includes participants who discontinued the study during the blinded period and never started OBT, not treated with a fully active ARV in initial OBT despite having a fully active ARV available at screening, and inadvertently assigned to the randomized cohort despite having no fully active ARV available at screening.6

BRIGHTE included a broad range of adults living with MDR HIV-11,3,7

1 to 2 active ARV classes

Baseline characteristics for randomized cohort (n=272)

BRIGHTE trial baseline characteristics for randomized cohort.

Baseline CD4+ counts for randomized cohort (n=272)

Pie chart showing baseline CD4 counts for randomized cohort.

Additional baseline characteristics for randomized cohort

Additional baseline characteristics for randomized cohort.

*Patients in the Hispanic ethnic group could also be included in a racial group.2

No fully active ARV agents

Baseline characteristics for nonrandomized cohort (n=99)

BRIGHTE trial baseline characteristics for nonrandomized cohort.

Baseline CD4+ counts for nonrandomized cohort (n=99)

Pie chart showing baseline CD4 counts for nonrandomized cohort.

Additional baseline characteristics for nonrandomized cohort

Additional baseline characteristics for nonrandomized cohort.

*One patient was 17 years of age at enrollment and was classified as a protocol deviation.

†Patients in the Hispanic ethnic group could also be included in a racial group.2

‡Of the 20 participants, 16 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 protocol deviations.3

Superior antiviral activity at Day 8

Primary endpoint (randomized cohort): Decline in mean plasma viral load

BRIGHTE trial primary endpoint: Mean change in plasma viral load.

*Two participants who received RUKOBIA with missing Day 1 HIV-1 RNA values were not included in this analysis.

Rates of virologic suppression1,2,6,8

Virologic response (HIV-1 RNA <40 copies/mL) for RUKOBIA + OBT in the randomized cohort (additional endpoint)1,2,6,8

Results are descriptive.

Line graph showing virologic response for RUKOBIA plus OBT for randomized cohort.
  • In the Observed Analysis at Week 336, 80 participants were still enrolled in BRIGHTE (randomized cohort, n=72; nonrandomized cohort, n=8). Due to attrition, analyses after Week 240 used only observed data (participants with HIV-1 RNA measured at each visit), potentially favoring treatment successes1
  • In the Observed Analysis, the proportion of patients with a virological response of HIV-1 RNA <200 copies/mL at Week 240 was 92%8
  • In the Snapshot Analysis, the proportion of patients with a virological response of HIV-1 RNA <200 copies/mL at Week 240 was 50%8‡
  • The study was impacted by COVID-19–related disruptions in care access and follow-up around the Week 192 time point1

Included in the Snapshot Analysis6

  • The ITT–E population included all randomized participants 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 Analysis6

  • The Observed Analysis included only participants for whom HIV-1 RNA values were measured at each study visit, potentially favoring treatment successes

*At Week 240, 12 participants had completed the study by transitioning to locally approved fostemsavir (the first fostemsavir approval was in the US in July 2020).2

†Baseline values are not reported.

‡In the randomized cohort at Week 96, the proportion of patients with HIV-1 RNA <200 copies/mL was 64% (ITT–E, Snapshot Analysis).8

Virological response (HIV-1 RNA <40 copies/mL) for RUKOBIA + OBT in the nonrandomized cohort (exploratory endpoint)*

Results are descriptive.

Line graph showing virologic response for RUKOBIA plus OBT for nonrandomized cohort.
  • In the Observed Analysis at Week 336, 80 participants were still enrolled in BRIGHTE (randomized cohort, n=72; nonrandomized cohort, n=8). Due to attrition, analyses after Week 240 used only observed data (participants with HIV-1 RNA measured at each visit), potentially favoring treatment successes
    – At Week 240, 5 participants were unable to have their HIV-1 RNA values assessed due to the impact of COVID-19
  • In the Snapshot Analysis, the proportion of patients with a virological response of HIV-1 RNA <200 copies/mL at Week 240 was 23%§
  • In the Observed Analysis, the proportion virologic response of HIV-1 RNA <200 copies at Week 240 was 77%

Included in the Snapshot Analysis6

  • The ITT–E population included all randomized participants 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 Analysis6

  • The Observed Analysis included only participants for whom HIV-1 RNA values were measured at each study visit, potentially favoring treatment successes

*For the nonrandomized exploratory treatment arm (N=99), 16 participants (n=20) received ibalizumab, which was still investigational at study start.1

†At Week 240, 12 participants had completed the study by transitioning to locally approved fostemsavir (the first fostemsavir approval was in the US in July 2020).2

‡Baseline values are not reported.

§In the nonrandomized cohort at Week 96, the proportion of patients with HIV-1 RNA <200 copies/mL was 39% (ITT–E, Snapshot Analysis).8

Virologic suppression across subgroups8

Virologic response with RUKOBIA + OBT at ~5 years by subgroups (Snapshot Analysis ITT–E)8*

Results are descriptive.

Subgroup % of Participants Virologically
Suppressed (HIV-1 RNA <40
copies/mL) at Week 240
Age, years
<35 39% (24/61)
35 to <50 48% (48/100)
≥50 45% (48/106)
Gender
Male 45% (90/198)
Female 43% (30/69)
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)

Virologic outcomes (HIV-1 RNA <40 copies/mL) by subgroup (randomized cohort, ITT–E population, Snapshot algorithm) at Week 96:

  • Male, 59% (118/200); female, 63% (45/72)
  • White, 56% (103/185); Black or African American/Other Races, 69% (60/87)
  • Age <50, 59% (96/162); age ≥50, 61% (67/110)

*ITT–E population, Snapshot Analysis. The ITT–E population included all randomized participants who received at least 1 dose of treatment. The FDA Snapshot algorithm was
used to evaluate rates of virologic suppression among all ITT–E participants. In the ITT–E population, missing data or change to OBT was counted as virologic failure.6

No fully active ARV agents*

Virologic response with RUKOBIA + OBT at ~5 years by subgroups (exploratory Snapshot Analysis ITT–E)8†

Results are descriptive.

Subgroup % of Participants Virologically
Suppressed (HIV-1 RNA <40
copies/mL) at Week 240
Age, years
<35 8% (1/12)
35 to <50 39% (11/28)
≥50 15% (8/52)
Gender
Male 23% (19/83)
Female 11% (1/9)
Race
White 26% (18/70)
Black or African
American		 10% (2/20)
American Indian
or Alaska Native		 0% (0/1)
Native Hawaiian or
Other Pacific Islander		 N/A
Asian N/A
Other Races 0% (0/1)

*For the nonrandomized exploratory treatment arm (n=99), 15 participants received ibalizumab, an investigational agent, at the start of BRIGHTE, and 4 patients were incorrectly assigned to the nonrandomized cohort.1

†ITT–E population-Snapshot analysis. The ITT–E population Included all participants who received at least one dose of study treatment. The FDA Snapshot algorithm was
used to evaluate rates of virologic suppression among all ITT–E participants. In the ITT–E population, missing data or change to OBT was counted as virologic failure.6

Protocol-defined virologic failure (Snapshot Analysis, ITT-E) at ~5 years2

Protocol-defined VF with RUKOBIA + OBT

Randomized Cohort RUKOBIA
600 mg BID
Week 96 (N=272), n (%) Week 240 (N=267), n (%)
63 (23)* 80 (29)

PDVF was defined as the following: before Week 24, confirmed (or last available before discontinuation) 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 (or last available before discontinuation) HIV-1 RNA ≥400 copies/mL.1

  • Through Week 96 in the randomized cohort, 55% (29/53) of participants with virologic failure who had post-baseline data had treatment-emergent gp120 resistance-associated substitutions at 4 key sites (S375H/I/M/N/T, M426L/I, M434I/L, M475I/L/V)

Protocol-defined VF with RUKOBIA + OBT

Nonrandomized Cohort RUKOBIA
600 mg BID
Week 96 (N=99), n (%) Week 240 (N=92), n (%)
49 (49)* 53 (54)

PDVF was defined as the following: before Week 24, confirmed (or last available before discontinuation) 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 (or last available before discontinuation) HIV-1 RNA ≥400 copies/mL.1

  • Through Week 96 in the randomized cohort, 55% (29/53) of participants with virologic failure who had postbaseline data had treatment-emergent gp120 resistance-associated substitutions at 4 key sites (S375H/I/M/N/T, M426L/I, M434I/L, and 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 nonrandomized 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 value prior to discontinuation, or >1 log10 copies/mL increase in HIV-1 RNA at any time above the nadir level (≥40 copies/mL).

Robust CD4+ T-cell recovery approaching 7 years1*

Increase in CD4+ T-cells with RUKOBIA + OBT (Observed Analysis)

Results are descriptive.

Line graph showing CD4 T-cell mean change from baseline for RUKOBIA plus OBT for randomized cohort.

These results should not be used to infer clinical significance.

The Observed Analysis included only participants for whom CD4+ lab values were measured at each study visit, potentially favoring patients who benefited from treatment.3

*Based on BRIGHTE 336-week data.

Increase in CD4+ T-cells with RUKOBIA + OBT
(Observed Analysis, exploratory endpoint)

Results are descriptive.

Line graph showing CD4 T-cell mean change from baseline for RUKOBIA plus OBT for nonrandomized cohort.

These results should not be used to infer clinical significance.

The Observed Analysis included only participants for whom CD4+ lab values were measured at each study visit, potentially favoring patients who benefited from treatment.3

*Based on BRIGHTE 336-week data.

Robust CD4+ T-cell recovery across all subgroups2,4

Increase in CD4​+ T-cells with RUKOBIA + OBT through ~5 years (randomized cohort, Observed Analysis)

Line graph showing mean change from baseline in CD4 T-cell counts across subgroups.
  • The Observed Analysis included only participants for whom CD4+ lab values were measured at each study visit, potentially favoring treatment successes3
  • All participant subgroups categorized by baseline CD4+ T-cell count experienced a mean CD4+ T-cell increase by Week 240, based on a subgroup analysis​2

Results are descriptive.

*At Week 240, 19 participants did not have their data included in this analysis due to the impact of COVID-19.2

CD4+ T-cell counts ≥200 cells/mm3 in the majority of participants through ~5 years (observed analysis)2,8

CD4+ T-cell counts ≥200 cells/mm3 with RUKOBIA + OBT (randomized cohort, Observed Analysis)

Bar graph showing CD4 T-cell counts from baseline through Week 240.
  • The Observed Analysis included only individuals for whom CD4+ lab values were measured at each study visit, potentially favoring treatment successes2

Results are descriptive.

View the safety data for RUKOBIA

Safety profile

3TC=lamivudine; AIDS=acquired immunodeficiency syndrome; ARV=antiretroviral; BID=twice daily; CI=confidence interval; DRV=darunavir; DTG=dolutegravir; ENF=enfuvirtide; ETR=etravirine; FTC=emtricitabine; gp120=glycoprotein 120; HIV-1=human immunodeficiency virus type-1; IBA=ibalizumab; ITT–E=intent-to-treat–exposed; MDR=multidrug-resistant; MVC=maraviroc; OBT=optimized background therapy; PDVF=protocol-defined virologic failure; PI=prescribing information; RNA=ribonucleic acid; TDF=tenofovir disoproxil fumarate; TFV=tenofovir; VF=virologic failure.

References:

  1. Aberg JA, Mendo Urbina F, Katlama C, et al. 7-year sustained efficacy, safety, and immunological improvement with fostemsavir-based regimens in individuals with HIV and limited treatment options. Poster presented at: 20th European AIDS Conference; October 15-18, 2025; Paris, France. Poster eP125.
  2. Aberg JA, Shepherd B, Wang M, et al. Week 240 efficacy and safety of fostemsavir plus optimized background therapy in heavily treatment-experienced adults with HIV-1. Infect Dis Ther. 2023;12(9):2321-2335. doi:10.1007/s40121-023-00870-6
  3. Kozal M, Aberg J, Pialoux G, et al. Fostemsavir in adults with multidrug-resistant HIV-1 infection. N Engl J Med. 2020;382(13):1232-1243.
  4. 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 presented at: 24th International AIDS Conference; July 29–August 2, 2022; Montreal, Canada. Poster EPB160.
  5. Ackerman P, Wilkin T, Pierce A, et al. Clinical impact of antiretroviral agents used in optimized background therapy with fostemsavir in heavily treatment-experienced adults with HIV-1: exploratory analyses of the phase 3 BRIGHTE study. Presented at: 11th IAS Conference on HIV Science; July 18-21, 2021; Virtual. Poster PEB155.
  6. 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):e740-e751. doi:10.1016/S2352-3018(20)30240-X
  7. 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.
  8. Data on file, ViiV Healthcare.

PMUS-FSTWCNT260001