Clinical trial design and efficacy results for RUKOBIA (fostemsavir)

BRIGHTE: a ~5-year, Phase 3 trial with 371 participants living with MDR HIV-1¹

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-1.¹ 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.

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.¹

BRIGHTE trial design²

Schematic of the BRIGHTE phase 3, international, double-blind, placebo-controlled efficacy and safety trial

Primary endpoint²

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

*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).²

In BRIGHTE, RUKOBIA was used in combination with other ARVs to optimize the ARV regimen^4,5

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

Common ARVs in the initial OBT for each cohort in BRIGHTE

Bar graphs showing commonly used antiretroviral drugs among BRIGHTE trial participants

3TC or FTC were 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.

^‡For the nonrandomized cohort, experimental ARVs other than RUKOBIA were assumed to be fully active.⁵

^§Based on the screening criteria for activity (according to screening and historical resistance measures).⁵

^‖Of these 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 protocol deviations.⁵

BRIGHTE included a broad range of people living with MDR HIV-1^2,5,6

Randomized
Nonrandomized

1 to 2 active ARV classes

Baseline characteristics for randomized cohort (n=272)

Graphic showing median age of 48, median viral load of 4.7 log10 copies/mL, median CD4+ T-cell count of 99.5 cells/mm3, and % of participants across sex and ethnicities

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

Graphic showing % of participants with baseline CD4+ counts of ≥200 cells/mm3, 20-199 cells/mm3, and 1-19 cells/mm3

Additional baseline characteristics for randomized cohort

Graphic showing 85% of participants had a history of AIDS and 52% had only 1 fully active and available ARV

^¶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)

Graphic showing median age of 50, median viral load of 4.3 log10 copies/mL, median CD4+ T-cell count of 41 cells/mm3, and % of participants across sex and ethnicities

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

Additional baseline characteristics for nonrandomized cohort

Graphic showing 90% of participants had a history of AIDS and 19% had only 1 fully active and available ARV

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

^#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 protocol deviations.³

Superior antiviral activity at Day 8

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

Bar graph comparing efficacy of RUKOBIA + failing regimen to placebo + failing regimen

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

Virological response (HIV-1 RNA <40 copies/mL) for RUKOBIA + OBT through ~5 years (randomized cohort)

Results are descriptive.

Line graph showing long-term responses to RUKOBIA across varying analysis parameters in the randomized cohort

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 Analysis⁵

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

^†At Week 240, 12 participants (7 in the randomized cohort and 5 in the nonrandomized cohort) had completed the study by transitioning to locally approved fostemsavir (the first fostemsavir approval was in the US in July 2020).¹

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

Results are descriptive.

Line graph showing long-term responses to RUKOBIA across varying analysis parameters in the nonrandomized cohort

At Week 240, 5 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 Analysis⁵

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 Analysis⁵

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), 15 participants received ibalizumab, an investigational agent, at the start of BRIGHTE, and 4 patients were incorrectly assigned to the nonrandomized cohort.²

^§At Week 240, 12 participants (7 in the randomized cohort and 5 in the nonrandomized cohort) had completed the study by transitioning to locally approved fostemsavir (the first fostemsavir approval was in the US in July 2020).¹

Virologic suppression across subgroups^1,7

Randomized (N=272)
Nonrandomized (N=99)

Virologic response with RUKOBIA + OBT at ~5 years by subgroups⁵

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)

Virologic failure over time by Snapshot Analysis (ITT–E)¹

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 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.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)

*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).

No fully active ARV agents^†

Virologic response with RUKOBIA + OBT at ~5 years by subgroups (exploratory analysis)⁷

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)

Virologic failure over time by Snapshot Analysis (ITT–E)¹

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)

^†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.²

^‡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 across all subgroups^1,3

Increase in CD4⁺ T-cells with RUKOBIA + OBT through ~5 years (randomized cohort, observed analysis)

Line graph showing change in number of CD4+ T-cells for BRIGHTE participants with varied initial cell counts

Results are descriptive.

The observed analysis included only participants for whom CD4⁺ lab values were measured at each study visit, potentially favoring treatment successes²

All participant subgroups categorized by baseline CD4⁺ T-cell count experienced a mean CD4⁺ T-cell increase by Week 240, based on a subgroup analysis¹

*At Week 240, 19 participants did not have their data included in this analysis due to the impact of COVID-19.¹

CD4⁺ T-cell counts ≥200 cells/mm³ in the majority of participants through ~5 years (observed analysis)^1,7

CD4⁺ T-cell counts ≥200 cells/mm³with RUKOBIA + OBT (randomized cohort, observed analysis)

Bar graph showing % of participants with CD4+ T-cell counts above the CD4+ T-cell counts ≥ 200 cells/mm3 at baseline and Weeks 96 & 240

The observed analysis included only individuals for whom CD4⁺ lab values were measured at each study visit, potentially favoring treatment successes²

Robust CD4⁺ T-cell recovery despite no fully active and approved ARV agents in OBT¹

Increase in CD4⁺ T-cells from baseline with RUKOBIA + OBT through  ~5 years (nonrandomized cohort, exploratory analysis; results are descriptive)^1†

Line graph showing long-term mean change in CD4+ T-cell counts for BRIGHTE participants

^‡At Week 240, 5 participants did not have their data included in this analysis due to the impact of COVID-19.¹

Transcript

VISUAL: The opening screen fades in followed by a subtle movement to the top graphic (a few lines move slowly and the brightness of a few dots gently pulsates). One second later, the RUKOBIA logo fades in at the middle of the screen along with the ViiV logo. The top graphic continues to animate subtly. The RUKOBIA logo zooms out to the left as our 240-Week BRIGHTE Trial line crosses the screen from left to right.

MUSIC: Clinical-sounding ambient music plays in the background.

Key External Expert (KEE) VO: Indication. RUKOBIA, used with other antiretrovirals, is indicated for heavily treatment-experienced adults with multidrug-resistant HIV-1 who are failing their current ARV regimen. Important Safety Information. Contraindications. Do not use in patients with previous hypersensitivity to fostemsavir or any of the components of RUKOBIA. Do not use RUKOBIA in patients receiving strong cytochrome P450 (CYP)3A inducers, including those listed here. Please see additional Important Safety Information for RUKOBIA at the end of the video. Please click the link on this page to view the full Prescribing Information for RUKOBIA.

VISUAL: INDICATION and ISI fade on screen.

KEE VO: Hello, I’m doctor Tony Mills and I’m the founder and CEO of Men’s Health Foundation.

VISUAL: 240-Week BRIGHTE Trial graphic fades to video of KEE. Nameplate to accompany KEE with credentials. The graphic zooms out to top left position of the frame and our KEE fades in. The KEE’s name bumper starts to slide in frame from right to left.

KEE VO: I am excited to share the 5-year data from the RUKOBIA BRIGHTE trial for people living with multidrug-resistant HIV-1. RUKOBIA, as part of an optimized antiretroviral regimen, is the only antiretroviral therapy specifically developed for people living with multidrug-resistant HIV-1 clinically proven to offer virologic suppression and CD4 T-cell recovery over a 5-year trial. This long-term efficacy data reinforces the durability of RUKOBIA in many people living with multidrug-resistant HIV-1.

VISUAL: KEE speaking. Nameplate to accompany KEE with credentials.

KEE VO: As we know, people living with multidrug-resistant HIV-1 have a number of concerns and goals. These include lowering the viral load to stay undetectable, increasing CD4⁺ T-cell count for short- and long-term health, and finding a treatment with a manageable tolerability profile.

VISUAL: “Lower Viral Load,” “Increase CD4⁺ T-cell Count,” “Address Tolerability Concerns” populate as they are read.

KEE VO: In a moment, we’ll review the long-term data from the BRIGHTE trial. First, let’s take a look at the trial design.

VISUAL: Section opening for trial design. Title slide fades in. The top graphic continues to animate subtly. Copy on screen fades in with a one-second delay.

KEE VO: BRIGHTE was a Phase 3, international, partially randomized trial designed to evaluate the efficacy and safety of RUKOBIA. The trial included 371 participants representing a broad range of people living with multidrug-resistant HIV-1. All participants were on failing antiretroviral regimens and had multidrug resistance. In the randomized cohort, there were 272 participants who had 1 to 2 antiretroviral classes remaining at baseline. Through Day 8, this cohort was double blind and placebo controlled. Beyond Day 8, all randomized participants received open-label RUKOBIA in addition to an individualized optimized background therapy. Additionally, there were 99 participants in the nonrandomized cohort at baseline who had 0 fully active antiretroviral agents remaining and were allowed to co-enroll into other investigational antiretroviral trials. Participants in the BRIGHTE trial were studied over 5 years.

VISUAL: Graphic builds out three boxes.

KEE VO: The primary endpoint of the BRIGHTE trial was the adjusted mean plasma HIV-1 RNA log change from Day 1 to Day 8. RUKOBIA met the primary endpoint with superior viral load reductions versus placebo.

VISUAL: Primary endpoint description appears.

KEE VO: Now let’s take a look at the long-term data for RUKOBIA derived from the 272 participants in the randomized cohort.

VISUAL: Title slide fades in. The top graphic continues to animate subtly. Copy on screen fades in with a one-second delay.

KEE VO: RUKOBIA demonstrated durable virologic suppression over 5 years. 45% of participants receiving RUKOBIA, who were previously unable to construct a successful regimen, remained virologically suppressed over 5 years in the Snapshot Analysis. The Snapshot Analysis included the entire intent-to-treat–exposed population, which received at least 1 dose of treatment. Any missing data or change in optimized background therapy was counted as virologic failure.

VISUAL: Snapshot Analysis data builds.

KEE VO: At Week 240, it’s important to note that 19 participants, which is 7% of the Snapshot Analysis, were unable to have their HIV-1 RNA values assessed due to the impact of COVID-19 and therefore counted as virologic failures.

VISUAL: Ongoing COVID impact area is shown in shaded area on graph.

KEE VO: Durable virologic suppression was also seen in the Observed Analysis, where 82% of participants taking RUKOBIA remained virologically suppressed over 5 years. The Observed Analysis includes only participants for whom HIV-1 RNA values were measured at each study visit.

VISUAL: Observed Analysis data builds.

KEE VO: RUKOBIA also demonstrated robust and sustained CD4⁺ T-cell recovery across all baseline CD4⁺ T-cell subgroups over the 5 years. Mean CD4⁺T-cell counts improved from baseline over time, and increased by 296 cells per cubic millimeter at Week 240. Interestingly, the subgroup with the lowest baseline count experienced the greatest mean CD4⁺ T-cell increase.

VISUAL: CD4⁺ T-cell recovery graph slowly builds.

KEE VO: Now let’s take a look at a summary of the safety data from the BRIGHTE trial, which includes both the randomized and nonrandomized cohorts.

VISUAL: Title slide fades in. The top graphic continues to animate subtly. Copy on screen fades in with a one-second delay.

KEE VO: Over 5 years, 8 percent or 30 participants discontinued due to an adverse event. Of these, 3 percent or 12 participants discontinued due to infections, the most common adverse event leading to discontinuation.

VISUAL: Safety table builds.

KEE VO: The most frequent Grade 2-4 drug-related adverse events occurring in at least 2% of participants were nausea, diarrhea, headache, and immune reconstitution inflammatory syndrome.

VISUAL: Copy appears onscreen.

KEE VO: Thank you for your interest in the long-term data for RUKOBIA. As we know, people living with MDR HIV-1 often have complex needs. In this video, we’ve seen that over 5 years RUKOBIA demonstrated durable virologic suppression...

VISUAL: “THROUGH ~5 YEARS* DURABLE VIROLOGIC SUPPRESSION” appears next to the KEE.

KEE VO: ...and robust CD4⁺ T-cell recovery, helping you to confidently prescribe for this population.

VISUAL: “THROUGH ~5 YEARS* ROBUST CD4⁺ T-CELL RECOVERY” appears next to the KEE.

KEE VO: What can this long-term data for RUKOBIA mean for people living with multidrug-resistant HIV-1? As we know, this population requires an individualized approach to treatment. Now, with data over 5 years, creating a new regimen with RUKOBIA as the foundation may offer the stability that they need.

VISUAL: Shot of KEE with RUKOBIA logo and 240-Week BRIGHTE Trial line.

KEE VO: Important Safety Information, continued. Warnings and Precautions. Immune Reconstitution Syndrome and autoimmune disorders have been reported with the use of RUKOBIA. QTc prolongation has occurred with higher than recommended dosages of RUKOBIA. Use RUKOBIA with caution in patients with a history of QTc interval prolongation or cardiac disease, or who are taking drugs with a known risk of Torsade de Pointes. Elderly patients may be more susceptible. Monitoring of liver chemistries is recommended in patients with hepatitis B and/or C co-infection. Diligence should be applied when starting RUKOBIA in patients receiving hepatitis B therapy. Adverse reactions or loss of virologic response due to drug interactions may occur when using RUKOBIA with other drugs. Adverse Reactions. The most common adverse reaction reported with RUKOBIA was nausea.

Drug Interactions. See the full Prescribing Information for RUKOBIA for all significant drug interactions. Temsavir may increase plasma concentrations of grazoprevir and voxilaprevir. Use an alternative hepatitis C virus regimen, if possible. Use the lowest possible starting dose for statins with careful monitoring. Patients receiving RUKOBIA should not take estrogen-based therapies that contain more than 30 micrograms per day of ethinyl estradiol. Use RUKOBIA with caution in patients with additional risk factors for thromboembolic events. Use in Specific Populations. There are insufficient data on the use of RUKOBIA during pregnancy to assess drug-associated risks. Breastfeeding is not recommended in patients with HIV-1. Please click the link on this page to view the full Prescribing Information for RUKOBIA.

VISUAL: Important Safety Information fades in and begins scrolling, pace keeping in time with VO.

KEE VO: N/A

SUPERS:

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 presented at: 24th International AIDS Conference; July 29-August 2, 2022; Montreal, Canada.
Data on file, ViiV Healthcare.
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.
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.
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.

VISUAL: References appear.

MUSIC: Clinical-sounding ambient music plays in the background.

KEE VO: N/A

VISUAL: Brand colors fade in. Call-to-action, logo, and sign-off appear with a one-second delay.

MUSIC: Clinical-sounding ambient music plays in the background and then stops.

Dr. Tony Mills reviews exciting long-term data for RUKOBIA

BRIGHTE Long-Term Data

The BRIGHTE study provides ~5-year efficacy results¹

View the ~5-year 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:

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
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.
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.
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.
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
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.
Data on file, ViiV Healthcare.

FSTWCNT230025

INDICATION

RUKOBIA, in combination with other antiretrovirals (ARVs), is indicated to treat HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current ARV regimen due to resistance, intolerance, or safety considerations.

IMPORTANT SAFETY INFORMATION

Contraindications

Do not use in patients with previous hypersensitivity to fostemsavir or any of the components of RUKOBIA.
Do not use RUKOBIA in patients receiving strong cytochrome P450 (CYP)3A inducers, including but not limited to enzalutamide, carbamazepine, phenytoin, rifampin, mitotane, and St John’s wort (Hypericum perforatum).

INDICATION

IMPORTANT SAFETY INFORMATION

Contraindications

Do not use in patients with previous hypersensitivity to fostemsavir or any of the components of RUKOBIA.
Do not use RUKOBIA in patients receiving strong cytochrome P450 (CYP)3A inducers, including but not limited to enzalutamide, carbamazepine, phenytoin, rifampin, mitotane, and St John’s wort (Hypericum perforatum).

Warnings and precautions

Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of RUKOBIA.

QTc Prolongation with Higher than Recommended Dosages: RUKOBIA at 2,400 mg twice daily has been shown to significantly prolong the QTc interval of the electrocardiogram. Use RUKOBIA with caution in patients with a history of QTc interval prolongation or in patients with relevant pre-existing cardiac disease or who are taking drugs with a known risk of Torsade de Pointes. Elderly patients may be more susceptible to drug-induced QT interval prolongation.

Elevations in Hepatic Transaminases in Patients with Hepatitis B or C Virus Co-infection:

Monitoring of liver chemistries is recommended in patients with hepatitis B and/or C co-infection.
Diligence should be applied in initiating or maintaining effective hepatitis B therapy when starting RUKOBIA in patients co-infected with hepatitis B.

Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of RUKOBIA and other drugs may occur (see Contraindications and Drug Interactions).

Adverse reactions

The most common adverse reaction (all grades, randomized cohort) observed in ≥5% of subjects was nausea (10%).
81% of adverse reactions reported with RUKOBIA were mild or moderate in severity.

Drug interactions

See the full Prescribing Information for RUKOBIA for a complete list of significant drug interactions.
Temsavir may increase plasma concentrations of grazoprevir and voxilaprevir. Use an alternative hepatitis C virus regimen if possible.
Use the lowest possible starting dose for statins and monitor for statin-associated adverse events.
Patients receiving RUKOBIA should not take doses of estrogen-based therapies, including oral contraceptives, that contain more than 30 mcg/day of ethinyl estradiol. Caution is advised particularly in patients with additional risk factors for thromboembolic events.

Use in specific populations

Pregnancy: There are insufficient human data on the use of RUKOBIA during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established.
Lactation: Potential risks of breastfeeding include HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant.

Please see full Prescribing Information for RUKOBIA.

FSTWCNT230034

Trademarks are owned by or licensed to the ViiV Healthcare group of companies.

This site is funded and developed by ViiV Healthcare.

This site is intended for US healthcare professionals only.

FSTWCNT230032 December 2023

Produced in USA.

Clinical trial design and efficacy results for RUKOBIA (fostemsavir)

BRIGHTE: a ~5-year, Phase 3 trial with 371 participants living with MDR HIV-11

BRIGHTE trial design2

Primary endpoint2

In BRIGHTE, RUKOBIA was used in combination with other ARVs to optimize the ARV regimen4,5

Common ARVs in the initial OBT for each cohort in BRIGHTE

BRIGHTE included a broad range of people living with MDR HIV-12,5,6

Baseline characteristics for randomized cohort (n=272)

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

Additional baseline characteristics for randomized cohort

Baseline characteristics for nonrandomized cohort (n=99)

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

Additional baseline characteristics for nonrandomized cohort

Superior antiviral activity at Day 8

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

Rates of virologic suppression1,5,7

Virological response (HIV-1 RNA <40 copies/mL) for RUKOBIA + OBT through ~5 years (randomized cohort)

Included in the Snapshot Analysis5

Included in the Observed Analysis5

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

Included in the Snapshot Analysis5

Included in the Observed Analysis5

Virologic suppression across subgroups1,7

Virologic response with RUKOBIA + OBT at ~5 years by subgroups5

Virologic failure over time by Snapshot Analysis (ITT–E)1

Protocol-defined VF with RUKOBIA + OBT

Virologic response with RUKOBIA + OBT at ~5 years by subgroups (exploratory analysis)7

Virologic failure over time by Snapshot Analysis (ITT–E)1

Protocol-defined VF with RUKOBIA + OBT

Robust CD4+ T-cell recovery across all subgroups1,3

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

CD4+ T-cell counts ≥200 cells/mm3 in the majority of participants through ~5 years (observed analysis)1,7

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

Robust CD4+ T-cell recovery despite no fully active and approved ARV agents in OBT1

Increase in CD4+ T-cells from baseline with RUKOBIA + OBT through ~5 years (nonrandomized cohort, exploratory analysis; results are descriptive)1†

Dr. Tony Mills reviews exciting long-term data for RUKOBIA

BRIGHTE Long-Term Data

View the ~5-year safety data for RUKOBIA

INDICATION

IMPORTANT SAFETY INFORMATION

Contraindications

INDICATION

IMPORTANT SAFETY INFORMATION

Contraindications

Warnings and precautions

Adverse reactions

Drug interactions

Use in specific populations

BRIGHTE: a ~5-year, Phase 3 trial with 371 participants living with MDR HIV-1¹

BRIGHTE trial design²

Primary endpoint²

In BRIGHTE, RUKOBIA was used in combination with other ARVs to optimize the ARV regimen^4,5

BRIGHTE included a broad range of people living with MDR HIV-1^2,5,6

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

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

Rates of virologic suppression^1,5,7

Included in the Snapshot Analysis⁵

Included in the Observed Analysis⁵

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

Included in the Snapshot Analysis⁵

Included in the Observed Analysis⁵

Virologic suppression across subgroups^1,7

Virologic response with RUKOBIA + OBT at ~5 years by subgroups⁵

Virologic failure over time by Snapshot Analysis (ITT–E)¹

Virologic response with RUKOBIA + OBT at ~5 years by subgroups (exploratory analysis)⁷

Virologic failure over time by Snapshot Analysis (ITT–E)¹

Robust CD4⁺ T-cell recovery across all subgroups^1,3

Increase in CD4⁺ T-cells with RUKOBIA + OBT through ~5 years (randomized cohort, observed analysis)

CD4⁺ T-cell counts ≥200 cells/mm³ in the majority of participants through ~5 years (observed analysis)^1,7

CD4⁺ T-cell counts ≥200 cells/mm³with RUKOBIA + OBT (randomized cohort, observed analysis)

Robust CD4⁺ T-cell recovery despite no fully active and approved ARV agents in OBT¹

Increase in CD4⁺ T-cells from baseline with RUKOBIA + OBT through  ~5 years (nonrandomized cohort, exploratory analysis; results are descriptive)^1†