VISUAL: CABENUVA and ViiV logos, series title, and video title animate on screen over Dr Hsu and then move off screen.
SUPER:
Expert Perspectives: Conversations on CABENUVA
CABENUVA: From Clinical Trials to Real-World Application
[ViiV Healthcare logo]
[CABENUVA Logo on screen for entire video]
VISUAL: Speaker on screen; graphics animate on screen.
SUPER:
Ricky K. Hsu, MD
compensated by ViiV Healthcare
Dr Hsu: Hello, my name is Dr Ricky Hsu.
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SUPER:
Ricky K. Hsu, MD
Principal Investigator of the OPERA study and National Medical Director of the AIDS Healthcare Foundation
Dr Hsu: I am board certified in Internal Medicine…
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SUPER:
Ricky K. Hsu, MD
Adjunct Professor of Medicine at the New York University School of Medicine
Dr Hsu: … and certified as an HIV Specialist.
VISUAL: Speaker on screen.
Dr Hsu: I’ve been in practice for almost 30 years. My clinical practice consists of roughly 1000 HIV-positive patients of a variety of ethnicities in an urban setting. We see patients who range from newly diagnosed with HIV to those who are long-term HIV survivors.
Please join me for a discussion on the SOLAR clinical trial and data from OPERA that observed the use of CABENUVA in real-world settings. Before we begin, let us review some Important Safety Information for CABENUVA.
VISUAL: Indication and Contraindications animate on screen.
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INDICATION
CABENUVA is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
- Do not use CABENUVA in patients with previous hypersensitivity reaction to cabotegravir or rilpivirine
- Do not use CABENUVA in patients receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone (>1 dose), and St John’s wort
Please watch the entire video for additional Important Safety Information.
Please click the link to view the Prescribing Information for CABENUVA.
Narrator: CABENUVA is for virologically suppressed adults and adolescents with HIV-1 who meet certain requirements. See full indication on screen.
It is contraindicated in patients with a previous hypersensitivity reaction to cabotegravir or rilpivirine and in patients receiving the medications listed here.
Please watch the entire video for additional Important Safety Information.
Please click the link to view the Prescribing Information for CABENUVA.
VISUAL: Speaker on screen; split screen graphic animates on left-hand side.
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Clinical Trial and Real-World Evidence Overview
Dr Hsu: Let’s begin our discussion with an overview of CABENUVA's clinical trial program and real-world evidence collected in the United States.
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Dr Hsu: CABENUVA’s development has been supported by a robust phase 3/3b clinical trial program, which led to the approval of the once-monthly and then every-2-month dosing regimens for CABENUVA.
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SUPER:
Randomized Clinical Trials
Pivotal Trials
ATLAS (N=616) & FLAIR (N=566): Once-monthly CABENUVA vs Daily oral ART
ATLAS-2M (N=1045): Every-2-month CABENUVA vs Once-monthly CABENUVA
SOLAR (N=681): Every-2-month CABENUVA vs Once-daily BIKTAVY
Real-World Studies
OPERA (N=1362): Observational study of US adults after a switch to CABENUVA or a new oral therapy
BEYOND (N=233): Ongoing, prospective, observational study of US adults switching to CABENUVA
Real-world studies are designed to complement clinical trial data, not definitively establish causality. Data may better reflect actual patient populations and clinical care. Data are susceptible to bias. Observational studies have the potential for missing, inaccurate, incomplete data, or overlapping data.
Dr Hsu: The pivotal ATLAS, FLAIR, and ATLAS-2M randomized clinical trials established the efficacy and safety of CABENUVA.
VISUAL: Full-screen image; SOLAR study design, primary endpoint graphic, exclusion criteria graphic, efficacy and safety analyses bullets and footnotes on screen. Key baseline characteristics animate on screen as Dr Hsu speaks.
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SOLAR is the first head-to-head switch study comparing every-2-month CABENUVA with continuing daily oral BIKTARVY
A large phase 3b, open-label, noninferiority study of virologically suppressed adults (greater than or equal to 18 years) with HIV-1
[Graphic showing the SOLAR study design]
Primary endpoint (mITT-E population)
- Proportion of patients with HIV-1 RNA ≥50 copies/mL in the Month 12 analysis
Exclusion criteria
- History of virologic failure
- Known or suspected presence of resistance mutations to the individual components of BIKTARVY or CABENUVA
- HBV infection at screening
- Moderate to severe hepatic impairment
- Women who were pregnant or breastfeeding or planned to become pregnant or breastfeed
Key baseline characteristics (CABENUVA arm)
- Median age (range): 37 (18-74) years
- Sex assigned at birth, female: 17%
- Race/Ethnicity, White: 69%, Black/African American: 21%, Hispanic or Latinx ethnicity: 21%
- Median (IQR) BMI: 26 kg/m2 (23-29)
- Median duration of prior BIKTARVY medication: 1.8 years
- Efficacy analyses, baseline questionnaire, and preference calculation were based on the mITT-E (N=670) After consultation with a blinded external expert, 11 participants at a single study site were excluded from the ITT-E population due to critical findings related to significant and persistent non-compliance to protocol requirements
- Safety analyses were based on ITT-E (N=681) population
Dr Hsu: The SOLAR study is a Phase 3b, open-label, noninferiority trial that compared switching virologically suppressed adult participants to every-2-month CABENUVA with continuing once-daily oral BIKTARVY. The primary endpoint was the proportion of participants who had greater than or equal to 50 copies per mL of HIV RNA at Month 12.
The efficacy analyses, baseline questionnaire, and preference calculation were based on a modified intent-to-treat population, mITT-E, which included 670 patients. In contrast, the safety analyses were based on the entire intent-to-treat population, ITT-E, which encompassed all 681 enrolled participants.
Let’s look at the baseline patient population in the SOLAR study. SOLAR included a broad range of participants. The median age of participants on CABENUVA was 37 years. Most participants were male, approximately 20% were female, and about 20% were Black or African American. The median duration of prior treatment with BIKTARVY in participants who switched to CABENUVA was 1.8 years.
VISUAL: Full-screen image; primary and secondary endpoint graphics, and footnotes on screen. CVF graphic animated on as Dr Hsu speaks.
SUPER:
SOLAR Every-2-month CABENUVA was noninferior to daily oral BIKTARVY and 90% of CABENUVA-treated participants maintained virologic suppression
The SOLAR primary endpoint was met (HIV-1 RNA ≥50 copies/mL): Every-2-month CABENUVA was noninferior to BIKTARVY at Month 12 analysis (mITT-E; 1% [5/447] vs <1% [1/223], respectively, adjusted difference=0.7% [95% CI, -0.7% to 2.0%]).
Secondary Endpoint (mITT-E population)
HIV-1 RNA <50 copies/mL at Month 12 analysis
[Bar chart comparing rates of virologic suppression between Every-2-month CABENUVA (n=403/447) and Once-daily BIKTARVY (n=207/223)]
CVF Through Month 12 Analysis
(2 consecutive HIV-1 RNA levels ≥200 copies/mL)
[Graphic showing percent of CABENUVA patients in CVF versus BIKTARVY patients in the SOLAR study]
- Of the two CVFs on CABENUVA, both patients had treatment-emergent RPV and INSTI RAMs observed
Patients who met CVF re-suppressed on alternative, highly suppressive antiretroviral therapies
- Key differences in ATLAS-2M: all patients had previously received an NNRTI-, PI-, or INSTI-based regimen. Through Week 152, there were 12 (2%) CVFs in the every-2-month arm and 2 (<1%) in the once-monthly arm
Dr Hsu: The SOLAR primary endpoint was met, demonstrating that every-2-month CABENUVA was noninferior to BIKTARVY through Month 12 analysis. The key secondary endpoint showed that the rates of virologic suppression were similar between both treatment arms. Confirmed virologic failure was defined as 2 consecutive HIV-1 RNA levels that were at least 200 copies per mL. 0.4%, or 2 participants, met CVF in the CABENUVA arm.
VISUAL: Split-screen image; SOLAR Safety Profile table, associated bullets, and footnotes animate on screen as Dr Hsu speaks.
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SOLAR Drug-related adverse events
[Table showing Drug-related AEs of Every-2-month CABENUA (n=454) compared to Once-daily BIKTARVY (n=227)]
- 2% of CABENUVA patients (event-level) discontinued treatment due to injection-related reasons, and 2% discontinued due to non-ISR, drug-related adverse events
- ISRs included pain (62%), nodule (9%), swelling (9%), discomfort (9%), and induration (7%)
Dr Hsu: Moving on to the CABENUVA safety profile, drug-related adverse events were more frequent in the CABENUVA arm. But this is not a surprise to me since this is a switch study, where participants had entered the study already virologically suppressed on and clinically acclimated to BIKTARVY.
The most common drug-related adverse events in the CABENUVA arm were injection-site reactions, which is consistent with findings from previous studies. Furthermore, the discontinuation rate due to drug-related adverse events in the CABENUVA arm was 4%.
VISUAL: Split-screen: ISR bar graph, associated copy, and footnotes animate on screen as Dr Hsu speaks.
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SOLAR Participants-reported ISRs decreased over time
Incidence of reported ISRs (all grades) by visit
[Bar graph showing how participant-reported ISRs decreased over time]
Self-reported ISRs could potentially underestimate the true rate of ISRs over time. ISRs may still be present but not reported during the study.
Majority of ISR events (event-level: 98% [1885/1915]) were grades 1-2. The median (IQR) duration of ISR events was 3 (2,5) days.
Dr Hsu: Notably, injection-site reactions decreased over time with the majority of ISRs graded as mild to moderate in severity. However, self-reported ISRs could potentially underestimate the true rate of ISRs over time, as ISRs may still be present but not reported during the study.
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Real-World Evidence: Study Design and Outcomes
Dr Hsu: Let’s start our discussion about the OPERA real-world study.
It is important to note that real-world studies are designed to complement clinical trial data, not definitively establish causality. The results are descriptive.
VISUAL: Full-screen image; OPERA study design, bullet, endpoints, and footnotes on screen. Censoring criteria animates on screen as Dr Hsu speaks.
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OPERA is a real-world study of adult participants who switched to CABENUVA or a new oral ART regimen
OPERA includes routine clinical data from electronic health records from 101 clinics across 23 US states and territories
[Graphic showing the OPERA study design]
Endpoints
- Virology outcomes among those with at least 1 follow-up HIV-1 RNA available
- HIV-1 RNA <50 copies/mL
- CVF
Censoring criteria
- Discontinuation of ART regimen of interest
- Death
- 12 months after last clinical contact
- End of analysis period June 30, 2023
- Overall, the OPERA database represents ~14% of people with HIV in the US
Dr Hsu: OPERA is an observational real-world study of adult participants who switched to CABENUVA or a new oral antiretroviral therapy. The data came from electronic health records from 101 clinics across 23 US states and territories. The OPERA database represents approximately 14% of people living with HIV across the United States.
Key endpoints included virologic outcomes among those with at least 1 follow-up viral load available.
Key censoring criteria included discontinuation of the ART regimen of interest, death, if it’s been 12 months after last clinical contact, and end of analysis period on June 30, 2023.
VISUAL: Full-screen image; baseline participant characteristics table and footnotes animate on screen as Dr Hsu speaks.
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OPERA is a real-world study comparing adult participants who switched to CABENUVA or a new oral ART regimen
Demographics and baseline characteristics
[Table showing baseline characteristics of the OPERA study, comparing CABENUVA arm (N=1362) versus Oral ART (N=2783)]
Dr Hsu: Now, let’s jump into the baseline participant characteristics of the OPERA study.
The median age of participants who switched to CABENUVA was 39 years. Most of the participants were male, 17% were female, 41% were Black, and 29% were of Hispanic ethnicity in the CABENUVA arm.
In addition, most participants treated with CABENUVA switched from an INSTI-based regimen and had been on an antiretroviral regimen for a median of 20 months prior to study enrollment. Median duration of follow-up for participants receiving CABENUVA was 11 months compared to 17 months for those receiving a new oral ART regimen.
VISUAL: Full-screen image; bar graph and associated bullet on-screen. CVF graphic, associated bullets, and footnotes animate on screen as Dr Hsu speaks.
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OPERA Switching to CABENUVA showed similarly high rates of maintaining virologic suppression vs a new daily oral therapy
Rate of maintaining virologic suppression
[Bar chart showing rate of maintaining virologic suppression of CABENUVA (n=1229/1293) versus New Oral ART (n=2298/2523)]
Similar rate of CVF observed between participants switching to CABENUVA or a new oral therapy (adjusted OR [95% CI]=0.64 [0.40 to 1.02])
[Graphic showing percent of CABENUVA patients in CVF versus BIKTARVY patients in the OPERA study]
CVF was defined as 2 HIV-1 RNA measurements ≥200 copies/mL or 1 HIV-1 RNA ≥200 copies/mL plus discontinuation.
- Following CVF, patients in each group had similar rates of virologic re-suppression
- The most common regimens switched to were oral INSTI-based regimens
- No safety or discontinuation data reported
Real-world studies are designed to evaluate associations among variables and not to definitively establish causality. These results are descriptive.
Dr Hsu: The efficacy of CABENUVA observed in OPERA reinforces the results seen in prospective clinical trials. Among those with a follow-up viral load available, 95% of participants who switched to CABENUVA maintained virologic suppression and 91% maintained virologic suppression on oral ART.
In addition, there was no difference between the arms in the rate of meeting the definition of CVF. 2% of participants treated with CABENUVA and 3% of participants treated with a new oral ART regimen met the CVF criteria, and the most common regimens switched to after CVF were oral INSTI-based regimens. Following CVF, participants receiving CABENUVA had a similar rate of virologic resuppression to those treated with oral ART.
These findings reinforce my belief in CABENUVA as a safe and efficacious regimen as demonstrated in pivotal trials. However, I think it’s also important to note that real-world studies are designed to evaluate associations among variables and not to definitively establish causality.
VISUAL: Split-screen image; icons and text animate on screen as Dr Hsu speaks.
SUPER:
Today we discussed:
Proven efficacy
Noninferior vs daily oral therapy with BIKTARVY in SOLAR
Real-world data
From OPERA reinforced the efficacy of CABENUVA seen in prospective studies
Real-world application
Encourage a shared decision-making approach to decide if CABENUVA is the right fit for them
Dr Hsu: To summarize our conversation today, we discussed that the SOLAR study showed that every-2-month CABENUVA was noninferior to continuing daily oral BIKTARVY. In addition, real-world data from OPERA reinforced the efficacy of CABENUVA seen in prospective studies.
These studies reflect my experience in clinical practice with CABENUVA. I hope that clinicians will proactively offer CABENUVA as an option to appropriate patients. I feel that shared decision-making in HIV care is essential.
VISUAL: Speaker on-screen. Graphic animates on as Dr Hsu speaks.
SUPER: Continue watching for additional Important Safety Information.
Dr Hsu: On behalf of ViiV Healthcare, I would like to thank you for taking the time to learn more about CABENUVA clinical and real-world data. Continue watching for additional Important Safety Information.
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IMPORTANT SAFETY INFORMATION (cont’d)
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions:
- Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with CABENUVA
- Hypersensitivity reactions, including cases of drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during postmarking experience with rilpivirine-containing regimens. While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries
- Discontinue CABENUVA immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated. Cabotegravir and rilpivirine oral lead-in may be used to help identify patients who may be at risk of a hypersensitivity reaction
Post-Injection Reactions:
- Serious post-injection reactions (reported in less than 1% of subjects) were reported within minutes after the injection of rilpivirine, including dyspnea, bronchospasm, agitation, abdominal cramping, rash/urticaria, dizziness, flushing, sweating, oral numbness, changes in blood pressure, and pain (e.g., back and chest). These events may have been associated with accidental intravenous administration and began to resolve within a few minutes after the injection
Narrator: WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions: Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and during postmarketing experience with rilpivirine-containing regimens where reactions include cases of drug reaction with eosinophilia and systemic symptoms. Some skin reactions were accompanied by symptoms such as fever, other skin reactions were associated with organ dysfunctions. Oral lead-in may be administered prior to administration of CABENUVA to help identify patients who may be at risk for a hypersensitivity reaction. If a hypersensitivity reaction is suspected, CABENUVA should be discontinued immediately, and the patient should be monitored.
Post-Injection Reactions: In clinical trials, serious post-injection reactions, such as those shown here, were reported in less than 1% of subjects within minutes after the injection of rilpivirine. These events may have been a result of accidental IV administration and began to resolve within a few minutes after the injection.
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IMPORTANT SAFETY INFORMATION (cont’d)
WARNINGS AND PRECAUTIONS (cont’d)
Post-Injection Reactions (cont’d):
- Carefully follow the Instructions for Use when preparing and administering CABENUVA. The suspensions should be injected slowly via intramuscular injection and avoid accidental intravenous administration. Observe patients briefly (approximately 10 minutes) after the injection. If a post-injection reaction occurs, monitor and treat as clinically indicated
Hepatotoxicity:
- Hepatotoxicity has been reported in patient receiving cabotegravir or rilpivirine with or without known pre-existing hepatic disease or identifiable risk factors
- Patients with underlying liver disease or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations
- Monitoring of liver chemistries is recommended and treatment with CABENUVA should be discontinued if hepatotoxicity is suspected
Depressive Disorders:
- Depressive disorders (including depressed mood, depression, major depression, mood altered, mood swings, dysphoria, negative thoughts, suicidal ideation, suicide attempt) have been reported with CABENUVA or the individual products
- Promptly evaluate patients with depressive symptoms
Narrator: It is important to carefully follow the instructions for use and observe patients for approximately 10 minutes after the injection. If a post-injection reaction occurs, monitor and treat as clinically indicated.
Hepatotoxicity: Hepatic adverse events have been reported in patients receiving cabotegravir or rilpivirine with or without pre-existing hepatic disease or identifiable risk factors. Patients with underlying liver disease prior to treatment may be at increased risk with CABENUVA. Hepatic monitoring is recommended and discontinue if hepatotoxicity is suspected.
Depressive Disorders: Depressive disorders have been reported with CABENUVA or the individual components; promptly evaluate patients with depressive symptoms.
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IMPORTANT SAFETY INFORMATION (cont’d)
WARNINGS AND PRECAUTIONS (cont’d)
Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions:
- The concomitant use of CABENUVA and other drugs may result in known or potentially significant drug interactions (see Contraindications and Drug Interactions)
- Rilpivirine doses 3 and 12 times higher than the recommended oral dosage can prolong the QTc interval
- CABENUVA should be used with caution in combination with drugs with a known risk of Torsade de Pointes
Long-Acting Properties and Potential Associated Risks with CABENUVA:
- Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer). Select appropriate patients who agree to the required monthly or every-2-month injection dosing schedule because non-adherence could lead to loss of virologic response and development of resistance
- To minimize the potential risk of developing viral resistance, it is essential to initiate an alternative, fully suppressive antiretroviral regimen no later than 1 month after the final injection doses of CABENUVA when dosed monthly and no later than 2 months after the final injections of CABENUVA when dosed every 2 months. If virologic failure is suspected, switch the patient to an alternative regimen as soon as possible
Narrator: Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions:
Adverse reactions or loss of virologic response due to drug interactions with concomitant use of CABENUVA may occur. Use with caution in combination with drugs with a known risk of Torsade de Pointes.
Long-Acting Properties and Potential Associated Risks with CABENUVA: Residual cabotegravir and rilpivirine concentrations may remain in the systemic circulation for up to 12 months or longer. Non-adherence to injections could lead to loss of virologic response and development of resistance. It is important to initiate a fully suppressive regimen no later than 1 month after the final injection doses of CABENUVA when dosed once-monthly and no later than 2 months after the final injections of CABENUVA when dosed every 2 months. If virologic failure is suspected, switch the patient to an alternative regimen as soon as possible.
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IMPORTANT SAFETY INFORMATION (cont’d)
ADVERSE REACTIONS
- The most common adverse reactions (incidence ≥2%, Grades 1 to 4) with CABENUVA were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash
DRUG INTERACTIONS
- Refer to the applicable full Prescribing Information for important drug interactions with CABENUVA, VOCABRIA (cabotegravir), or EDURANT (rilpivirine)
- Because CABENUVA is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended
- Drugs that are strong inducers of UGT1A1 or UGT1A9 are expected to decrease the plasma concentrations of cabotegravir. Drugs that induce or inhibit CYP3A may affect the plasma concentrations of rilpivirine
- CABENUVA should be used with caution in combination with drugs with a known risk of Torsade de Pointes
Narrator: ADVERSE REACTIONS
The most common adverse drug reactions were injection site reactions, pyrexia, fatigue, headache, and those listed here.
DRUG INTERACTIONS
For important drug interaction information, refer to the full Prescribing Information for CABENUVA, VOCABRIA for oral cabotegravir, and EDURANT for oral rilpivirine. It is not recommended to coadminister CABENUVA with other antiretrovirals. Drugs that are strong inducers of UGT1A1 or UGT1A9 are expected to decrease the plasma concentrations of cabotegravir. Drugs that induce or inhibit CYP3A may affect the plasma concentrations of rilpivirine.
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IMPORTANT SAFETY INFORMATION (cont’d)
USE IN SPECIFIC POPULATIONS
- Pregnancy: There are insufficient human data on the use of CABENUVA during pregnancy to adequately assess a drug-associated risk for birth defects and miscarriage. Discuss the benefit-risk of using CABENUVA during pregnancy and conception and consider that cabotegravir and rilpivirine are detected in systemic circulation for up to 12 months or longer after discontinuing injections of CABENUVA. 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 click the link to view the full Prescribing Information for CABENUVA.
Narrator: USE IN SPECIFIC POPULATIONS
Assess the potential risks of using CABENUVA during conception, pregnancy, and while breastfeeding.
Please click the link on this page to view the full Prescribing Information for CABENUVA.
VISUAL: Full-screen image animates on screen then fades to black.
SUPER:
Expert Perspectives: Conversations on CABENUVA
Interested in hearing from more experts?
Check out our other videos in the “Expert Perspectives: Conversations on CABENUVA” series
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PMUS-CBRVID240080 February 2025
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