For virologically suppressed individuals 12 years or older weighing at least 35 kg with HIV-1. See Full Indication.

Clinical Trial for Every-2-Month CABENUVA

ATLAS-2M, a large, Phase 3b trial demonstrating the noninferiority of CABENUVA administered every 2 months compared with once-monthly administration. Healthcare professionals are encouraged to explore the results in detail by accessing the information below.

ATLAS-2M Trial Design for CABENUVA

ATLAS-2M was a noninferiority clinical trial that evaluated the efficacy and safety of long-acting CABENUVA administered once monthly vs every 2 months in adult (≥18 years) patients with HIV-1 who were virologically suppressed at time of randomization.^1-3

The primary endpoint for the study was the proportion of patients with HIV-1 RNA ≥50 copies/mL at Week 48. Secondary endpoints included the proportion of patients with HIV-1 RNA ≥50 copies/mL at Week 96 and with HIV-1 RNA <50 copies/mL at Weeks 48 and 96.

Selected Exclusion Criteria³:

History of virologic failure
Any known INSTI or NNRTI resistance (excluding K103N)
Hepatitis B virus infection at screening
Moderate to severe hepatic impairment
Women who were pregnant, breastfeeding, or planned to become pregnant or breastfeed during the study

ATLAS-2M: Large, Phase 3, open-label noninferiority* study^2,3

ATLAS-2M TRIAL DESIGN^2,3

Virologically suppressed adults (≥18 years of age) with HIV-1

*Noninferiority of every-2-month CABENUVA would be shown if the upper bound of the 95% CI for the treatment difference was <4% at Week 48.² ^†Acceptable ARV regimens (either initial or second ARV regimen) included 2 NRTIs plus an INSTI, NNRTI, or boosted PI (or ATV unboosted).³ ^‡Patients were suppressed for ≥6 months, with suppression defined as HIV-1 RNA <50 copies/mL.³ ^§Patients transitioning from the ATLAS trial were on once-monthly CABENUVA or a current ARV regimen through at least 52 weeks and had plasma HIV-1 RNA <50 copies/mL.³ ^||Oral lead-in regimen consisted of 30-mg cabotegravir and 25-mg rilpivirine once daily given for 1 month (at least 28 days). ^¶Patients transitioning from the ATLAS trial with exposure to once-monthly CABENUVA received their first injections on Day 1.^{2 #}Initiation injections were administered on the last day of oral lead-in once for the monthly dosing schedule and for 2 consecutive months for the every-2-month dosing schedule.

ARV=antiretroviral; ATV=atazanavir; CI=confidence interval; INSTI=integrase strand transfer inhibitor; NNRTI=non-nucleoside reverse transcriptase inhibitor; NRTI=nucleoside reverse transcriptase inhibitor; PI=protease inhibitor.

ATLAS-2M included a broad range of patients

ATLAS-2M: BASELINE PATIENT CHARACTERISTICS²

At baseline, 7% of patients in the every-2-month arm and 5% of patients in the once-monthly arm had a CD4+ cell count <350 ²

**8 patients who were assigned male at birth identified as female at enrollment.²

IQR=interquartile range.

**8 patients who were assigned male at birth identified as female at enrollment.²

IQR=interquartile range.

Efficacy of Every-2-Month CABENUVA

Every-2-Month CABENUVA was proven as effective as once-monthly CABENUVA

Every-2-month CABENUVA was found to be noninferior to once-monthly CABENUVA (upper bound of 95% CI for the treatment difference was <4%) at Weeks 48 and 96.^2,3

ATLAS-2M: ITT-E FDA SNAPSHOT VIROLOGIC OUTCOMES THROUGH WEEK 96^2,3

No virologic data at Week 48: 4% (21/522) in every-2-month CABENUVA; 6% (29/523) in once-monthly CABENUVA²
No virologic data at Week 96: 7% (36/522) in every-2-month CABENUVA; 9% (45/523) in once-monthly CABENUVA³

*Primary endpoint: HIV-1 RNA ≥50 copies/mL at Week 48. ^†Secondary endpoints: HIV-1 RNA <50 copies/mL at Week 48 and at Week 96, and HIV-1 RNA ≥50 copies/mL at Week 96.^2,3

FDA=Food and Drug Administration; ITT-E=intent-to-treat efficacy.

Confirmed Virologic Failure

Low incidence of confirmed virologic failure in both treatment arms

One out of the ten confirmed virologic failures (CVF) was observed between Week 48 and 96 in a patient receiving every-2-month CABENUVA.³

ATLAS-2M: CONFIRMED VIROLOGIC FAILURE THROUGH WEEK 96³

1 patient in the every-2-month CABENUVA arm who experienced CVF did not meet the protocol-defined criteria for CVF, but was included due to a viral load count ≥200 copies/mL measured at study site using a non-protocol specified assay
CVF was defined as 2 consecutive HIV-1 RNA levels ≥200 copies/mL

Resistance observed in 1% of patients receiving CABENUVA

As a prespecified secondary endpoint, patients who met the CVF criteria (12/1045) were tested for emergent INSTI or NNRTI substitutions conferring resistance through 96 weeks.^{1, 3}

RESISTANCE-ASSOCIATED MUTATIONS IN PATIENTS WHO MET PROTOCOL-DEFINED CVF^1,3

All clinical isolates from patients who failed with resistance (exploratory analysis):
- Maintained phenotypic susceptibility to multiple other ARVs, including dolutegravir, boosted PIs, and/or nearly all NRTIs¹
- 11 of the 12 patients who failed resuppressed on oral highly active retroviral therapy³
  - One patient who failed to achieve re-suppression reported poor adherence to PI-based ARV therapy³

^*Suspected virologic failure time point.³

Patient-Reported Outcomes for Every-2-Month CABENUVA

ATLAS-2M incorporated data from the patient perspective for every-2-month CABENUVA.¹

These data, collected directly from patients, should not be used to infer clinical significance and should not be interpreted as a reflection of the safety or efficacy of a regimen.

9 out of 10 patients preferred every-2-month CABENUVA

In ATLAS-2M, patient preference was a secondary endpoint. At Week 48, patients in the ITT-E population responded to a questionnaire assessing their preference for HIV treatment.¹

Patients were asked, "For the past year, you have been receiving long-acting injectable medication for the treatment of HIV. Today, we would like you to compare your experience using every-2-month CABENUVA with your experience taking the oral medications cabotegravir and rilpivirine you received during the oral lead-in phase. Based on your experience, which HIV treatment do you prefer?"

ATLAS-2M: PATIENT-REPORTED PREFERENCE¹

References:

Data on file, ViiV Healthcare.
Overton ET, Richmond G, Rizzardini G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomized, multicentre, open-label, phase 3b, non-inferiority study. Lancet. 2020;396(10267):1994-2005. doi:10.1016/S0140-6736(20)32666-0
Jaeger H, Overton ET, Richmond G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 96-week results: a randomized, multicentre, open-label, phase 3b, non-inferiority study. Lancet HIV. 2021;8(11):e679-e689. doi: 10.1016/S2352-3018(21)00185-5

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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

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions:

Hypersensitivity reactions, including cases of drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during postmarketing 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

Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with CABENUVA

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

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 patients 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 or attempt) have been reported with CABENUVA or the individual products

Promptly evaluate patients with depressive symptoms

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

ADVERSE REACTIONS

The most common adverse reactions in adults (incidence ≥2%, all grades) treated with CABENUVA were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash

The safety of CABENUVA in adolescents is expected to be similar to adults

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

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: The CDC recommends that HIV‑1−infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection. Breastfeeding is also not recommended due to the potential for developing viral resistance in HIV-positive infants, adverse reactions in a breastfed infant, and detectable cabotegravir and rilpivirine concentrations in systemic circulation for up to 12 months or longer after discontinuing injections of CABENUVA

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.

Please see full Prescribing Information for CABENUVA.

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To report SUSPECTED ADVERSE REACTIONS, contact ViiV Healthcare at
1-877-844-8872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information for CABENUVA.

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CBRWCNT210044 December 2021

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