For virologically suppressed adults 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.1-4

The primary endpoint for the study was the proportion of patients with HIV-1 RNA ≥50 copies/mL at Week 48.1 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 Criteria4:

  • No 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* study1,3,4

ATLAS-2M TRIAL DESIGN1,3,4

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

trial design q2m
atlas 2m

*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 48.3 Acceptable ARV regimens (either initial or second ARV regimen) included 2 NRTIs plus an INSTI, NNRTI, or boosted PI (or ATV unboosted).4 Patients were suppressed for ≥6 months, with suppression defined as HIV-1 RNA <50 copies/mL.4 §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.4 ||Oral lead-in regimen consisted of 30-mg cabotegravir and 25-mg rilpivirine once daily given for 1 month (at least 28 days).1 Patients transitioning from the ATLAS trial with exposure to once-monthly CABENUVA received their first injections on Day 1.3 #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.1

 

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 CHARACTERISTICS3

FLAIR TRIAL DESIGN1-3
baseline chart
  • 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 3

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

IQR=interquartile range.

**8 patients who were assigned male at birth identified as female at enrollment.3

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 96.1,3,4

ATLAS-2M: ITT-E FDA SNAPSHOT VIROLOGIC OUTCOMES THROUGH WEEK 961,3,4

Atlas 2M ITT Chart
CABENUVA efficacy data
  • No virologic data at Week 48: 4% (21/522) in every-2-month CABENUVA; 6% (29/523) in once-monthly CABENUVA3
  • No virologic data at Week 96: 7% (36/522) in every-2-month CABENUVA; 9% (45/523) in once-monthly CABENUVA4

*Primary endpoint: HIV-1 RNA ≥50 copies/mL at Week 48.1 Secondary endpoints: HIV-1 RNA <50 copies/mL at Week 48 and at Week 96, and HIV-1 RNA ≥50 copies/mL at Week 96.3,4

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.4

ATLAS-2M: CONFIRMED VIROLOGIC FAILURE THROUGH WEEK 964

confirmed virologic
confirmed virologic
  • 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/mL1

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.2,4

RESISTANCE-ASSOCIATED MUTATIONS IN PATIENTS WHO MET PROTOCOL-DEFINED CVF1,2,4

resistance mutations
  • 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 NRTIs2
    • 11 of the 12 patients who failed resuppressed on oral highly active retroviral therapy4
      • One patient who failed to achieve re-suppression reported poor adherence to PI-based ARV therapy4


*Suspected virologic failure time point.4

Patient-Reported Outcomes for Every-2-Month CABENUVA

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

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.2

  • 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 PREFERENCE2

Patient Reported Chart
no prior
prior
Patient Reported Chart

References:

  1. CABENUVA [package insert]. Research Triangle Park, NC: ViiV Healthcare; 2021.
  2. Data on file, ViiV Healthcare.
  3. 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
  4. 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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