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 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
*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
- 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.
**8 patients who were assigned male at birth identified as female at enrollment.3
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
- 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.
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
- 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
- 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
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
- CABENUVA [package insert]. Research Triangle Park, NC: ViiV Healthcare; 2021.
- 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