ATLAS-2M efficacy and safety: Every-2-month vs once-monthly CABENUVA

ATLAS-2M: Efficacy

Study design

Every-2-month vs once-monthly CABENUVA

ATLAS-2M study design graphic

Selected exclusion criteria1:

  • Previous virologic failure
  • Any known INSTI or NNRTI resistance (excluding K103N)
  • HBV infection at screening
  • Moderate to severe hepatic impairment
  • Women who were pregnant or breastfeeding, or planned to become pregnant or breastfeed
  1. Acceptable ARV regimens (either initial or second ARV regimen) included 2 NRTIs plus an INSTI, NNRTI, or boosted PI (or ATV unboosted).2
  2. Patients transitioning from the ATLAS trial who were on oral antiretroviral therapy must have been on their current oral regimen for at least 52 weeks and had plasma HIV-1 RNA <50 copies/mL.2
  3. Newly enrolled patients were virologically suppressed for at least 6 months on 2 NRTIs + third agent, with suppression defined as plasma HIV-1 RNA <50 copies/mL.1
  4. Patients transitioning from ATLAS on once-monthly CABENUVA either completed at least 52 weeks in the comparative phase or switched from an oral regimen after Week 52 in the extension phase and had plasma HIV-1 RNA <50 copies/mL.1
  5. Oral lead-in regimen consisting of 30-mg cabotegravir and 25-mg rilpivirine given once daily for 4 weeks.
  6. Patients transitioning from the ATLAS trial with once-monthly exposure to CABENUVA received their first injections on Day 1.1

ATLAS-2M baseline characteristics

ATLAS-2M included a range of patients1

  • 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
ATLAS-2M study baseline characteristics table
  1. 8 patients who were assigned male at birth identified as female at enrollment.1

ATLAS-2M: It starts with proven efficacy

Every-2-month CABENUVA was proven as effective as once-monthly CABENUVA1,3

ATLAS-2M: ITT-E FDA snapshot virologic outcomes through Week 152

ATLAS-2M primary efficacy endpoint chart
ATLAS-2M secondary efficacy endpoint chart
ATLAS-2M confirmed virologic failure through Week 152 graphic
  1. CVF was defined as 2 consecutive RNA levels ≥200 copies/mL.1
  2. One patient who was included as a CVF did not meet the protocol-defined criteria but was included due to a viral load ≥200 copies/mL measured at study site using a non-protocol–specified assay.1,3

ATLAS-2M: Confirmed virologic failure

CVF with resistance observed in patients receiving CABENUVA in ATLAS-2M2,3

As a prespecified secondary endpoint, patients who met the protocol-defined CVF criteria (14/1045) were tested for emergent INSTI (cabotegravir) or NNRTI (rilpivirine) substitutions conferring resistance by 152 weeks3

ATLAS-2M confirmed virologic failure table

All clinical isolates from patients who failed with resistance (exploratory analysis)3,4

  • Maintained phenotypic susceptibility to multiple ARVs including dolutegravir, bictegravir, boosted PIs, and/or nearly all NNRTIs
  • 13 of the 14 patients who failed re-suppressed on oral, highly active retroviral therapy
  • 1 patient who failed to achieve re-suppression reported poor adherence to PI-based ARV therapy
  1. One patient who was included as CVF did not meet the protocol-defined criteria but was included due to a viral load ≥200 copies/mL measured at study site using a non-protocol specified assay.3,4
  2. Suspected virologic failure time point.4

ATLAS-2M: Safety

ATLAS-2M drug-related adverse events through Week 152 table ATLAS-2M drug-related adverse events through Week 152 table

Drug-related adverse events through Week 1522,3

ATLAS-2M: The majority of adverse reactions were Grade 1-2 injection site reactions (ISRs) and were the most common side effect associated with CABENUVA in both arms, the majority of which were mild to moderate and short in duration.2

  1. Adverse reactions defined as “treatment-related” as assessed by the investigator.
  2. Pyrexia: includes pyrexia, feeling hot, chills, influenza-like illness, body temperature increased.
  3. Fatigue: includes fatigue, malaise, asthenia.
  4. Musculoskeletal pain: includes musculoskeletal pain, musculoskeletal discomfort, back pain, myalgia, pain in extremity.
  5. Rash: includes erythema, pruritus, pruritus generalized, purpura, rash, rash-erythematous, generalized, macular.
  6. Sleep disorders: includes insomnia, poor quality sleep, somnolence.

ATLAS-2M: ISRs through Week 152

  • ISRs were consistent across ATLAS-2M and SOLAR1

  • Rate of ISRs at each visit decreased over the first 48 weeks and remained consistent thereafter2

    • Self-reported ISRs could potentially underestimate the true rate of ISRs over time; ISRs may still be present but not reported during the study
  • Discontinuations due to injection-related reasons: every-2-month=2%, once-monthly=3%
  • Median duration was 3 days (IQR 2-5 days) in both arms1,2

When it’s time to start CABENUVA, ViiV can help

Discover access resources

AE=adverse event; ARV=antiretroviral; ATV=atazanavir; BMI=body mass index; CI=confidence interval; CVF=confirmed virologic failure; FDA=Food and Drug Administration; HBV=hepatitis B virus; INSTI=integrase strand transfer inhibitor; IQR=interquartile range; ITT-E=intent-to-treat exposed; NNRTI=non-nucleoside reverse transcriptase inhibitor; NRTI=nucleoside reverse transcriptase inhibitor; PI=protease inhibitor; W=Week.

References:

  1. 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 randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet. 2020;396(10267):1994-2005. doi:10.1016/S0140-6736(20)32666-0
  2. Data on file. ViiV Healthcare group of companies. Durham, NC.
  3. Overton ET, Richmond G, Rizzardini G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with human immunodeficiency virus 1 type 1 infection: 152-week results from ATLAS-2M, a randomized, open-label, phase 3b, noninferiority study. Clin Infect Dis. 2023;76(9):1646-1654.
  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 randomised, 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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