ATLAS and FLAIR efficacy and safety: Once-monthly CABENUVA vs daily oral therapy

ATLAS and FLAIR: Efficacy

Once-monthly CABENUVA vs daily oral therapy1,2

ATLAS and FLAIR were clinical trials designed to evaluate the efficacy and safety of long-acting CABENUVA in adult (≥18 years) patients with HIV-1 who were virologically suppressed at time of randomization.3 The primary endpoint for both studies was the proportion of patients with HIV-1 RNA ≥50 copies/mL at Week 48.1,2

Selected exclusion criteria1,2:

  • Patients with hepatitis B virus infection at screening
  • Patients with moderate to severe hepatic impairment
  • Women who are pregnant, breastfeeding, or plan to become pregnant or breastfeed during the study

ATLAS & FLAIR study designs

ATLAS & FLAIR: Phase 3, international, open-label, randomized trials

ATLAS Trial Design1

ATLAS trial design graphic

FLAIR Trial Design2

FLAIR trial design graphic
  1. ≥18 years of age.1,2
  2. HIV-1 RNA <50 copies/mL.1
  3. Third agent included INSTI, NNRTI, or PI.1 
  4. Oral lead-in regimen consisted of 30-mg cabotegravir and 25-mg rilpivirine once daily for at least 1 month.1,2
  5. On the last day of the oral lead-in, patients received initiation injections of cabotegravir and rilpivirine followed by continuation injections 1 month later and then monthly thereafter.1,2
  6. Defined as ≤10 days of prior therapy with any ARV following a diagnosis of HIV-1 infection. Screening HIV-1 RNA ≥1000 copies/mL.2
  7. Or DTG + 2 NRTIs if HLA-B*5701-positive.2

**Patients required to have HIV-1 RNA <50 copies/mL by 4 weeks prior to randomization.2

ATLAS & FLAIR baseline characteristics

ATLAS and FLAIR were designed to evaluate the efficacy and safety of long-acting CABENUVA in a range of virologically suppressed adult patients with HIV-11,2

Baseline patient characteristics by trial1,2,4:

ATLAS & FLAIR baseline characteristics table
ATLAS FLAIR baseline characteristics chart
  1. INSTI, NNRTI, or PI.1
  2. Or DTG + 2 NRTIs if HLA-B*5701- positive.2
  3. Baseline HIV-1 RNA measured prior to induction with abacavir/dolutegravir/lamivudine.4
  4. Patients with hepatitis B co-infection were excluded from the trials.2,3
  5. Two patients in FLAIR who were male at birth identified as transgender at enrollment.4
  6. Baseline race information was missing for 2 patients in the oral comparator arm in FLAIR.3
  7. For FLAIR, baseline was considered as Day 1.3

**Patients in FLAIR had no previous ARV exposure prior to induction with abacavir/dolutegravir/lamivudine.

ATLAS & FLAIR: It starts with proven efficacy

CABENUVA was proven as effective as continuing a daily oral regimen3*

The efficacy and safety of CABENUVA were evaluated in 2 phase 3 clinical trials (ATLAS and FLAIR). CABENUVA was found to be non-inferior to daily oral comparator (upper bound of 95% CI for the treatment difference was <4%) at Week 48 for the primary endpoint (HIV-1 RNA ≥50 copies/mL).3

Pooled analysis: ITT-E FDA snapshot virologic outcomes at Week 483

ATLAS & FLAIR primary endpoint chart
ATLAS & FLAIR secondary endpoint chart
  • No virologic data at Week 48: 5% (30/591) CABENUVA; 4% (23/591) oral comparator3

*In ATLAS, the oral comparator consisted of 2 NRTIs + a third agent (INSTI, NNRTI, or PI). In FLAIR, the oral comparator consisted of ABC/DTG/3TC (or DTG + 2 NRTIs if HLA-B*5701-positive).3

ATLAS & FLAIR: Confirmed virologic failure (CVF)

CVF from ATLAS and FLAIR

Similar incidence of CVF across both arms3

ATLAS & FLAIR confirmed virologic failure through Week 48 graphic
  • CVF is defined as 2 consecutive plasma HIV-1 RNA ≥200 copies/mL3
  1. One additional patient on oral cabotegravir and rilpivirine, taken during the oral lead-in phase, met CVF criteria (7 CVFs total). No resistance mutations were detected in this patient.3
  2. In ATLAS, the oral comparator consisted of 2 NRTIs + a third agent (INSTI, NNRTI, or PI). In FLAIR, the oral comparator consisted of ABC/DTG/3TC (or DTG + 2 NRTIs if HLA-B*5701-positive).1,2

FLAIR 96 Weeks: Efficacy data

Proven as effective as continuing ABC/DTG/3TC through Week 965

FLAIR: ITT-E FDA snapshot virologic outcomes at Week 965

CABENUVA found to be non-inferior to ABC/DTG/3TC* (upper bound of the 95% CI for the treatment difference was <6%)5

FLAIR efficacy data at Week 96 chart
FLAIR 96 weeks virologic outcomes graphic
  • No virologic data at Week 96: 10% (29/283) CABENUVA; 7% (21/283) ABC/DTG/3TC5*

*Or DTG plus 2 NRTIs if HLA-B*5701-positive.5

FLAIR 96 Weeks: CVF data

FLAIR CVF CABENUVA vs ABC DTG 3TC graphic
  • A total of 3 CVFs‡ were reported through Week 96 in the CABENUVA arm vs 4 CVFs in the ABC/DTG/3TC* arm5
  • Three patients in the CABENUVA arm and 0 patients in the ABC/DTG/3TC arm developed treatment-emergent genotypic resistance through Week 965
  1. Or DTG plus 2 NRTIs if HLA-B*5701-positive.5
  2. CVF occurred at Week 64 with no resistance mutations.5
  3. One additional CVF was a patient who did not receive an injection dose of CABENUVA.5

ATLAS and FLAIR: Safety

Safety of once-monthly CABENUVA

CABENUVA was studied in ATLAS and FLAIR, two robust, phase 3, non-inferiority trials designed to evaluate the efficacy and safety of long-acting CABENUVA in adult (≥18 years) patients with HIV-1 who were virologically suppressed at time of randomization1,2

Majority of adverse reactions were Grades 1-2

Pooled analysis: Adverse reactions* (all grades†) reported in ≥2% of patients through week 48

Injection site reactions (ISRs) were the most common side effect associated with CABENUVA, the majority of which were mild to moderate.

  • 4% of patients experienced Grade 3 ISRs, and no patients experienced Grade 4-5 ISRs³
  • Non-injection site-related adverse reactions leading to discontinuation and occurring in >1 patient were headache, diarrhea, hepatitis A, and acute hepatitis B (all with an incidence <1%)
ATLAS & FLAIR pooled analysis of adverse reactions table
ATLAS FLAIR AEs grade comparison graphic
  1. Adverse reactions defined as “treatment-related” as assessed by the investigator.
  2. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=potentially life-threatening; Grade 5=death.⁴
  3. Pyrexia: includes pyrexia, feeling hot, chills, influenza-like illness, body temperature increased.
  4. Fatigue: includes fatigue, malaise, asthenia.
  5. Musculoskeletal pain: includes musculoskeletal pain, musculoskeletal discomfort, back pain, myalgia, pain in extremity.
  6. Sleep disorders: includes insomnia, poor quality sleep, somnolence.
  7. Rash: includes erythema, pruritus, pruritus generalized, purpura, rash-erythematous, generalized, macular.

Pooled results through Week 48: Patient-reported local ISRs decreased over time3

Pooled analysis (secondary endpoint): Incidence of ISRs reported by visit (all grades)3

Overall, 83% of patients experienced at least one ISR through Week 48.

Self-reported ISRs could potentially underestimate the true rate of ISRs over time. ISRs may still be present but not reported during the course of the study.

ATLAS & FLAIR injection site reactions through Week 48

Pooled results through Week 48: Most common local ISR was pain3

83% of patients experienced at least one ISR through Week 48

Pooled analysis: Patients  (>1%) reporting ISRs through week 48

Patients reporting ISRs through week 48 table

3663 ISRs (25%) were reported after 14,682 injections3

Pooled analysis: ISR events by injections given through week 48

ISR events by injections through week 48 table

*591 patients were used to calculate the 77% reporting localized pain, as opposed to 581 patients used to calculate the 79% listed in the Prescribing Information for CABENUVA.4

  • Abscess and cellulitis at the injection site were each reported in <1% of patients

  • FLAIR 96 Weeks: Safety Data

    Adverse reactions were similar at Week 48 and Week 965

    Safety overview5

    FLAIR adverse reactions at Week 48 and Week 96 table
    1. Or DTG plus 2 NRTIs if HLA-B*5701-positive.
    2. Includes 1 subject at Week-48 data analysis who is not present at Week-96 data analysis.5
    3. Grade 3=severe; Grade 4=potentially life-threatening.6
    4. 2 pyrexia, 2 fatigue, 2 dizziness, 1 headache/nausea, 1 pre-syncope, 1 depressed mood, 1 pyrexia/chills, 1 chronic sinusitis/chronic tonsillitis, 1 back pain and nasopharyngitis, 1 musculoskeletal pain, 1 anxiety, 1 influenza-like illness, 1 asthenia/depressed mood.5
    5. 1 diarrhea/abdominal pain/nasopharyngitis/eye pain, 1 insomnia, 1 abnormal dreams, 1 poor-quality sleep, 1 nausea, 1 hypercholesterolemia/vitamin D decreased.5

    No new safety signals identified through Week 96

    88% of patients experienced at least one ISR through Week 965

    Adverse reactions* (all grades, excluding local ISRs) reported in ≥3% of patients in either arm through Week 965

    FLAIR adverse reactions through Week 96 table
    • The majority (3082/3100, 99%) of ISRs were Grades 1-2 and most (89%) resolved within ≤7 days (median duration of 3 days [interquartile range, 2 to 4])5
    • Between Week 48 and Week 96, 1 patient withdrew due to an ISR5
    • An additional 3 patients receiving CABENUVA withdrew from the study through Week 96; the primary reason for discontinuation given was "withdrew consent due to intolerability of injections"5
    1. Adverse reactions defined as “treatment-related” as assessed by the investigator.2
    2. Or DTG plus 2 NRTIs if HLA-B*5701-positive.2,5
    3. Between Weeks 48 and 96, discontinuations occurred due to: hepatitis A (3); acute hepatitis B (2); depression (2); and 1 each acute hepatitis C, hepatitis C, secondary syphilis, discomfort, diarrhea, vomiting, aminotransferase increased, and adenocarcinoma of the colon; a participant could have more than one reason for withdrawal.5

    FLAIR 96 Weeks: ISRs

    1% of patients discontinued due to ISRs through Week 966

    Between Week 48 and Week 96, 1 additional patient discontinued CABENUVA due to ISRs5*

    In FLAIR, through Week 965:

    • The majority (3082/3100, 99%) of ISRs were Grade 1-25
    • Most (89%) ISR events resolved within ≤7 days (median duration of 3 days [interquartile range, 2 to 4])5

    • Patient-reported local ISRs decreased from baseline to Week 965

      • Self-reported ISRs could potentially underestimate the true rate of ISRs over time. ISRs may still be present but not reported during the course of the study

    88% of patients experienced at least one ISR through Week 965

    Patients (≥5%) reporting ISRs through week 96

    FLAIR patients reporting ISRs through Week 96

    3100 (25%) ISRs were reported after 12,552 injections5

    ISR events (most frequent) by injections given through week 96

    FLAIR ISR events by injections given through Week 96

    *An additional 3 patients receiving CABENUVA withdrew from the study between Week 48 and Week 96; the primary reason for discontinuation given was “withdrew consent due to intolerability of injections.”5

You may have patients who could benefit from a long-acting regimen

Patient Ambassador Miranda Patient Ambassador Miranda

Miranda—Patient Ambassador

Unfortunately, sometimes having a bottle in your medicine cabinet, you know, it just gives you away.

See Miranda's story

3TC=lamivudine; ABC=abacavir; AE=adverse event; ARV=antiretroviral; CI=confidence interval; DTG=dolutegravir; FDA=Food and Drug Administration; INSTI=integrase strand transfer inhibitor; IQR=interquartile range; ITT-E=intent-to-treat exposed; LA=long acting; NA=not applicable; NNRTI=non-nucleoside reverse transcriptase inhibitor; NRTI=nucleoside reverse transcriptase inhibitor; PI=protease inhibitor; SAE=serious adverse event; W=Week.

References:

  1. Swindells S, Andrade-Villanueva J-F, Richmond G, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med. 2020;382(12):1112-1123. doi:10.1056/NEJMoa1904398
  2. Orkin C, Arasteh K, Górgolas Hernández-Mora M, et al. Long-acting cabotegravir and rilpivirine after oral induction for HIV-1 infection. N Engl J Med. 2020;382(12):1124-1135. doi:10.1056/NEJMoa1909412
  3. Rizzardini G, Overton ET, Orkin C, et al. Long-acting injectable cabotegravir + rilpivirine for HIV maintenance therapy: week 48 pooled analysis of phase 3 ATLAS and FLAIR trials. J Acquir Immune Defic Syndr. 2020;85(4):498-506.
  4. Data on file. ViiV Healthcare group of companies. Durham, NC.
  5. Orkin C, Oka S, Philibert P, et al. Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study. Lancet HIV. 2021;8:e185-e196.
  6. US Department of Health and Human Services. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Division of AIDS. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events. Corrected Version 2.1; July 2017.

PMUS-CBRWCNT240093