ATLAS

&

FLAIR

EFFICACY

Once-monthly CABENUVA vs daily oral therapy1-3

  • ATLAS and FLAIR were phase 3, international, open-label, randomized clinical trials1
  • They were 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
  • The primary endpoint for both studies was the proportion of patients with HIV-1 RNA ≥50 copies/mL at Week 482,3

Selected exclusion criteria2,3:

  • 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

    ATLAS2
    FLAIR3

    *≥18 years of age.2

    †HIV-1 RNA <50 copies/mL.2

    ‡Third agent included INSTI, NNRTI, or PI.2

    §Oral lead-in regimen consisted of 30-mg cabotegravir and 25-mg rilpivirine once daily for at least 1 month.2,3

    ||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.2,3

    Defined as ≤10 days of prior therapy with any ARV following a diagnosis of HIV-1 infection. Screening HIV-1 RNA ≥1000 copies/mL.3

    #Or DTG + 2 NRTIs if HLA-B*5701-positive.3

    **Patients required to have HIV-1 RNA <50 copies/mL by 4 weeks prior to randomization.3

  • ATLAS & FLAIR Baseline Characteristics<sup>1-3</sup>

      ATLAS (N=616)   FLAIR (N=566)
    CABENUVA
    (n=308)    		 2 NRTIs + third agent*
    (n=308)    		   CABENUVA
    (n=283)    		 ABC/DTG/3TC†
    (n=283)
    Median age, years (range) 40 (21 to 74) 43 (18 to 82)   34 (19 to 68) 34 (18 to 68)
    Sex at birth, Female 32% 34%   22%‖ 23%
    Race, White 69% 67%   76% 71%
    Race, Black/African American 20% 25%   17% 20%
    Race, Other 10% 8%   7% 9%
    Baseline HIV-1 RNA Patients with ≥100,000 copies/mL‡ N/A N/A   20%# 20%#
    Median baseline CD4+ T-cell count cells/mm3 (IQR) 654 (497–816) 653 (488–844)   624 (473–839) 625 (472–799)
    Baseline CD4+ T-cell count
    <350 cells/mm3    		 7% 9%   7% 10%
    Median duration of prior ARV therapy, years (range) 4 (1–19) 4 (1–21)   20 Weeks** 20 Weeks**
    Baseline third agent in ARV therapy
    NNRTI
    INSTI
    PI    		 50%
    33%
    17%    		 50%
    33%
    18%    		   0
    100
    0    		 0
    100
    0
    Hepatitis C co-infection§ 7% 10%   7% 3%
      ATLAS (N=616)
    CABENUVA
    (n=308)    		 2 NRTIs + third agent*
    (n=308)
    Median age, years (range) 40 (21 to 74) 43 (18 to 82)
    Sex at birth, Female 32% 34%
    Race, White 69% 67%
    Race, Black/African American 20% 25%
    Race, Other 10% 8%
    Baseline HIV-1 RNA Patients with ≥100,000 copies/mL‡ N/A N/A
    Median baseline CD4+ T-cell count cells/mm3 (IQR) 654 (497–816) 653 (488–844)
    Baseline CD4+ T-cell count
    <350 cells/mm3    		 7% 9%
    Median duration of prior ARV therapy, years (range) 4 (1–19) 4 (1–21)
    Baseline third agent in ARV
    therapy
    NNRTI
    INSTI
    PI    		 50%
    33%
    17%    		 50%
    33%
    18%
    Hepatitis C co-infection§ 7% 10%
      FLAIR (N=566)
    CABENUVA
    (n=283)    		 ABC/DTG/3TC†
    (n=283)
    Median age, years (range) 34 (19 to 68) 34 (18 to 68)
    Sex at birth, Female 22%‖ 23%
    Race, White 76% 71%
    Race, Black/African American 17% 20%
    Race, Other 7% 9%
    Baseline HIV-1 RNA Patients with ≥100,000 copies/mL‡ 20%# 20%#
    Median baseline CD4+ T-cell count cells/mm3 (IQR) 624 (473–839) 625 (472–799)
    Baseline CD4+ T-cell count
    <350 cells/mm3    		 7% 10%
    Median duration of prior ARV therapy, years (range) 20 Weeks** 20 Weeks**
    Baseline third agent in ARV
    therapy
    NNRTI
    INSTI
    PI    		 0
    100
    0    		 0
    100
    0
    Hepatitis C co-infection§ 7% 3%

    *INSTI, NNRTI, or PI.

    †Or DTG + 2 NRTIs if HLA-B*5701-positive.

    ‡Baseline HIV-1 RNA measured prior to induction with ABC/DTG/3TC.

    §Patients with hepatitis B co-infection were excluded from the trials.

    ||Two patients in FLAIR who were male at birth identified as transgender at enrollment.

    Baseline race information was missing for 2 patients in the oral comparator arm in FLAIR.

    #For FLAIR, baseline was considered as Day 1.

    **Patients in FLAIR had no previous ARV exposure prior to induction with ABC/DTG/3TC.

  • ATLAS & FLAIR: Efficacy  

    CABENUVA was as effective as continuing a daily oral regimen1-3*

    Pooled analysis: ITT-E FDA snapshot virologic outcomes at Week 481
    • No virologic data at Week 48: 5% (30/591) CABENUVA; 4% (23/591) oral comparator2,3

    *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

  • ATLAS & FLAIR: CVF

    Pooled analysis: CVF through Week 481
    • CVF is defined as 2 consecutive plasma HIV-1 RNA ≥200 copies/mL1

    *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.1

    †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).2,3

    Resistance data in clinical trials reinforced in the real world

    Explore CVF

  • FLAIR 96 Weeks: Efficacy data

    CABENUVA was as effective as continuing a daily oral regimen4*

    CABENUVA found to be noninferior to ABC/DTG/3TC*
    (upper bound of the 95% CI for the treatment difference was <6%), ITT-E FDA Snapshot
    • No virologic data at Week 96: 10% (29/283) CABENUVA; 7% (21/283) ABC/DTG/3TC*

    *Or DTG plus 2 NRTIs if HLA-B*5701-positive.3

  • FLAIR 96 Weeks: CVF data

    FLAIR: CVF between Week 48 and Week 964
    • A total of 3 CVFs‡ were reported through Week 96 in the CABENUVA arm vs 4 CVFs in the ABC/DTG/3TC* arm
    • Three patients in the CABENUVA arm and 0 patients in the ABC/DTG/3TC arm developed treatment-emergent genotypic resistance through Week 96

    *Or DTG plus 2 NRTIs if HLA-B*5701-positive.3,4

    †CVF occurred at Week 64 with no resistance mutations.4

    ‡One additional CVF was a patient who did not receive an injection dose of CABENUVA.4

ATLAS

&

FLAIR

SAFETY

Majority of adverse reactions were Grades 1-21-3,5

Pooled analysis: Adverse reactions* (all grades†) reported in ≥2% of patients through Week 485

  • 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 Grades 4-5 ISRs
  • 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%)
  CABENUVA
(n=591)		   ORAL COMPARATOR
(n=591)
Adverse reactions All Grades Grades 1–2 Grades 3–4   All Grades Grades 1–2 Grades 3–4
ISRs 83% 79% 4%   N/A N/A N/A
Pyrexia‡ 8% 7% 1%   0% 0% 0%
Fatigue§ 5% 5% 0%   <1% <1% 0%
Headache 4% 4% <1%   <1% <1% 0%
Musculoskeletal pain‖ 3% 3% 0%   <1% <1% 0%
Nausea 3% 2% <1%   1% 1% 0%
Sleep disorders 2% 2% <1%   <1% <1% 0%
Dizziness 2% 2% 0%   <1% <1% 0%
Rash# 2% 2% 0%   0% 0% 0%
Discontinued due to AEs 4%   2%
  CABENUVA
(n=591)
Adverse reactions All Grades Grades 1–2 Grades 3–4
ISRs 83% 79% 4%
Pyrexia‡ 8% 7% 1%
Fatigue§ 5% 5% 0%
Headache 4% 4% <1%
Musculoskeletal pain‖ 3% 3% 0%
Nausea 3% 2% <1%
Sleep disorders 2% 2% <1%
Dizziness 2% 2% 0%
Rash# 2% 2% 0%
Discontinued due to AEs 4%
  ORAL COMPARATOR
(n=591)
Adverse reactions All Grades Grades 1–2 Grades 3–4
ISRs N/A N/A N/A
Pyrexia‡ 0% 0% 0%
Fatigue§ <1% <1% 0%
Headache <1% <1% 0%
Musculoskeletal pain‖ <1% <1% 0%
Nausea 1% 1% 0%
Sleep disorders <1% <1% 0%
Dizziness <1% <1% 0%
Rash# 0% 0% 0%
Discontinued due to AEs 2%

*Adverse reactions defined as “treatment-related” as assessed by the investigator.

†Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=potentially life-threatening; Grade 5=death.6

‡Pyrexia: includes pyrexia, feeling hot, chills, influenza-like illness, body temperature increased.

§Fatigue: includes fatigue, malaise, asthenia.

||Musculoskeletal pain: includes musculoskeletal pain, musculoskeletal discomfort, back pain, myalgia, pain in extremity.

Sleep disorders: includes insomnia, poor quality sleep, somnolence.

#Rash: includes erythema, pruritus, pruritus generalized, purpura, rash-erythematous, generalized, macular.

  • Pooled results through Week 48: Patient-reported local ISRs decreased over time<sup>1</sup>

    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.  

    Pooled analysis (secondary endpoint): Incidence of ISRs reported by visit (all grades)1

  • Pooled results through Week 48: Most common local ISR was pain<sup>1</sup>

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

    Pooled analysis: Patients  (>1%) reporting ISRs through Week 48
      CABENUVA
    (N=591)
    Localized pain 458 (77%)*
    Nodule 81 (14%)
    Induration 68 (12%)
    Swelling 46 (8%)
    Erythema 26 (4%)
    Pruritus 23 (4%)
    Bruising 17 (3%)
    Warmth 14 (2%)
    Hematoma 11 (2%)

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

    Pooled analysis: ISR events by injections given through Week 48
      CABENUVA
    (N=591)
    Localized pain 3087 (21%)
    Nodule 140 (1%)
    Induration 136 (<1%)
    Swelling 86 (<1%)
    Erythema 60 (<1%)
    Pruritus 37 (<1%)
    Bruising 24 (<1%)
    Warmth 47 (<1%)
    Hematoma 12 (<1%)
    • Abscess and cellulitis at the injection site were each reported in <1% of patients

    *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.

  • FLAIR 96 Weeks: Safety Data

    Adverse reactions were similar at Week 48 and Week 964

    Safety overview
      Cumulative AEs through Week 48   Cumulative AEs through Week 96   New patients with AEs between Week 48 and Week 96
    CABENUVA
    (n=283)    		 ABC/DTG/3TC*
    (n=283)    		   CABENUVA
    (n=283)    		 ABC/DTG/3TC*
    (n=283)    		   CABENUVA
    (n=283)    		 ABC/DTG/3TC*
    (n=283)
    Drug-related AEs (excluding ISRs) 28% 10%†   34% 12%   n=16§ n=6ll
    Drug-related Grades 3–4‡ AEs 5% 0%   6% 0%   n=2 n=0
    Drug-related SAE <1% 0%   <1% 0%   n=0 n=0
      Cumulative AEs through Week 48
    CABENUVA
    (n=283)    		 ABC/DTG/3TC*
    (n=283)
    Drug-related AEs (excluding ISRs) 28% 10%†
    Drug-related Grades 3–4‡ AEs 5% 0%
    Drug-related SAE <1% 0%
      Cumulative AEs through Week 96
    CABENUVA
    (n=283)    		 ABC/DTG/3TC*
    (n=283)
    Drug-related AEs (excluding ISRs) 34% 12%
    Drug-related Grades 3–4‡ AEs 6% 0%
    Drug-related SAE <1% 0%
      New patients with AEs between Week 48 and Week 96
    CABENUVA
    (n=283)    		 ABC/DTG/3TC*
    (n=283)
    Drug-related AEs (excluding ISRs) n=16§ n=6ll
    Drug-related Grades 3–4‡ AEs n=2 n=0
    Drug-related SAE n=0 n=0

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

    †Includes 1 subject at Week-48 data analysis who is not present at Week-96 data analysis.4

    ‡Grade 3=severe; Grade 4=potentially life-threatening.6

    §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.4

    ||1 diarrhea/abdominal pain/nasopharyngitis/eye pain, 1 insomnia, 1 abnormal dreams, 1 poor-quality sleep, 1 nausea, 1 hypercholesterolemia/vitamin D decreased.4

    No new safety signals identified through Week 964

    88% of patients experienced at least one ISR through Week 964
    Adverse reactions* (all grades, excluding local ISRs) reported in ≥3% of patients in either arm through Week 964
      CABENUVA
    (n=283)    		 ABC/DTG/3TC†
    (n=283)
    Pyrexia 6% 0%
    Headache 5% 1%
    Asthenia 3% 0%
    Body temperature increased 3% 0%
    Discontinued due to AEs 5%‡ 1%
    • 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])
    • Between Week 48 and Week 96, 1 patient withdrew due to an ISR
    • 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"

    *Adverse reactions defined as “treatment-related” as assessed by the investigator. 

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

    ‡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.

    FLAIR 96 Weeks: ISRs5

    1% of patients discontinued due to ISRs through Week 965

    In FLAIR, through Week 96: 

    • The majority (3082/3100, 99%) of ISRs were Grade 1-2
    • Most (89%) ISR events resolved within ≤7 days (median [IQR] duration of 3 [2 to 4] days)
    • Patient-reported local ISRs decreased from baseline to Week 96
      • 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 96

    Patients (≥5%) reporting ISRs through Week 96
      CABENUVA
    (n=283)
    Localized pain 235 (85%)
    Nodule 58 (21%)
    Induration 44 (16%)
    Swelling 30 (11%)
    Pruritus 26 (9%)
    Erythema 17 (6%)

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

    ISR events (most frequent) by injections given
    through Week 96
      CABENUVA
    (n=283)
    Localized pain 2613 (21%)
    Nodule 132 (1%)
    Induration 119 (<1%)
    Swelling 45 (<1%)
    Pruritus 56 (<1%)
    Warmth 59 (<1%)

You may have virologically suppressed patients like Gabriel who are ready to switch to a long-acting regimen

At time of switch, recently suppressed on shorter-acting ART and wanted a treatment that fit into a routine he envisioned

See Gabriel’s story

3TC=lamivudine; ABC=abacavir; AE=adverse event; ART=antiretroviral therapy; ARV=antiretroviral; CI=confidence interval; CVF=confirmed virologic failure; DTG=dolutegravir; FDA=Food and Drug Administration; INSTI=integrase strand-transfer inhibitor; ITT-E=intent-to-treat exposed; ISR=injection site reaction; IQR=interquartile range; NNRTI=non-nucleoside reverse transcriptase inhibitor; NRTI=nucleoside reverse transcriptase inhibitor; PI=protease inhibitor; SAE=serious adverse event.

References:

  1. 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.
  2. 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
  3. 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
  4. 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.
  5. Data on file. ViiV Healthcare group of companies. Durham, NC.
  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-CBRWCNT250025