ATLAS & FLAIR: 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 AEs grade comparison graphic
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 incidence of ISRs reported graphic

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

ATLAS FLAIR patients ISRs graphic

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

Pooled analysis: ISR events by injections given through week 48

ATLAS FLAIR Week 48 ISRs by injections

*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.5

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

Other ISRs

Other injection-associated adverse reactions included an increased incidence of pyrexia (8%)†; reports of musculoskeletal pain (3%) and less frequently, sciatica; and vasovagal or pre-syncopal reactions (<1%).

†No cases were serious or led to withdrawal, and the occurrences of pyrexia may represent a response to administration of CABENUVA via intramuscular injection.

  • FLAIR 96 Weeks: Safety Data

    Adverse reactions were similar at Week 48 and Week 966

    Safety overview6

    FLAIR 96 Weeks Safety graphic
    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.6
    3. Grade 3=severe; Grade 4=potentially life-threatening.4
    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.6
    5. 1 diarrhea/abdominal pain/nasopharyngitis/eye pain, 1 insomnia, 1 abnormal dreams, 1 poor-quality sleep, 1 nausea, 1 hypercholesterolemia/vitamin D decreased.6

    No new safety signals identified through Week 96

    88% of patients experienced at least one ISR through Week 966

    Adverse reactions* (all grades, excluding local ISRs) reported in ≥3% of patients in either arm through Week 966 

    ATLAS FLAIR Week 96 AEs reported
    • 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])6
    • Between Week 48 and Week 96, 1 patient withdrew due to an ISR6
    • 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"6
    1. Adverse reactions defined as “treatment-related” as assessed by the investigator.2
    2. Or DTG plus 2 NRTIs if HLA-B*5701-positive.2,6
    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.6

    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 ISRs6*

    In FLAIR, through Week 966:

    • The majority (3082/3100, 99%) of ISRs were Grade 1-26
    • Most (89%) ISR events resolved within ≤7 days (median duration of 3 days [interquartile range, 2 to 4])6

    • Patient-reported local ISRs decreased from baseline to Week 966

      • 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 966

    Patients (≥5%) reporting ISRs through week 96

    FLAIR Week 96 patients ISRs graphic

    3100 (25%) ISRs were reported after 12,552 injections6

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

    FLAIR Week 96 ISR events by injections

    *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.”6

See safety data for ATLAS-2M

Alternate Site of Care (ASOC):

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You provide patient care, and the ASOC can manage everything from benefits verification to administering injections to reimbursement.

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3TC=lamivudine; ABC=abacavir; AE=adverse event; DTG=dolutegravir; NA=not applicable; NRTI=nucleoside reverse transcriptase inhibitor; SAE=serious adverse event.

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. 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.
  5. Data on file. ViiV Healthcare group of companies. Durham, NC.
  6. 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.

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