SOLAR

EFFICACY

Every-2-month CABENUVA was noninferior to daily oral BIKTARVY1

SOLAR, a phase 3b clinical trial, is the first head-to-head switch study comparing every-2-month CABENUVA with daily oral BIKTARVY1,2

  • SOLAR Study Design

    A large phase 3b, open-label, noninferiority study of virologically suppressed* adults (≥18 years) with HIV-1
    Primary endpoint (mITT-E population)

    Proportion of patients with HIV-1 RNA ≥50 copies/mL in the Month 12 analysis

    Secondary efficacy endpoint

    Proportion of patients with HIV-1 RNA <50 copies/mL in the Month 12 analysis

    Exclusion criteria
    • History of virologic failure
    • Known or suspected presence of resistance mutations to the individual components of BIKTARVY or CABENUVA
    • HBV infection at screening
    • Moderate to severe hepatic impairment
    • Women who were pregnant or breastfeeding or planned to become pregnant or breastfeed
    • Efficacy analyses, baseline questionnaire, and preference calculation were based on the mITT-E (N=670) population. After consultation with a blinded external expert, 11 participants at a single study site were excluded from the ITT-E population due to critical findings related to significant and persistent noncompliance to protocol requirements
    • Safety analyses were based on ITT-E (N=681) population

    *Suppression defined as plasma HIV-1 RNA <50 copies/mL. A single prior INSTI-based regimen was allowed for reasons other than treatment failure.

    On last day of the OLI period or oral ART, patients received 2 sets of initiation CABENUVA injections 1 month apart followed by every-2-month injections thereafter.

    ‡ Month 12 (OLI and BIKTARVY) and Month 11 (SWI).

  • SOLAR Baseline Characteristics

    Baseline characteristics (mITT-E population), used for efficacy and patient outcomes1,2
    Baseline Characteristics EVERY-2-MONTH CABENUVA
    (N=447)
    ONCE-DAILY BIKTARVY
    (N=223)
    Median age, years
    Range
    ≥50, %
    37
    18-74
    19
    37
    18-66
    19
    Sex assigned at birth, %
    Female
    Male

    17
    83

    18
    82
    Race, %
    White
    Black/African American
    Other

    69
    21
    10

    70
    22
    8
    Hispanic or Latinx ethnicity, % 21 17
    Median (IQR) BMI, kg/m2
    ≥30
    26 (23–29)
    21%
    25 (23–29)
    23%
    Median (IQR) CD4+ count, cells/mm3
    <350, %
    649 (477–850)
    12
    640 (459–846)
    13
    Median duration of prior BIKTARVY, years 1.8 1.7
    Baseline Characteristics EVERY-2-MONTH CABENUVA
    (N=447)
    ONCE-DAILY BIKTARVY
    (N=223)
    Median age,
    years
    Range
    ≥50, %
    37

    18-74
    19
    37

    18-66
    19
    Sex assigned
    at birth, %
    Female
    Male


    17
    83


    18
    82
    Race, %
    White
    Black/African
    American
    Other

    69
    21

    10

    70
    22

    8
    Hispanic or Latinx ethnicity, % 21 17
    Median (IQR)
    BMI, kg/m2
    ≥30
    26 (23–29)

    21%
    25 (23–29)

    23%
    Median (IQR)
    CD4+ count,
    cells/mm3
    <350, %
    649 (477–850)


    12
    640 (459–846)


    13
    Median duration of prior BIKTARVY, years 1.8 1.7

    61% (n=274) of patients in the CABENUVA arm started with injections without OLI and 39% (n=173) started with OLI.

  • SOLAR Endpoints

    In SOLAR, the primary endpoint was met (mITT-E; HIV-1 RNA ≥50 copies/mL):
    Every-2-month CABENUVA was noninferior* to BIKTARVY at Month 12 analysis (1% [5/447] vs <1% [1/223], respectively, adjusted difference = 0.7% [95% CI -0.7 to 2.0]).1

    Secondary Endpoint: Plasma HIV-1 RNA <50 copies/mL at Month 12 analysis1†

    *Noninferiority shown if the upper bound of the 95% CI for the treatment difference was <4%.

    Noninferiority shown if the lower bound of the 95% CI for the treatment difference was >-12%.

  • BMI Subset Efficacy

    As effective in patients with higher BMI at 12 months (subset analysis)2,3

    HIV-1 RNA ≥50 copies/mL in participants with BMI ≥30 kg/m2: 1% (1/93) of participants treated with CABENUVA vs 0/52 treated with BIKTARVY (difference=1.1, 95% CI, -6.5, 6.1)
    Plasma HIV-1 RNA <50 copies/mL results with CABENUVA

    Longer needle lengths may be required for patients with higher BMI.

  • SOLAR Confirmed Virologic Failure

    • Key differences in ATLAS-2M: all patients had previously received an NNRTI-, PI-, or INSTI-based regimen. Through Week 152, there were 12 (2%) CVFs in the every-2-month arm and 2 (<1%) in the once-monthly arm4
    • Of the two CVFs on CABENUVA, both patients had RPV and INSTI RAMs observed1

    Patients who met CVF re-suppressed on alternative, highly suppressive antiretroviral therapies.1

    *An additional patient on CABENUVA in the ITT-E population met CVF at Month 3 with RPV RAMs.

SOLAR

SAFETY

  • Drug-related adverse events through Month 12<sup>1,2</sup>

    Most common adverse events ≥1%1,2

    • Most drug-related AEs were Grade 1 or 2 in CABENUVA patients; all were Grade 1 or 2 in BIKTARVY patients
    • 2% of CABENUVA patients (event level) discontinued treatment due to injection-related reasons, and 2% discontinued due to non-ISR, drug-related AEs
    Drug-related AEs* Occurring in ≥1% of Patients in Either Group EVERY-2-MONTH CABENUVA
    (n=454)
    DAILY BIKTARVY
    (n=227)
    ISRs 70% N/A
    Pyrexia 4% 0%
    Fatigue 3% 0%
    Diarrhea 2% 0%
    Headache 2% 0%
    Musculoskeletal pain§ 2% 0%
    Sleep disorders|| 1% 0%
    Nausea 1% 0%
    Dizziness 1% 0%
    Discontinuation rate due to drug-related AEs 4% 0%

    *Defined as “treatment-related” as assessed by the investigator. Only maximum-graded report per adverse reaction contributes to table.

    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.

  • Injection site reactions<sup>1,2</sup>

    • The median (IQR) duration of ISRs was 3 (2-5) days
    • 2% of CABENUVA patients (event level) discontinued treatment due to injection-related reasons
    ISRs ≥5% of patients EVERY-2-MONTH CABENUVA
    (n=454)
    Total ISRs 70%
    Pain 62%
    Nodule 9%
    Swelling 9%
    Discomfort 9%
    Induration 7%
  • Patient-reported ISRs decreased over time<sup>1,2</sup>*

    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

    SOLAR: Incidence of reported ISRs (all grades) by visit

    *Participants’ injection schedule during the maintenance phase: oral lead-in—Month 1, 2, 4, 6, 8, 10, 12; direct to injections—Day 1, Month 1, 3, 5, 7, 9, 11. Data for the 2 arms have been combined.

CABENUVA real-world studies reinforce SOLAR

AE=adverse event; BMI=body mass index; CI=confidence interval; CVF=confirmed virologic failure; HBV=hepatitis B virus; INSTI=integrase strand-transfer inhibitor; IQR=interquartile range; ISR=injection site reaction; ITT-E=intent-to-treat exposed; M=month; mITT-E=modified intent-to-treat exposed; NNRTI=non-nucleoside reverse transcriptase inhibitor; OLI=oral lead-in; PI=protease inhibitor; RAM=resistance-associated mutation; RPV=rilpivirine.

References:

  1. Ramgopal MN, Castagna A, Cazanave C, et al. Efficacy, safety, and tolerability of switching to long-acting cabotegravir plus rilpivirine versus continuing fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with HIV, 12-month results (SOLAR): a randomised, open-label, phase 3b, non-inferiority trial. Lancet HIV. 2023;10(9):E566-E577. doi.org/10.1016/S2352-3018(23)00136-4
  2. Data on file. ViiV Healthcare group of companies. Durham, NC.
  3. Eu B, Oka S, Sims J, et al. Cabotegravir + rilpivirine long-acting outcomes by sex at birth, age, race, and body mass index: a subgroup analysis of the phase 3b SOLAR study. Poster presented at: IAS Conference on HIV Science; July 23-26, 2023; Virtual and Brisbane, Australia. EPB0221.
  4. 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.

PMUS-CBRWCNT250025