ATLAS and FLAIR efficacy: Once-monthly CABENUVA vs daily oral therapy
Once-monthly CABENUVA was studied in ATLAS and FLAIR, two robust, phase 3, noninferiority clinical trials1,2
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
FLAIR Trial Design2
- ≥18 years of age.1,2
- HIV-1 RNA <50 copies/mL.1
- Third agent included INSTI, NNRTI, or PI.1
- Oral lead-in regimen consisted of 30-mg cabotegravir and 25-mg rilpivirine once daily for at least 1 month.1,2
- 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
- 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
- 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:
- INSTI, NNRTI, or PI.1
- Or DTG + 2 NRTIs if HLA-B*5701- positive.2
- Baseline HIV-1 RNA measured prior to induction with abacavir/dolutegravir/lamivudine.4
- Patients with hepatitis B co-infection were excluded from the trials.2,3
- Two patients in FLAIR who were male at birth identified as transgender at enrollment.4
- Baseline race information was missing for 2 patients in the oral comparator arm in FLAIR.3
- 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
- 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
- CVF is defined as 2 consecutive plasma HIV-1 RNA ≥200 copies/mL3
- 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
- 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
- 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
- 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
- Or DTG plus 2 NRTIs if HLA-B*5701-positive.5
- CVF occurred at Week 64 with no resistance mutations.5
- One additional CVF was a patient who did not receive an injection dose of CABENUVA.5
3TC=lamivudine; ABC=abacavir; 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; NNRTI=non-nucleoside reverse transcriptase inhibitor; NRTI=nucleoside reverse transcriptase inhibitor; PI=protease inhibitor; W=Week.
References:
- 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
- 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
- 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.
- Data on file. ViiV Healthcare group of companies. Durham, NC.
- 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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