FLAIR: Monthly Cabotegravir + Rilpivirine Non-Inferior to DTG/ABC/3TC at 48 Weeks

The 48-week results of the FLAIR study indicate that the regimen of a monthly injection of long acting cabotegravir/rilpivirine is non-inferior to a regimen of oral dolutegravir/abacavir/lamivudine (DTG/ABC/3TC).

Detailed findings of the study were presented in an oral abstract presentation at the Annual Conference on Retroviruses and Opportunistic Infections (CROI 2019).

In an exclusive interview Contagion® spoke to Brian Woodfall, MD, global head of development at Janssen, about the new data (see video).

"The FLAIR and the ATLAS trials were 2 phase 3 trials of long-acting injectable cabotegravir plus rilpivirine and the really amazing thing about both of them is that they really tested a completely new paradigm in the treatment of HIV infection." Dr. Woodfall said.

"These are the first trials that have tested a regimen that provides the opportunity for more infrequent dosing. So, in this case an injection of each of those 2 antiretrovirals once a month," Dr. Woodfall added.

First Long-Acting Injectable Regimen (FLAIR) was designed to evaluate the 2-drug long-acting injectable regimen of the integrase strand transfer inhibitor (INSTI) cabotegravir and nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine. The investigational long-acting injectable is being developed to reduce dose frequency, pill taking, and drug exposures that are typical of current HIV treatment regimens.

For the phase 3, open-label, multicenter study, patients with HIV who were antiretroviral therapy treatment (ART)-naïve received induction therapy with oral DTG/ABC/3TC for 20 weeks. The participants with HIV 1- RNA <50 c/mL at 16 weeks were eligible to enter the maintenance phase of the trial. The trial enrolled 566 participants who were randomly assigned 1:1 to continue current therapy or switch to the long-acting injectable therapy.

At induction phase start, the median CD4 count was 444 cells/mm³, median VL was 4.4 log₁₀ c/mL. The median age of the trial participants was 34 years, 22% were female and 74% were white.

The 283 participants in the long-acting arm received an oral lead in of 30 mg of cabotegravir + 25 mg of rilpivirine once daily for 4 weeks to evaluate tolerability, before receiving cabotegravir/rilpivirine as an intramuscular long-acting injectable therapy.

Six participants in the cabotegravir/rilpivirine arm (2.1%) and 7 in the DTG/ABC/3TC arm (2.5%) met the primary endpoint of viral load >50 c/mL at 48 weeks by US Food and Drug Administration snapshot algorithm (non-inferiority margin 6%).

Secondary endpoints included safety, tolerability, and confirmed virologic failure. The investigators indicate that the key secondary endpoint of HIV-1 RNA <50 c/mL was achieved by 93.6% of the cabotegravir/rilpivirine arm and 93.3% of the DTG/ABC/3TC arm.

Confirmed virologic failure was observed in 4 participants (1.4%) in the cabotegravir/rilpivirine; 3 had mutations in the NNRTI + INSTI domains and 1 was not tested. In the DTG/ABC/3TC arm, 3 confirmed virologic failures, none of which had INSTI resistance.

Among the participants in the cabotegravir/rilpivirine arm, the most common adverse event was injection site reactions, which were reported in 82% of the enrolled participants. The injection site reactions decreased in frequency over time, with 99% categorized as grade 1 or 2 events, with a median duration of 3 days.

The investigators also noted that of the 263 cabotegravir/rilpivirine arm participants completing an HIV Treatment Satisfaction Questionnaire at week 48, 99% reported being more satisfied with long-acting cabotegravir and rilpivirine compared with daily oral treatment.

The 48-week results of ATLAS indicate that the long-acting regimen of cabotegravir/rilpivirine was non-inferior to DTG/ABC/3TC and generally well tolerated, with few serious adverse events.

“Overall these results demonstrated the therapeutic potential of CAB+RPV injections, following short initial induction with oral DTG/ABC/3TC to achieve viral suppression,” the investigators concluded.

The study, “Long-Acting Cabotegravir + Rilpivirine for HIV Maintenance: FLAIR 48 Week Results,” was presented at the Annual Conference on Retroviruses and Opportunistic Infections (CROI), held March 4-7, 2019, in Seattle, Washington.