As HIV scientists push the boundaries of existing antiretroviral therapy (ART), an important new study finds that long-acting injectable cabotegravir/rilpivirine (CAB/RPV) works just as well when administered every two months, compared to once-monthly dosing.
Results of the ATLAS-2M study were presented Monday at the 2020 Conference on Retroviruses and Opportunistic Infections (CROI) by Edgar T. Overton, M.D., associate professor of medicine at the University of Alabama at Birmingham.
In prior clinical trials, the long-acting injection already proved to work just as well as oral ART among people who are already virologically suppressed. New data from the phase 3 FLAIR study, also presented at CROI, found that the injectable drug combo continued to be noninferior to oral three-drug dolutegravir/abacavir/lamivudine (Triumeq) after 96 weeks of treatment.
If approved, cabotegravir/rilpivirine would be the first long-acting injectable ART for HIV. Now, the results of ATLAS-2M are pushing the boundaries of how long it’s possible to wait in between injections. ATLAS-2M has important implications for treatment adherence, particularly because the overwhelming majority of patients prefer less-frequent dosing. Among patients who had experience with four-week and eight-week dosing, 94% preferred to receive the injection every other month.
The phase 3b ATLAS-2M study included 1,045 participants who received injectable long-acting cabotegravir/rilpivirine once every four weeks or once every eight weeks. Nearly three-fourths of the participants were cisgender men and white, and the median age of all participants was 42.
Thirty-seven percent of the study participants were transitioned from the prior ATLAS study, which was only testing the four-week dosing strategy. The rest of the participants had never before taken injectable long-acting cabotegravir/rilpivirine. Randomization was stratified according to each patient’s prior exposure to the study drug.
After 48 weeks of treatment, investigators concluded that the eight-week dosing was non-inferior to the four-week dosing, meaning that patients dosed less frequently had approximately equal outcomes in terms of viral suppression.
A handful of patients experienced virologic failure, including eight in the eight-week arm and two in the four-week arm. Of those who failed treatment, the vast majority had evidence of treatment-resistant mutations to either cabotegravir or rilpivirine.
In terms of safety, patients in the eight-week arm and the four-week arm saw a similar rate of adverse events. The majority were grade 1 adverse events, such as injection-site reactions. However, 2% of patients discontinued treatment because of adverse events (12 patients in the eight-week arm and 13 in the four-week arm), and just under half of those discontinuations were due to those injection-site reactions.
One of the patients in the study died of sepsis, but investigators determined this had nothing to do with the study drug.
For Overton, the results of ATLAS-2M highlight a promising new solution for patients who are looking for alternatives to daily oral ART. He pointed out that 98% of patients preferred long-acting injectable ART over oral therapy, and among those who had tried both four-week and eight-week dosing, 94% preferred less frequent injections.
“In summary,” he said, eight-week dosing of cabotegravir/rilpivirine is an “innovative and effective treatment for the maintenance of virologic suppression in people living with HIV.”
In the United States, rilpivirine is already approved in tablet form as Edurant. Cabotegravir is a new, investigational drug. The combination injectable formulation is being developed by Janssen (the maker of rilpivirine) and ViiV (the maker of cabotegravir).
In April of last year, the companies submitted for Food and Drug Administration approval of their long-acting injectable at a four-week dosing schedule, but in December, the FDA denied their application, citing manufacturing problems.
The companies continue to collect data on ongoing phase 3 trials, including ATLAS-2M, and continue to seek approval.