Phase III results from two trials demonstrated that the once-monthly combination of Johnson & Johnson's Edurant (rilpivirine) plus partner ViiV Healthcare's experimental integrase inhibitor cabotegravir met the primary endpoint of non-inferiority in maintaining viral suppression in adults with HIV-1, versus a daily oral three-drug regimen, the companies announced Thursday. John Pottage, chief scientific and medical officer at ViiV, remarked "we are also encouraged by patient preference data showing that nearly all participants who switched to the long-acting injectable regimen preferred it over their prior oral therapy." He added that the companies plan to submit applications to regulatory authorities later this year.
The findings, which were presented at the annual Conference on Retroviruses and Opportunistic Infections (CROI), suggest the two-drug combination may give patients "the option of managing their virus with just 12 injection regimens a year," commented Brian Woodfall, global head of development for infectious diseases at Johnson & Johnson's Janssen Pharmaceutica unit. "If approved by regulators, this will be the first monthly dosing solution for people living with HIV and represents a major step for HIV treatment," he added.
In the ATLAS trial, 616 virally suppressed adults with HIV were assigned to treatment with Edurant plus cabotegravir once every four weeks or continuing current oral antiretroviral therapy consisting of two nucleoside reverse transcriptase inhibitors and a third agent. Results showed that 1.6 percent of patients in the Edurant/cabotegravir arm exhibited plasma HIV-1 RNA levels of at least 50 copies per millilitre (c/mL) at week 48, compared to 1 percent of those in the three-drug arm.
In addition, virologic suppression rates in the two- and three-drug arms were 92.5 percent and 95.5 percent, respectively. Only three patients given the once-monthly injection developed confirmed virologic failure, with two of these found to have pre-existing non-nucleoside reverse transcriptase inhibitor resistance. The data also illustrated that 86.4 of patients in the Edurant/cabotegravir arm preferred the combination therapy, while 2.3 percent of those in the comparator group preferred their prior oral therapy.
Meanwhile, the FLAIR study assessed the two-drug combination in 566 virologically suppressed adults with HIV, following 20 weeks of induction therapy with ViiV's Triumeq (dolutegravir/abacavir/lamivudine). Participants were randomised to receive Edurant plus cabotegravir, injected every four weeks, or daily therapy with Triumeq. For the two-drug regimen, 2.1 percent of patients had plasma HIV-1 RNA levels of at least 50 c/mL at week 48, versus 2.5 percent for Triumeq.
Moreover, virologic suppression rates were 93.6 percent and 93.3 percent, respectively, in the two-drug combination and Triumeq groups. Three patients who received Edurant and cabotegravir exhibited confirmed virologic failure, with all three developing treatment-emergent integrase strand transfer inhibitor and non-nucleoside reverse transcriptase inhibitor resistance. In total, 90.8 percent of patients in the Edurant/cabotegravir arm preferred the long-acting combination regimen, with 0.7 percent of those in the comparator group preferring their prior oral regimen.
ViiV previously confirmed that both the ATLAS and FLAIR trials had achieved their primary endpoints. The company is also assessing the combination of Edurant and cabotegravir administered once every two months in the ongoing ATLAS-2M trial. GlaxoSmithKline, which holds a majority stake in ViiV with Pfizer and Shionogi as shareholders, previously identified cabotegravir as one of as many as 20 drugs that could be submitted for regulatory approval before 2020.
Currently, Gilead Sciences dominates the HIV market with a 53-percent share, compared to 22 percent for GlaxoSmithKline. However, Pottage noted that "although we're not privy to [Gilead's] internal workings…we don't see any studies coming from them with a two-drug regimen."
Edurant, a non-nucleoside reverse transcriptase inhibitor, was approved by the FDA in 2011 for use in combination with other antiretrovirals for the treatment of HIV-1 infection in previously untreated adults.
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