Once-a-month HIV treatment sees promising phase III results

Janssen and ViiV have reported positive data for their once-monthly injectable HIV combo regimen in two phase III trials.

The combination of ViiV’s experimental integrase inhibitor cabotegravir and Janssen’s Edurant (rilpivirine), injected every four weeks, could change HIV treatment from 365 dosing days per year to just 12, noted John Pottage, ViiV’s chief scientific and medical officer.

Following an initial announcement of positive results last year, detailed data from the two trials has been presented at the annual Conference on Retroviruses and Opportunistic Infections (CROI).

The ATLAS study met its primary endpoint, with cabotegravir and Edurant demonstrating non-inferiority compared to a standard of care, daily, oral three-drug regimen.

Of those taking the two-drug regimen, 1.6% had plasma HIV-1 RNA levels of at least 50 copies per millilitre (c/mL) at week 48, compared to 1% in those taking current antiretroviral therapy.

Virologic suppression rates in the cabotegravir/Edurant and three-drug arms were 92.5% and 95.5% respectively, while only three patients taking the once-monthly treatment developed confirmed virologic failure, with two of these identified as having pre-existing non-nucleoside reverse transcriptase inhibitor resistance.

Another study, FLAIR, also met its primary endpoint with the once-monthly treatment demonstrating non-inferiority to ViiV’s Triumeq (abacavir/dolutegravir/lamivudine-ABC/DTG/3TC). 2% of patients on cabotegravir/Edurant had plasma HIV-1 RNA levels of at least 50 c/mL compared to 2.5% for the Triumeq patients.

As in the ATLAS study, virologic suppression rates were similar between both arms and CVF was infrequent.  

Pottage said that the company was also encouraged by patient preference data showing that nearly all participants in both studies who switched to the long-acting injectable regimen preferred it over their prior oral therapy.

Chloe Orkin, consultant physician and clinical professor at Queen Mary University of London and FLAIR principal investigator, added that the regimen “may provide an opportunity to change the paradigm for people living with HIV by breaking the cycle of a daily pill, which has been a defining characteristic of HIV therapy for several decades”.

The company is looking to submit regulatory applications later this year.

Its main rival in the space is Gilead, whose triple therapy strategy has led them to dominate the market – having a 52% share compared to ViiV’s 22%.

Gilead argues that meddling with this successful treatment formula could run the risk of lowering defenses to drug-resistant HIV.

At CROI the company announced positive phase I results from trials of its novel, long-acting capsid inhibitor GS-6207, as well as phase III data demonstrating non-inferiority for once-daily Descovy versus once-daily Truvada for PrEP, setting the drug up for approval in this indication.

ViiV is also investigating a formulation of cabotegravir and Edurant that can be administered every two months in the ATLAS-2M study.

The company recently scored FDA Priority Review for its single-tablet, two drug regimen of dolutegravir and lamivudine.