UK-based ViiV Healthcare and GSK announced positive final data from the Phase III LATITUDE trial evaluating Cabenuva (cabotegravir and rilpivirine) in individuals with HIV-1 who have a history of antiretroviral treatment adherence challenges. The trial met its primary endpoint, demonstrating superior efficacy in maintaining viral load suppression compared to daily oral therapy. This outcome provides validated clinical evidence for an alternative long-acting treatment modality in a patient population where daily pill burdens present a barrier to sustained care. The asset is an injectable combination of an integrase strand transfer inhibitor (INSTI) and a non-nucleoside reverse transcriptase inhibitor (NNRTI).
Trial specifics
The Phase III LATITUDE (Long-Acting Therapy to Improve Treatment Success in Daily Life) study was a randomized, open-label trial involving 453 participants facing daily oral adherence challenges or who had disengaged from HIV care. Participants first received guideline-recommended daily oral therapy to achieve viral suppression; the 306 participants who successfully suppressed the virus were then randomized to either receive the long-acting injectable combination every four weeks or continue daily oral therapy.
At the 48-week primary endpoint, the cumulative risk of regimen failure, defined as a combination of virologic failures and permanent treatment discontinuation, was reduced by nearly half to 22.8% for the long-acting arm compared to 41.2% for the daily oral therapy arm. Virologic failure occurred in 6.8% of the injectable group versus 28.2% in the oral group. The safety profile showed similar adverse event rates between both arms. Building on LATITUDE, the company is also conducting the ongoing CROWN study, which evaluates the long-acting regimen directly in individuals with adherence challenges and detectable virus.
Alongside this week’s press release, the 48-week data have been published to the New England Journal of Medicine. Notably, the trial’s independent Data and Safety Monitoring Board in February 2024 called for randomisation in the study to be halted and the long-acting regimen of Cabenuva to be made available to all study participants. ViiV Healthcare said these findings have the potential to validate a long-acting approach for this patient group.
Research context
Cabenuva targets two essential mechanisms in the HIV replication cycle: cabotegravir, an INSTI, prevents viral DNA from integrating into the genetic material of human T-cells, while rilpivirine, an NNRTI, interferes with the reverse transcriptase enzyme to stop the virus from multiplying. This dual mechanism sustains viral suppression without the need for daily oral administration, directly addressing the unmet need of treatment fatigue and adherence barriers. The asset is currently approved by the US FDA as a complete regimen for the treatment of HIV-1 infection in virologically suppressed adults and adolescents 12 years and older (weighing at least 35 kg) on a stable antiretroviral regimen with no history of treatment failure or known resistance.
While there are no direct, approved long-acting complete regimens of the exact same dual target class combination, key competitors in the broader long-acting HIV treatment landscape include:
• Gilead Sciences’ lenacapavir (Sunlenca), a first-in-class capsid inhibitor that is US FDA approved for multi-drug resistant HIV and is currently in Phase III development for broader treatment indications in long-acting combinations, differentiated by a twice-yearly subcutaneous administration.
• Merck & Co.’s islatravir, a nucleoside reverse transcriptase translocation inhibitor (NRTTI) advancing in Phase III trials for use in combination regimens, which differentiates itself by exploring once-weekly and once-monthly long-acting oral dosing rather than injectable delivery.
• Shionogi and ViiV Healthcare’s co-developed S-365598, an investigational third-generation INSTI currently in early-stage development intended to provide an ultra-long-acting dosing interval of three months or longer.