ViiV Healthcare announced positive results from its phase IIb EMBRACE study, showing that N6LS (VH3810109 or VH109), a broadly neutralizing antibody (bNAb), effectively maintained viral suppression in adults living with HIV when administered every four months in combination with monthly cabotegravir long-acting (CAB LA). The findings were presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2025) in San Francisco.
The study evaluated N6LS in participants who were already stable on HIV treatment. At the six-month primary endpoint, 96% of participants receiving N6LS 60mg/kg intravenously (IV) and 88% receiving N6LS 3000mg subcutaneously (SC) with rHuPH20 maintained HIV-1 RNA levels below 50 copies/mL, compared to 96% in the standard-of-care group.
"As leaders in long-acting injectable innovation, we are building on the positive patient and physician experience we have with Cabenuva and pioneering the next generation of long-acting treatment options," said Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare. "The EMBRACE study demonstrated that VH109, a CD4-binding broadly neutralising antibody, administered every four months with cabotegravir, achieved high efficacy and was well tolerated through six months."
Safety and Tolerability Profile
The safety data showed that N6LS was generally well tolerated across both administration routes. However, infusion site reactions were more frequent with subcutaneous administration, occurring in 14% of SC participants compared to none with IV administration.
Adverse events related to study medication were reported in 64% of the IV group and 65% of the SC group. Notably, 16% of participants in the SC group experienced grade 3-4 adverse events (erythema), while no participants in the IV group reported severe adverse events.
Confirmed virologic failure was observed in two participants from each N6LS treatment group. Overall, 4% of the IV group and 6% of the SC group had HIV-1 RNA levels of 50 copies/mL or higher at month six, compared to none in the standard-of-care group.
Mechanism of Action and Treatment Context
N6LS is a CD4-binding broadly neutralizing antibody that targets the HIV virus through a different mechanism than traditional antiretrovirals. This novel approach could provide an important component for future long-acting HIV treatment regimens.
The current standard of care for long-acting HIV treatment, Cabenuva, combines cabotegravir, an integrase strand transfer inhibitor (INSTI), with rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI). INSTIs work by preventing viral DNA from integrating into the genetic material of human immune cells, while NNRTIs interfere with reverse transcriptase to stop viral replication.
The addition of broadly neutralizing antibodies like N6LS to existing treatment approaches represents a significant advancement in HIV therapy, potentially allowing for less frequent dosing schedules and improved treatment adherence.
Future Development Plans
Based on the favorable results observed in the EMBRACE trial, ViiV Healthcare plans to progress development of a six-month IV formulation of N6LS in combination with CAB LA for further evaluation in the second part of the EMBRACE trial.
This development aligns with the company's strategy to create "ultra long-acting regimens" that could further reduce treatment burden for people living with HIV. If successful, such regimens could potentially transform HIV care by significantly extending the time between treatments.
ViiV Healthcare, majority owned by GSK with Pfizer and Shionogi as shareholders, continues to focus on developing innovative HIV treatments and prevention options. The company has established itself as a leader in long-acting injectable therapies for HIV, with Cabenuva already approved for treatment of HIV-1 infection in adults and adolescents 12 years and older who meet specific criteria.
The positive results from the EMBRACE study add to the growing body of evidence supporting N6LS as a potent antiviral that can function as a component of a complete antiretroviral regimen, potentially offering people living with HIV new treatment options with extended dosing intervals.
