ViiV Healthcare's N6LS Broadly Neutralizing Antibody Shows Promise in Phase 2b HIV Trial
Key Insights
ViiV Healthcare's investigational broadly neutralizing antibody N6LS (VH3810109) demonstrated favorable safety and tolerability in the phase 2b EMBRACE trial when administered every four months with cabotegravir long-acting.
The study enrolled 125 virologically suppressed HIV (search) participants and showed successful viral suppression maintenance with both intravenous and subcutaneous routes, though IV administration was favored due to fewer infusion site reactions.
Based on positive results, ViiV Healthcare is advancing to the next phase with a six-month IV dosing schedule at 6000 mg, aiming to reduce treatment burden for people living with HIV (search).
ViiV Healthcare's investigational broadly neutralizing antibody N6LS (VH3810109) has demonstrated favorable safety and tolerability in the phase 2b EMBRACE trial, successfully maintaining viral suppression in HIV (search) patients when administered every four months in combination with cabotegravir long-acting. The results, presented at EACS 2025 in Paris, support the progression of this ultra-long-acting therapy to the next phase of development.
Study Design and Population
The EMBRACE phase 2b study enrolled 125 virologically suppressed participants with HIV (search) who were predominantly male (83%) and white (63%) with a median age of 53 years. Participants had CD4 (search)+ cell counts of at least 350 cells/mm³ and were on stable antiretroviral therapy for at least six months prior to enrollment. The investigators randomized participants into three groups: intravenous N6LS at 60 mg/kg, subcutaneous N6LS 3,000 mg plus recombinant human hyaluronidase PH20, and oral standard-of-care antiretroviral therapy.
Safety and Tolerability Results
N6LS demonstrated good safety and tolerability profiles across both administration routes. Only two participants withdrew due to drug-related adverse events, both from the subcutaneous arm. The study reported no serious drug-related adverse events, with the most common adverse events being fatigue and headache. Laboratory tests showed no clinically meaningful findings related to the study drug, and there were no trends in changing CD4 (search)+ counts or CD4+/CD8+ ratios.
Infusion Site Reactions Favor IV Administration
The study revealed significant differences in infusion site reactions between administration routes. The IV group experienced substantially fewer events (4 events in 4/50 participants) compared to the subcutaneous group (70 events in 25/49 participants). No serious drug-related infusion site reactions occurred, and no patients withdrew due to these reactions. Participants rated the drug administration as "very acceptable" or "totally acceptable" regarding sleep and physical impact at day 1 and month 4, with low pain scores following administration.
Clinical Efficacy and Future Development
"The EMBRACE phase 2b study demonstrated that our investigational broadly neutralizing antibody (bNAb), VH109 (also known as N6LS), successfully maintained viral suppression when administered every four months in combination with cabotegravir long-acting," said Kimberly Smith, MD, MPH, head of research and development at ViiV Healthcare. The overall assessment favored IV administration, leading to the decision to progress with a six-month IV dosing schedule in the next phase.
ViiV Healthcare is now initiating the second phase of the EMBRACE study, evaluating N6LS at a higher flat dose of 6000 mg IV every six months alongside long-acting cabotegravir every two months. This extended dosing interval aims to further reduce treatment burden and improve convenience for people living with HIV (search). The company continues to explore the broader potential of broadly neutralizing antibodies not only in treatment but also in prevention and possibly long-term remission strategies.