EACS 2025: Investigational HIV broadly neutralizing antibody N6LS shown safe, tolerable in Phase 2b trial

Researchers have posted good results showing favorable tolerability, few infusion site reactions (ISRs), and no serious drug-related adverse events (AEs) of the phase 2b trial of the investigational ultra–long-acting broadly neutralizing antibody N6LS (VH3810109, ViiV Healthcare) at EACS 2025, in Paris.

“Overall, we’re pleased with the results,” Kimberly Smith, MD, MPH, the head of research and development at ViiV Healthcare, told Infectious Disease Special Edition. “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. Both intravenous and subcutaneous routes were well tolerated, but the overall assessment favored IV—which is why we’re now progressing with a six-month IV dosing schedule in the next phase of the study. These results reinforce VH109’s potential as a component of a future ultra long-acting HIV therapy options.”

The investigators enrolled 125 virologically suppressed participants with HIV who were mostly male (83%) and white (63%) and had a median age of 53 years (abstract PS09.1). Participants had a CD4+ cell count of at least 350 cells/mm3 and were on stable antiretroviral therapy for at least six months prior to the study. The investigators randomized participants to three groups: one receiving IV N6LS at 60 mg/kg, one receiving subcutaneous N6LS 3,000 mg plus recombinant human hyaluronidase PH20, and one receiving oral standard-of-care antiretroviral therapy.

Good Safety and Tolerability Profiles

The investigators reported that N6LS, both administered via IV or subcutaneously, had good safety and tolerability in the study population. Only two participants withdrew due to drug-related AEs, both in the subcutaneous arm. There were no serious drug-related AEs. The most common AEs reported were fatigue and headache.

They also found that there were no clinically meaningful findings in laboratory tests related to the study drug and no trend in changing CD4+ counts or CD4+/CD8+ ratios.

Low ISRs

The findings were similar in terms of ISRs. There were no serious drug-related ISRs, and no patients withdrew due to ISRs. Of all ISRs, fewer events were reported in the IV administration group than the subcutaneous group (IV: n=4 events in 4/50 participants; SC: n=70 events in 25/49 participants).

Participants reported the drug administration to be very tolerable, with “very acceptable” or “totally acceptable” sleep and physical impact at day 1 and month 4. Similarly, they rated their pain to be low following drug administration.

These positive findings mean research will continue, according to the researchers. “From both a participant experience and tolerability standpoint, N6LS was deemed highly acceptable, with few ISRs observed with IV administration,” the investigators wrote. “These data support the progression of IV N6LS administered twice yearly in part 2 of EMBRACE.”

Next steps are already in progress, Dr. Smith told IDSE. “We are initiating the second phase of the EMBRACE study, evaluating VH109 at a higher flat dose (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. We’re also continuing to explore the broader potential of bNAbs—not only in treatment, but also in prevention and possibly long-term remission—as part of our commitment to advancing innovative HIV care.”

By Meaghan Lee Callaghan