ViiV Healthcare’s Experimental Antibody N6LS Shows Promise in Long-Acting HIV Treatment
A new study from ViiV Healthcare has demonstrated that its investigational broadly neutralizing antibody (bNAb), N6LS (VH3810109 or VH109), effectively maintains viral suppression in individuals living with HIV when combined with long-acting cabotegravir (CAB-LA). Findings from the Phase IIb EMBRACE study indicate that N6LS, administered every four months, is a potent antiviral that could serve as part of a long-acting HIV treatment regimen.
Key Findings from the EMBRACE Study
The EMBRACE trial enrolled participants with stable HIV treatment histories to assess the efficacy of VH109 in combination with CAB-LA. At the six-month primary endpoint, the study reported:
96% of participants receiving VH109 60 mg/kg intravenously (IV) and 88% receiving VH109 3000 mg subcutaneously (SC) (with rHuPH20) maintained HIV-1 RNA levels below 50 copies/mL, comparable to the 96% in the standard-of-care group.
Confirmed virologic failure was recorded in two participants from each VH109 group.
HIV-1 RNA levels of 50 copies/mL or higher were detected in 4% of the IV group and 6% of the SC group, whereas no participants in the standard-of-care group exhibited similar levels at month six.
Cabenuva is an FDA-approved, complete regimen for treating HIV-1 in adults and adolescents (aged 12 and older, weighing at least 35kg) who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen, with no prior treatment failure or resistance to cabotegravir or rilpivirine.
ViiV Healthcare Advances Long-Acting HIV Treatment Innovations with Promising New Data at CROI 2025
ViiV Healthcare continues to push the boundaries of HIV treatment innovation, presenting encouraging findings at the Conference on Retroviruses and Opportunistic Infections (CROI 2025) in San Francisco. The latest data highlights two investigational antiretroviral therapies—VH4524184 (VH184), a third-generation integrase inhibitor (INSTI), and VH4011499 (VH499), a potent capsid inhibitor. Both compounds demonstrated strong antiviral activity and favorable safety profiles, reinforcing their potential as long-acting injectable treatments for HIV.
VH184 Shows Strong Antiviral Activity and Safety
A recent Phase IIa proof-of-concept study evaluated VH184’s efficacy and safety across multiple dosage levels in 22 adults living with HIV-1 who had not received prior antiretroviral therapy. Participants, all with an HIV-1 RNA level of at least 3000 copies/mL, were administered three different doses of VH184 (10mg, 50mg, and 300mg) every three days over a 10-day monotherapy period.
Results demonstrated a significant reduction in HIV-1 viral load across all doses. Average decreases in viral load were recorded as follows:
10mg dose: -1.17 log10 copies/mL
50mg dose: -2.15 log10 copies/mL
300mg dose: -2.31 log10 copies/mL
The most substantial decline, reaching -2.69 log10 copies/mL, was observed in the 300mg group. Notably, no drug resistance mutations emerged during the study, and all reported side effects were mild to moderate, with no participants discontinuing treatment due to adverse events.
Ongoing research includes a Phase I study assessing long-acting formulations of VH184 in adults without HIV, supporting further development of this compound as a potential next-generation injectable therapy.
VH499 Demonstrates Promising Capsid Inhibitor Potential
Another Phase IIa study investigated VH499, a highly potent capsid inhibitor, in 23 treatment-naïve adults with HIV-1 RNA levels of at least 3000 copies/mL. The study assessed the antiviral effects of three oral dosage levels (25mg, 100mg, and 250mg) over an 11-day period.
All doses resulted in a reduction in viral load:
25mg and 100mg doses: -1.8 log10 copies/mL
250mg dose: -2.2 log10 copies/mL
VH499 was well tolerated, with all adverse events classified as mild to moderate. No participants withdrew due to side effects, and no serious adverse events were reported. However, one individual in the 25mg group exhibited a mutation associated with reduced susceptibility to capsid inhibitors.
Biktarvy Continues to Show Strong Viral Suppression in HIV/HBV Coinfection
New data from the ongoing Phase 3 ALLIANCE study evaluated the effectiveness of Biktarvy compared to a regimen of dolutegravir (DTG) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) in adults newly diagnosed with both HIV and HBV. The trial, which is the first randomized study comparing TAF-based and TDF-based regimens in this population, aims to determine the most effective treatment approach for managing both viruses simultaneously.
Results from the open-label extension phase, following 96 weeks of treatment, demonstrated that Biktarvy maintained high rates of viral suppression. Among participants who switched to Biktarvy, 95.4% achieved HIV-1 suppression (HIV RNA <50 copies/mL), while 86.6% maintained HBV suppression (HBV DNA <29 IU/mL).
Treatment-related adverse events were reported in 19% of participants, but most were mild to moderate. No participants discontinued treatment due to side effects. The most frequently reported side effects included weight gain (9%) and an increase in low-density lipoprotein (LDL) cholesterol (3%).
FDA Grants Breakthrough Therapy Designation to New Long-Acting Injectable Regimen
A major milestone in HIV treatment innovation was achieved when the FDA awarded Breakthrough Therapy Designation to an investigational long-acting regimen combining lenacapavir (LEN) with two broadly neutralizing antibodies (bNAbs), teropavimab (TAB) and zinlirvimab (ZAB). This designation is given to therapies that show significant potential to improve treatment outcomes over existing options.
This investigational regimen, known as LEN+TAB+ZAB (LTZ), is being developed as a twice-yearly injectable treatment. If approved, it could become the first long-acting combination therapy offering extended dosing intervals, providing a new option for people living with HIV.
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