CROI 2025: N6LS: 4-monthly injectable bNAb with monthly injectable cabotegravir
18 March 2025. Related: Conference reports, Antiretrovirals, CROI 32 San Francisco 2025.
Simon Collins, HIV i-Base
The phase 2b EMBRACE study randomised 125 people (2:2:1) who were already undetectable on current ART to one of two different formulations of the bNAb N6LS every four months plus monthly cabotegravir IM or to maintain current ART as the standard of care.
N6LS was either given in a 60 mg/kg IV infusion (Arm 1, n=50) or as a 3000 mg SC injection with rHuPH20 (Arm 2, n=49) which creates a slow-release depot. The control arm was current ART (Arm 3, n=25).
Median age was 47 (range 25 to 68), 83% were men, 63% were white and median BMI was 28 (range: 17 to 40).
The primary endpoint of viral load >50 copies/mL at month 6 was reported for 4, 6 and 0 participants, with missing data for 0, 6 and 4 participants in Arms 1, 2 and 3 respectively. The lead to 96%, 88% and 96% with undetectable viral load, respectively.
Two participants in Arm 1 experienced viral failure, both with reduced sensitivity to N6LS. Two participants experienced viral failure in Arm 2 retained sensitivity to the bNAb but one developed Q148R integrase mutation but retained sensitivity to dolutegravir. All resuppressed after switching back to oral ART.
Tolerability was generally good but the higher rate of injection site reactions and other mild side effects in Arm 2 led to the decision to continue development of N6LS using the IV formulation used in Arm 1.
The second phase of the EMBRACE study will give N6LS every six months.
N6LS is being developed by ViiV Healthcare with the compound name VH3810109 (VH-109).
comment
It is good that N6LS is supported by data to extend dosing to every six months. Details about dosing intervals for cabotegravir in the second phase of the study were not reported.
The strategy of using rHuPH20 was also previously studied to extend the dosing interval for cabotegravir but this approach was also discontinued last year. [2]
References
- Leone P et al. VH3810109 (N6LS) Efficacy and safety in adults who are virologically suppressed: the EMBRACE study. CROI 2025. Oral abstract 203.
https://www.croiconference.org/abstract/3807-2025/ (abstract)
https://watch.croiwebcasts.org/2025croi/ap/54369 (webcast with registration) - ViiV Healthcare presents phase 1 clinical trial findings of a cabotegravir long-acting injectable investigational formulation allowing at least four months between doses. (4 March 2024).
https://viivhealthcare.com/hiv-news-and-media/news/press-releases/2024/march/cabotegravir-long-acting-injectable/