To bnAb or not to bnAb?… How will bnAbs fit into the HIV treatment paradigm?
Initially studied as the holy grail of a humoral HIV vaccine response but now repurposed to make a comeback as a treatment for HIV, broadly neutralising antibodies (bnAbs) got one step closer to clinical practice today, as Gilead presented positive proof-of-concept data for its two bnAbs, teropavimab and zinlirvimab, at CROI 2023. Gilead reported promising tolerability and efficacy data from its Phase 1b trial, which sought to demonstrate that bnAbs when used in combination with lenacapavir (Gilead’s novel long-acting capsid inhibitor) can maintain virological suppression in people living with HIV (PLWH). Excitingly, 90% of trial participants (n=18) were able to maintain virological suppression at 26-weeks (6 months) post-treatment, following only a single administration of all three agents at Day 1 of enrollment and no subsequent oral ARV dosing. Not only do these data position teropavimab and zinlirvimab, in combination with lenacapavir, as a potentially therapeutically active complete drug regimen for the treatment for HIV, they also point to the possibility of a complete drug regimen with twice yearly dosing – which if successful, would remove the need for daily oral medication.
Many questions remain regarding the utility of bnAbs in HIV. Considering the stringent enrollment criteria for Gilead’s Phase 1b trial, it is yet to be seen if bnAbs can be used broadly across a wide group of patients, or if their clinical utility is limited to certain patient subsets (i.e., those patients who underwent complex resistance screening). Only larger randomised trials will provide these answers. Luckily Gilead is set to advance teropavimab and zinlirvimab to Phase 2 trials in combination with lenacapavir in the latter-half of 2023, so answers may soon be expected. Elsewhere, ViiV/GSK’s GSK3810109A (bnAb) reported strong viral efficacy when dosed as a monotherapy in the Phase 2a BANNER trial which enrolled treatment-naïve HIV-positive adults; collectively this gives further weight to the possibility of bnAbs becoming a new MOA for multiple stages of HIV clinical management.
