Current status of LA/ER Cabotegravir and Rilpivirine
including pipeline report on novel CBT formulations
Speaker: William Spreen, Leader of Cabotegravir Medicine Development at ViiV Healthcare
Presented lessons learned during development of the LA ARVs, Cabotegravir (CAB) and Rilpivirine (RPV), which has resulted in several marketing approvals for HIV treatment and prevention (Canada March 2020; EU Dec 2020; US Jan 2021; and Australia Feb 2021).
Combination LA CAB and LA RPV IM is safe, tolerable, acceptable and effective to maintain virologic suppression up to 96 weeks.
In three Phase 3 non-inferiority studies comparing LA CAB/RPV to oral antiretroviral therapy (ART) – ATLAS, FLAIR and ATLAS-2M -- efficacy was non-inferior. LAI CAB as monotherapy for PrEP has clear, early superiority over oral ART – HPTN 083 and 084.
Oral lead in could be optional in the future.
No significant safety issues were observed among >90,000 CAB injections and >60,000 RPV cumulative injections, and direct-to-inject and oral-lead-in groups had similar safety, tolerability and efficacy during the Phase 3 extension of FLAIR and ATLAS-2M.
LA therapy was successfully continued during the pandemic.
Only 7% of participants missed an injection visit from 1 Dec 2019 to 15 Sep 2020, and these patients were successfully bridged with oral ART.
Real-world data will be needed to define the risk of developing resistance during the CAB PK tail following LA CAB for PrEP.
HPTN 083 and 084 data from 3 incident tail-phase HIV infections are encouraging (data to be presented at CROI 2021).
Future of LA CAB development.
A microarray patch for LA HIV PrEP (in collaboration with the PATH organization); a double-strength formulation to reduce injection volumes and allow self-administration (NCT04484337); and a CAB implant (in collaboration with Northwestern University).