New Formulation of Cabotegravir for HIV Treatment Can be Dosed at Intervals of at Least 4 Months

Long-acting injectable therapies for HIV treatment have been an evolving modality that more companies are investigating, and have a variety of benefits including adherence, convenience, and it allows people with HIV (PWH) to stop thinking about their status every day. At this week’s ongoing Conference on Retroviruses and Opportunistic Infections (CROI) in Denver, CO, new data being reported shows a new ultra long-acting cabotegravir formulation doubles the current dosing interval. ViiV Healthcare reported this investigational HIV therapy can be dosed at intervals of at least 4 months.

“The HIV community has told us of their desire for longer-acting medicines that can help alleviate the burden of daily treatment,” Kimberly Smith, MD, MPH, Head of Research & Development at ViiV Healthcare, said in a statement. “This new formulation of cabotegravir (CAB-ULA) with a higher concentration and at least double the half-life puts us on the path toward delivering dosing at every four months for HIV treatment and PrEP.”

This data being reported at CROI is part of an ongoing, open-label, single-dose, dose-escalation phase 1 study in 70 healthy adults evaluated the safety and PK of 2 different formulations of cabotegravir and their potential for less frequent dosing. To evaluate the long-acting potential of these regimens, their PK profiles were compared against the 200 mg/mL intramuscular formulation of cabotegravir (CAB200), which is currently approved for the prevention of HIV by itself or for the treatment of HIV (when combined with rilpivirine).

One part of the study evaluated single doses of CAB-ULA administered subcutaneously (SC) in 16 participants or intramuscularly (IM) in 32 participants at doses of 800 mg, 1200 mg, and 1600 mg. The maximum observed plasma concentration of CAB ULA, regardless of route of administration, was lower than CAB200 IM at the same dose level, indicating slower absorption of CAB-ULA.

The projected half-life (measure of time the drug stays in the body) of CAB-ULA (SC) and CAB-ULA (IM) was six times greater and two times greater, respectively, than the half-life of CAB200 IM. PK simulations enabled researchers to predict that a 1600 mg/3mL IM dose of CAB-ULA administered every 4 months or greater could potentially achieve a similar level of medicine exposure compared to the approved 600 mg/3mL IM dose of CAB200, which is administered every 2 months.

In terms of safety, administration of CAB-ULA was well tolerated with no adverse events (AEs) leading to participant study discontinuation. All participants who received SC doses of CAB-ULA reported injection site reactions (ISRs), while 22/32 who received IM doses reported ISR events. The majority of IM ISRs were mild pain (grade 1) that lasted less than 7 days. Even though dosing in this study was higher than the currently approved CAB200 IM, the CAB-ULA IM ISR profile appeared comparable to the established CAB200 IM ISR profile.

Reference
ViiV Healthcare Presents Phase 1 Clinical Trial Findings of a Cabotegravir Long-Acting Injectable Investigational Formulation Allowinf at Least Four Months Between Doses. ViiV press release. March 4, 2024. Accessed March 4, 2024. https://viivhealthcare.com/hiv-news-and-media/news/press-releases/2024/march/cabotegravir-long-acting-injectable/