Cabotegravir 4-monthly, also called CAB-ULA (ultra long-acting) is an  investigational longer-acting formulation of cabotegravir that demonstrates a pharmacokinetic (PK) profile supporting dosing intervals of approximately four months. This extended dosing schedule has the potential to reduce clinic visits and improve adherence. Early data suggest a favourable safety profile, with intramuscular (IM) administration being better tolerated than subcutaneous (SQ) injection. As a result, CAB-ULA IM dosed every four months is advancing into late-stage studies investigating its use for both HIV-1 PrEP and treatment.

For PrEP, the EXTEND 4M registration trial is evaluating a single IM injection of CAB-ULA at 1600 mg/3mL. The FDA has approved this registration strategy, based on PK bridging studies, without requiring an additional efficacy study. The trial was launched in December 2024 and is expected to reach its primary endpoints by Q3 2026.

For HIV treatment, a phase III registration trial is evaluating CAB-ULA combined with rilpivirine (RPV) at Q4M dosing, following the completion of phase I studies on multiple formulations.

Primary patents on cabotegravir have been granted in many LMICs and are expected to expire in 2026. A secondary patent on the 4-monthly formulation was published in March 2025. The corresponding international patent application is pending, and geographical coverage in LMICs is expected to be available by March 2026, with patents anticipated to expire in 2043.

Cabotegravir 4 monthly on LAPaL

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