In short
Zinlirvimab is an investigational broadly neutralising antibody (bNAb) being studied for the treatment of HIV-1. It is given together with lenacapavir and teropavimab as part of a long-acting combination regimen. Two authorised Phase 3 trials are currently evaluating this combination in 590 adults each with virologically suppressed HIV-1.
Key points
- Zinlirvimab is a broadly neutralising antibody targeting HIV-1.
- It is studied in Phase 3 trials in adults with virologically suppressed HIV-1.
- Each trial enrols 590 participants.
- The combination includes lenacapavir and teropavimab, given as injections.
- The main measure is the proportion with HIV-1 RNA ≥ 50 copies/mL at Week 52.
What is zinlirvimab?
Zinlirvimab is an investigational broadly neutralising antibody (bNAb) being developed for the treatment of HIV-1 infection. It is not yet authorised as a medicine and is currently being evaluated in clinical trials. The substance is a protein-based antibody that targets the virus directly. In the trial records, zinlirvimab appears under the development code GS-5423.
How does zinlirvimab work?
Zinlirvimab belongs to a class of medicines called broadly neutralising antibodies. These antibodies are designed to recognise and attach to parts of the HIV-1 virus, helping the immune system to neutralise it. In the phase 2 study, zinlirvimab was combined with another bNAb called teropavimab and the antiretroviral lenacapavir. This combination was studied in people whose virus was highly susceptible to both antibodies, meaning the antibodies could neutralise their HIV-1 at low concentrations.
Which conditions is zinlirvimab studied for?
- HIV-1 infection — zinlirvimab is being studied in adults with HIV-1 who are already on antiretroviral therapy and have their virus under control (virologically suppressed).
How is zinlirvimab given?
In the clinical trials, zinlirvimab is given as an intravenous infusion at a dose of 3400 mg. It is administered together with lenacapavir, which is given as a subcutaneous injection, and teropavimab, which is also given intravenously. The aim of this combination is to provide a long-acting regimen that can be given twice a year.
What do the clinical trials show?
Two authorised Phase 3 trials are currently listed in the EU Clinical Trials Information System. Both trials enrol adults with HIV-1 who are virologically suppressed on their current oral antiretroviral therapy. Each trial plans to include 590 participants.
The first trial compares switching to the combination of lenacapavir, teropavimab and zinlirvimab against switching to the two-drug regimen of cabotegravir and rilpivirine. The second trial compares the same triple combination against continuing the participant's existing oral antiretroviral regimen.
The main measure in both trials is the proportion of participants with HIV-1 RNA of 50 copies per millilitre or higher at Week 52, using the US FDA snapshot algorithm. This measures whether the virus stays suppressed on the new regimen.
Earlier, a Phase 2 study evaluated the same combination. In that study, people received subcutaneous lenacapavir 927 mg with an oral loading dose, plus intravenous teropavimab 2550 mg and zinlirvimab 2550 mg given twice a year. The study compared this combination against continuing an oral stable baseline regimen. The Phase 1b study before it had shown that the combination maintained viral suppression for six months in people whose HIV-1 was highly susceptible to both antibodies.
What side effects are known?
The phase 2 study reported efficacy and safety results for the combination of lenacapavir, teropavimab and zinlirvimab. The published report describes the primary outcome results at week 26. Detailed side effect information from that study is available in the full publication.