Teropavimab (GS-5423): A Comprehensive Clinical and Scientific Monograph on a Novel Broadly Neutralizing Antibody for Long-Acting HIV-1 Therapy

Executive Summary & Key Insights

Teropavimab is an investigational, long-acting, broadly neutralizing antibody (bNAb) at the forefront of a potential paradigm shift in the management of Human Immunodeficiency Virus Type 1 (HIV-1) infection. It is a central component of an innovative, twice-yearly injectable antiretroviral regimen, which combines Teropavimab with a second bNAb, zinlirvimab, and the first-in-class capsid inhibitor, lenacapavir. This tripartite combination, referred to as the LTZ regimen, represents a significant evolution in antiretroviral therapy, aiming to drastically reduce the treatment burden for people living with HIV.

Clinical development has demonstrated the regimen's high efficacy. Primary results from a pivotal Phase 2 study (NCT05729568) established that the twice-yearly LTZ regimen is non-inferior to a continuous daily oral antiretroviral regimen in maintaining virologic suppression over 26 weeks. Suppression rates were nearly identical between the groups, with 96.2% of participants in the LTZ arm and 96.3% in the daily oral therapy arm maintaining an HIV-1 RNA level below 50 copies/mL.[1] The regimen has been generally well-tolerated, with a safety profile characterized predominantly by mild-to-moderate, manageable injection site reactions associated with the subcutaneous administration of lenacapavir. A notable safety finding has been the absence of significant infusion-related reactions to the intravenously administered Teropavimab and zinlirvimab, a positive outcome for biologic-based therapies.[1] In recognition of its potential for substantial improvement over available therapies, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to the investigational combination in January 2025.[3]