The virus entry inhibitor ARN-75039 provides therapeutic protection against Lassa virus infection in guinea pigs

  • Sci Transl Med. 2026 Apr 15;18(845):eadx0938. doi: 10.1126/scitranslmed.adx0938.
Elizabeth Eudy  1 ,  Daniel Woodburn  1 ,  Rebecca Reeder  1 ,  Kurt Cooper  1 ,  Randy Hart  1 ,  Amanda Hischak  1 ,  Brett Eaton  1 ,  John B Ruedas  2 ,  Tung Tran  2 ,  Craig Johnson  2 ,  Russell Byrum  1 ,  Michael Holbrook  1 ,  Greg Henkel  2 ,  Ken McCormack  2 ,  Manu Anantpadma  1
Affiliations
  • 1. Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA.
  • 2. Arisan Therapeutics, Carlsbad, CA, USA.
PMID: 41984932 DOI: 10.1126/scitranslmed.adx0938
Abstract

Lassa virus (LASV), a member of the Arenaviridae family, causes Lassa fever. There are no vaccines available for prevention of Lassa fever, and the primary therapeutic for treatment (ribavirin) has questionable Antiviral activity and no formal approval for use. Here, we evaluated ARN-75039, an orally bioavailable broad-spectrum mammarenavirus entry inhibitor, against LASV Infection in outbred Hartley guinea pigs exposed to a guinea pig-adapted LASV. ARN-75039 was administered for 14 days either 3 or 7 days postexposure (dpe) to LASV. In the first two studies, once-daily dosing at 3 dpe provided protection against lethal Infection. A third study with twice-daily dosing at 7 dpe also achieved protection. Both drug regimens offered 100% protection at the lowest tested doses of 3.75 mg/kg (once-daily administration) or 7.5 mg/kg (twice-daily administration). ARN-75039-treated Animals exhibited minimal disease signs and undetectable viremia. These results suggest that ARN-75039, for which a phase 1 human clinical trial has now been completed, may offer robust protection against LASV Infection.

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