NPP-669, a prodrug of cidofovir, is highly efficacious against human adenovirus infection in the permissive Syrian hamster model

• Published in: Antimicrobial agents and chemotherapy Vol. 68; no. 7; p. e0048924
• Main Authors: Tollefson, Ann E, Cline-Smith, Anna B, Spencer, Jacqueline F, Reyna, Dawn M, Lipka, Elke, Toth, Karoly
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 09.07.2024
• Subjects: Antimicrobial Chemotherapy; Antiviral Agents; prodrug; in vivo; animal model; adenovirus; antiviral
• ISSN: 0066-4804; 1098-6596; 1098-6596
• DOI: 10.1128/aac.00489-24

Human adenoviruses can cause serious, disseminated infections in immunocompromised patients. For pediatric allogeneic stem cell transplant patients, the case fatality rate can reach 80%. Still, there is no available antiviral drug that is specifically approved by the Food and Drug Administration for the treatment of adenovirus infections. To fill this pressing medical need, we have developed NPP-669, a prodrug of cidofovir with broad activity against double-stranded DNA viruses, including adenoviruses. Here, we report on the anti-adenoviral efficacy of NPP-669. Using the immunosuppressed Syrian hamster as the model, we show that NPP-669 is highly efficacious when dosed orally at 1 mg/kg and 3 mg/kg. In a delayed administration experiment, NPP-669 was more effective than brincidofovir, a similar compound that reached Phase III clinical trials. Furthermore, parenteral administration of NPP-669 increased its efficacy approximately 10-fold compared to oral dosing without apparent toxicity, suggesting that this route may be preferable in a hospital setting. Based on these findings, we believe that NPP-669 is a promising new compound that needs to be further investigated.