New drug on the horizon for treating adenovirus

Area of Science:

• Virology
• Immunology
• Pharmacology

Background:

• Human adenoviruses cause life-threatening disseminated infections in immunosuppressed individuals, particularly pediatric allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients.
• Current treatment options are limited, with no approved drugs specifically for adenovirus infections, although intravenous cidofovir is used off-label.
• Cidofovir, an effective antiviral agent, suffers from poor cellular uptake and significant nephrotoxicity.

Discussion:

• Brincidofovir, an orally administered lipid-linked cidofovir derivative, demonstrates broad-spectrum activity against double-stranded DNA viruses, including adenoviruses.
• It exhibits improved cellular uptake and intracellular conversion to cidofovir, bypassing the nephrotoxicity associated with the parent drug.
• The ongoing AdVise Study (Phase III) is evaluating brincidofovir's efficacy and safety in transplant patients with adenovirus infections.

Key Insights:

• Preliminary AdVise Study results suggest brincidofovir is safe and highly effective in reducing adenovirus viremia.
• Brincidofovir significantly decreases adenovirus-induced pathogenicity and mortality in transplant recipients.
• The oral administration and improved safety profile of brincidofovir represent a major therapeutic advance.

Outlook:

• Brincidofovir is poised to become a crucial therapeutic option for managing adenovirus infections in immunocompromised patients.
• Further clinical evaluation will solidify its role in post-transplant care and other immunosuppressed populations.
• Adoptive T cell therapy targeting adenoviruses also presents a promising complementary or alternative strategy for allo-HSCT patients.