brincidofovir

Brincidofovir, also known as CMX001, is an oral lipid-conjugated prodrug of cidofovir developed for broad-spectrum antiviral activity against double-stranded DNA viruses. It was studied for conditions such as cytomegalovirus (CMV) infection and prophylaxis in immunocompromised patients, and was also explored for orthopoxvirus infections in biodefense research.

Mechanism and pharmacology

Brincidofovir is designed to improve oral bioavailability and cellular delivery of cidofovir. After administration, the lipid moiety facilitates uptake into cells, where the compound is converted to cidofovir monophosphate and then to cidofovir diphosphate, the active metabolite. This active form inhibits viral DNA polymerase and suppresses viral replication.

Spectrum and indications

In preclinical and clinical studies, brincidofovir showed activity against several dsDNA viruses, including CMV, adenovirus, herpesviruses, BK virus, and orthopoxviruses. It was studied as a potential prophylactic and therapeutic agent in allogeneic hematopoietic stem cell transplant recipients and other immunocompromised populations, and it was also evaluated in biodefense contexts for orthopoxvirus threats.

Clinical development and status

Development of brincidofovir for CMV and related indications did not advance to regulatory approval. Regulators did not approve the product based on available trial results, and further development in major indications was largely halted. Research has since shifted away from brincidofovir for clinical use, though the compound remains of historical interest as a prodrug approach to cidofovir.

Adverse effects and safety

Clinical trials reported gastrointestinal adverse events such as diarrhea and nausea, along with other general tolerability concerns. As with other nucleoside analogs, safety monitoring was a focus in trials, but, overall, the risk-benefit profile did not support approval for the studied indications.