In short
Brincidofovir (Tembexa) is an antiviral medicine approved in the United States to treat human smallpox disease. It belongs to a group of drugs called nucleotide analog DNA polymerase inhibitors. One authorised Phase 3 trial (NCT07387367) is now testing an intravenous form of brincidofovir against intravenous cidofovir in 206 children and adults with adenovirus infection after a stem cell transplant.
Key points
- Brincidofovir is approved in the United States for treating human smallpox disease in adults and children, including newborns.
- The approved forms are 100 mg tablets and a 10 mg/mL oral suspension, given once weekly for two doses.
- One authorised Phase 3 trial is testing intravenous brincidofovir against intravenous cidofovir in 206 participants with adenovirus viremia after stem cell transplant.
- The trial's main measure is the proportion of participants with adenovirus virological success.
- The prescribing information carries a boxed warning about increased mortality when brincidofovir is used for longer durations in another disease.
- Brincidofovir is not indicated for diseases other than human smallpox disease.
What is brincidofovir?
Brincidofovir is an antiviral medicine sold under the brand name Tembexa. It is an orthopoxvirus nucleotide analog DNA polymerase inhibitor, which means it blocks a viral enzyme that the virus needs to copy its genetic material. The US Food and Drug Administration (FDA) approved brincidofovir in 2021 for the treatment of human smallpox disease in adults and children, including newborns. The drug was approved under the FDA's Animal Rule because adequate and well-controlled field trials in people with smallpox have not been feasible and inducing smallpox disease in humans to study the drug's efficacy is not ethical.
How does brincidofovir work?
Brincidofovir is a nucleotide analog that inhibits the viral DNA polymerase enzyme. By blocking this enzyme, the drug prevents orthopoxviruses such as the smallpox virus from copying their DNA and multiplying. The prescribing information notes that brincidofovir efficacy may be reduced in immunocompromised patients based on studies in immune-deficient animals.
Which conditions is it used or studied for?
- Human smallpox disease — brincidofovir is approved in the United States to treat smallpox in adults and children, including newborns.
- Adenovirus viremia after stem cell transplant — one authorised Phase 3 trial is testing intravenous brincidofovir against intravenous cidofovir in children and adults with adenovirus infection after an allogeneic haematopoietic cell transplant.
- Mpox infection — brincidofovir has been used off-label for mpox, and in vitro and animal studies have shown effectiveness against orthopoxviruses, but data in humans with mpox are not available.
How is brincidofovir given?
Brincidofovir is available as 100 mg film-coated tablets and as a 10 mg/mL oral suspension. The product information gives a dose of 200 mg once weekly for two doses for adults and children weighing 48 kg or more, 4 mg/kg oral suspension once weekly for two doses for those weighing 10 kg to less than 48 kg, and 6 mg/kg oral suspension once weekly for two doses for children weighing less than 10 kg. The authorised clinical trial is testing an intravenous infusion form of brincidofovir.
What do the clinical trials show?
The EU Clinical Trials Information System lists one authorised Phase 3 trial of brincidofovir, with a planned enrolment of 206 participants. The trial compares intravenous brincidofovir with intravenous cidofovir in children and adults who have adenovirus viremia after an allogeneic haematopoietic cell transplant. The main measure is the proportion of participants with adenovirus virological success. The trial is currently in the authorised status, meaning it has been approved but the registry does not yet report results.
What side effects are known?
The prescribing information carries a boxed warning that an increased incidence of mortality was seen in brincidofovir-treated subjects compared to placebo-treated subjects in a 24-week clinical trial when the drug was evaluated in another disease. The label also warns that brincidofovir may cause elevations in serum transaminases and bilirubin, and recommends hepatic laboratory testing before and during treatment.