General Information

Tembexa (brincidofovir) is an orthopoxvirus nucleotide analog DNA polymerase inhibitor.

Tembexa is specifically indicated for the treatment of human smallpox disease in adult and pediatric patients, including neonates.

Tembexa is suppled as tablets and an oral suspension for oral administration. The recommended dosing and administration schedule is as follows:

Tembexa Tablets:

Tembexa tablets can be taken on an empty stomach or with a low-fat meal (approximately 400 calories, with approximately 25% of calories from fat). Swallow tablets whole. Do not crush or divide Tembexa tablets.

Tembexa Oral Suspension:

Take Tembexa oral suspension on an empty stomach. Shake oral suspension before use. Use an appropriate oral dosing syringe to correctly measure the total prescribed dose. Discard unused portion after completion of 2 prescribed doses. For patients who cannot swallow, Tembexa oral suspension can be administered by enteral tube (naso-gastric or gastrostomy tubes).

Recommended Dosage for Adults and Pediatrics:

Patient’s Weight (kg)

Tembexa Oral Suspension (10 mg/mL)

Tembexa Tablet (100 mg)

Less than 10 kg

6 mg/kg once weekly for 2 doses (on Days 1 and 8)

N/A

10 kg to less than 48 kg

4 mg/kg once weekly for 2 doses (on Days 1 and 8)

N/A

48 kg and above

200 mg (20 mL) once weekly for 2 doses (on Days 1 and 8)

200 mg (two 100 mg tablets) once weekly for 2 doses (on Days 1 and 8)

Mechanism of Action

Tembexa (brincidofovir) is an antiviral drug against variola (smallpox) virus. Brincidofovir is a lipid conjugate of cidofovir, an acyclic nucleotide analog of deoxycytidine monophosphate. The lipid conjugate is designed to mimic a natural lipid, lysophosphatidylcholine, and thereby use endogenous lipid uptake pathways. Once inside cells, the lipid ester linkage of brincidofovir is cleaved to liberate cidofovir, which is then phosphorylated to produce the active antiviral, cidofovir diphosphate. Based on biochemical and mechanistic studies using recombinant vaccinia virus E9L DNA polymerase, cidofovir diphosphate selectively inhibits orthopoxvirus DNA polymerase-mediated viral DNA synthesis. Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis.

Side Effects

Adverse effects associated with the use of Tembexa may include, but are not limited to, the following:

diarrhea

nausea

vomiting

abdominal pain

The Tembexa drug label comes with the following Black Box Warning: An increased incidence of mortality was seen in Tembexa treated subjects compared to placebo-treated subjects in a 24-week clinical trial when Tembexa was evaluated in another disease.

Clinical Trial Results

The FDA approval of Tembexa was based on efficacy data in two lethal orthopoxvirus animal models of human smallpox disease, the rabbitpox model (New Zealand White rabbits infected with rabbitpox virus) and the mousepox model (BALB/c mice infected with ectromelia virus). In the pivotal studies in each model, Tembexa treatment resulted in statistically significant survival benefit versus placebo following delayed treatment after animals were infected with a lethal viral dose. The FDA’s ‘Animal Rule’ allows for testing of investigational drugs in animal models to support effectiveness in diseases which are not ethical or feasible to study in humans.