General Information

Tpoxx (tecovirimat) is an antiviral drug against variola (smallpox) virus.

Tpoxx is specifically indicated for the treatment of human smallpox disease caused by variola virus in adults and pediatric patients weighing at least 13 kg.

Tpoxx is supplied as a capsule for oral administration. The recommended dose is as follows:

Dosage for Adults and Pediatric Patients Weighing at Least 40 kg: 600 mg (three 200 mg capsules) taken twice daily orally for 14 days. Tpoxx should be taken within 30 minutes after a full meal of moderate or high fat.

Dosage for Pediatric Patients: The recommended dosage for pediatric patients is based on weight starting at 13 kg, as seen below. The dose should be given twice daily orally for 14 days and should be taken within 30 minutes after a full meal of moderate or high fat.

Body Weight: 13 kg to less than 25 kg Dose: 200 mg twice daily Number of capsules: contents of one capsule twice daily Drug-Food Preparation: Mix 1 capsule with 30 mL of liquid or soft food.

Body Weight: 25 kg to less than 40 kg Dose: 400 mg twice daily Number of capsules: contents of 2 capsules twice daily Drug-Food Preparation: Mix 2 capsules with 30 mL of liquid or soft food.

Body Weight: 40 kg and above Dose: 600 mg twice daily Number of capsules: contents of 3 capsules twice daily Drug-Food Preparation: Mix 3 capsules with 30 mL of liquid or soft food.

Preparation for administration to pediatrics and those who cannot swallow capsules: capsules can be administered by carefully opening the capsule and mixing the entire contents in 30 mL of liquid (e.g., milk, chocolate milk) or soft food (e.g., apple sauce, yogurt). The entire mixture should be administered within 30 minutes of its preparation.

Clinical Results

FDA Approval

The effectiveness of Tpoxx for treatment of smallpox disease has not been determined in humans because adequate and well-controlled field trials have not been feasible, and inducing smallpox disease in humans to study the drug’s efficacy is not ethical. Therefore, the effectiveness of Tpoxx for treatment of smallpox disease was established based on results of adequate and well-controlled animal efficacy studies of non-human primates and rabbits infected with non-variola orthopoxviruses. Survival rates observed in the animal studies may not be predictive of survival rates in clinical practice.

Efficacy studies were conducted in cynomolgus macaques infected with monkeypox virus, and New Zealand white (NZW) rabbits infected with rabbitpox virus. The primary efficacy endpoint for these studies was survival. In non-human primate studies, cynomolgus macaques were lethally challenged intravenously with 5 x 107 plaque-forming units of monkeypox virus; tecovirimat was administered orally once daily at a dose level of 10 mg/kg for 14 days, starting at Day 4, 5 or 6 post-challenge. In rabbit studies, NZW rabbits were lethally challenged intradermally with 1,000 plaque-forming units of rabbitpox virus; tecovirimat was administered orally once daily for 14 days at a dose level of 40 mg/kg, starting at Day 4 post-challenge. The timing of tecovirimat dosing in these studies was intended to assess efficacy when treatment is initiated after animals have developed clinical signs of disease, specifically dermal pox lesions in cynomolgus macaques, and fever in rabbits. Clinical signs of disease were evident in some animals at Day 2-3 post-challenge but were evident in all animals by Day 4 post-challenge. Survival was monitored for 3-6 times the mean time to death for untreated animals in each model. Treatment with tecovirimat for 14 days resulted in statistically significant improvement in survival relative to placebo, except when given to cynomolgus macaques starting at Day 6 post-challenge.

Mechanism of Action

Tpoxx (tecovirimat) targets and inhibits the activity of the orthopoxvirus VP37 protein (encoded by and highly conserved in all members of the orthopoxvirus genus) and blocks its interaction with cellular Rab9 GTPase and TIP47, which prevents the formation of egress-competent enveloped virions necessary for cell-to-cell and long-range dissemination of virus.