The FDA today approved the first drug indicated for smallpox, SIGA Technologies’ TPOXX® (tecovirimat), which was developed with the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA).

TPOXX is a small molecule antiviral therapy designed to mitigate the impact of a potential outbreak of smallpox. While the disease was declared to have been eradicated by the World Health Organization in 1980, the U.S. and other nations have prioritized development of medical countermeasures against bioweapons in the years since September 11, 2001, when al-Qaeda terrorists mass-murdered 2,977 people on American soil.

“To address the risk of bioterrorism, Congress has taken steps to enable the development and approval of countermeasures to thwart pathogens that could be employed as weapons. Today’s approval provides an important milestone in these efforts,” FDA Commissioner Scott Gottlieb, M.D., said in a statement issued by the agency. “This new treatment affords us an additional option should smallpox ever be used as a bioweapon.”

The FDA based its approval on data from 12 clinical trials of oral TPOXX in more than 700 healthy human volunteers. The trials showed no drug-related serious adverse events, SIGA said.

Four pivotal trials in non-human primates (NHPs) and two pivotal trials in rabbits demonstrated that TPOXX significantly reduced both mortality and viral load in NHP infected with monkeypox virus, and in rabbits infected with rabbitpox virus. The results of these studies were published in the July 5, 2018 issue of the New England Journal of Medicine.

The safety of TPOXX was evaluated in 359 healthy human volunteers without a smallpox infection. The most frequently reported side effects were headache, nausea, and abdominal pain, according to the FDA.

”TPOXX is proof that public-private partnerships work when the partners are committed to a focused mission,” SIGA CEO Phil Gomez, Ph.D., added in a company statement. “The approval validates this novel smallpox therapy as an important medical countermeasure in response to a potential smallpox outbreak.”

$472M BARDA Contract

With the approval, SIGA said, it is entitled to a $41 million hold-back payment under its a $472 million procurement and development contract with BARDA, provided that BARDA confirms that there is no difference between TPOXX and the courses of the treatment that have already been delivered to the Strategic National Stockpile (SNS).

TPOXX will be available initially only through the SNS. Under its contract with BARDA, SIGA has delivered 2 million courses of oral TPOXX to the SNS. A Request for Proposal has been issued for the maintenance of a smallpox antiviral stockpile within the SNS.

SIGA said it intends to explore additional markets and potential indications for TPOXX in the U.S. and worldwide. 

Concurrent with the approval, the FDA granted SIGA’s request for a Material Threat Medical Countermeasure Priority Review Voucher (PRV) that can be used for obtaining accelerated review of a future SIGA product, or sold to a third party. The PRV is the first to be awarded under the Material Threat Countermeasure PRV program created through the 2016 21st Century Cures Act. 

The FDA also approved a seven-year expiry for TPOXX. Based on that extended shelf-life determination, SIGA said, it will ask BARDA to exercise an option for a $50 million payment to the company. The exercise of the option is at BARDA’s sole discretion.

The FDA gave its approval to TPOXX about a month ahead of its Prescription Drug User Fee Act (PDUFA) target decision date of August 8—and more than two months after the FDA’s Antimicrobial Drugs Advisory Committee voted unanimously (17-0) to recommend approval, finding that that the benefits of TPOXX outweighed its risks.

During the May 1, 2018 FDA Advisory committee meeting, several members suggested that SIGA explore additional indications, including prophylactic use in individuals exposed to smallpox and other orthopoxviruses, such as monkeypox, which also infects humans.

“SIGA will examine these potential markets and the feasibility of expanding the TPOXX label to include these indications,” the company stated.

TPOXX received the FDA’s Fast Track and Priority Review designations, as well as the agency’s Orphan Drug designation.

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