With an eye to preparing for potential threats, the FDA has granted approval for the first live, non-replicating vaccine to prevent smallpox and monkeypox. Developed by Bavarian Nordic A/S and branded as Jynneos, after a priority review it was approved for prevention of the diseases in adults determined to be at high risk for the viral infections.

Jynneos, also known as MVA-BN (modified vaccinia Ankara), is already approved in the EU, where it is marketed as Imvanex for active immunization against smallpox, and in Canada where it is sold as Imvamune, also for smallpox alone. In the U.S., it will be made available for those determined to be at high risk of either smallpox or monkeypox infection, the FDA said. It is also being included in the Strategic National Stockpile, which has already taken delivery of 28 million doses of liquid-frozen MVA-BN and will continue to see its supply replenished under an ongoing 10-year contract with the company. It wasn't immediately clear how much individual doses would cost or under what non-emergency circumstances they might be made available.

Alongside the approval, the FDA granted Bavarian Nordic a priority review voucher under the Material Threat Medical Countermeasure PRV program that can be used to accelerate FDA review of a future human drug application. The Copenhagen-based company intends to sell the voucher, it said.

Jynneos is administered as a subcutaneous injection (0.5 mL) based on a live, attenuated vaccinia virus incapable of replicating in the body, yet still capable of eliciting a potent immune response, according to the company. It was developed in partnership with the U.S. government to ensure a wide variety of individuals could benefit from protection, including those with weakened immune systems or who are at high risk of adverse reactions to traditional smallpox vaccines, which are based on replicating vaccinia virus strains.

The vaccine was approved for smallpox based on the results of studies in more than 7,800 adults who received at least one dose in 22 clinical trials, including two phase III studies. The phase III trials demonstrated noninferiority in terms of immunogenicity measured by a plaque reduction neutralization test of Jynneos vs. Emergent Biosolutions Inc.'s ACAM-2000, the other U.S.-licensed, replication-competent smallpox vaccine already stockpiled in the U.S.

The approval for monkeypox is based on survival data obtained in lethal monkeypox virus challenge studies in nonhuman primates. Overall survival in various models ranged from 80% to 100% of Jynneos-vaccinated animals compared to 0% to 40% in control animals.

After routine vaccinations for smallpox in the U.S. were stopped in 1972, naturally occurring smallpox disease was certified as eradicated in America in 1980. Today, most people in the U.S. and abroad have no immunity. "Therefore, although naturally occurring smallpox disease is no longer a global threat, the intentional release of this highly contagious virus could have a devastating effect," said Peter Marks, director of the FDA's Center for Biologics Evaluation and Research. "Today's approval reflects the U.S. government's commitment to preparedness through support for the development of safe and effective vaccines, therapeutics and other medical countermeasures," he said.

Monkeypox does not occur naturally in the U.S., though in 2003 the country experienced an outbreak of the virus, which was the first time human monkeypox was reported outside of Africa.

The most common adverse reactions associated with Jynneos were injection site reactions and systemic adverse reactions such as muscle pain, headache, fatigue, nausea, myalgia and chills. Serious adverse reactions were reported in 0.05% of subjects who received Jynneos and included Crohn's disease, sarcoidosis, extraocular muscle paresis and throat tightness. Cardiac adverse reactions occurred in 0.08% of clinical trial participants.

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