FDA approves vaccine for use after known or suspected anthrax exposure.

November 23, 2015

The U.S. Food and Drug Administration approved a new indication for BioThrax (Anthrax Vaccine Adsorbed) to prevent disease following suspected or confirmed exposure to Bacillus anthracis, the bacterium that causes anthrax disease. The vaccine’s new use is approved for people 18 through 65 years of age in conjunction with recommended antibiotic treatment. BioThrax was initially approved by the FDA in 1970 for the prevention of anthrax disease in persons at high risk of exposure.

Anthrax disease, especially the inhalation form, is often fatal if not promptly treated. Anthrax is considered one of the more likely agents to be used in a biological attack, primarily because its spores are very stable and easy to disperse. Although it is rare, people may contract anthrax disease through natural exposures, such as contact with infected animals or contaminated animal products.

BioThrax is the first vaccine to receive approval based on the Animal Rule. The Animal Rule allows animal efficacy data to be used as a basis for approval when human efficacy studies are not ethical or feasible.

DESCRIPTION

BioThrax(Anthrax Vaccine Adsorbed) is a sterile, milky-white suspension for intramuscular or subcutaneous injections made from cell-free filtrates of microaerophilic cultures of an avirulent, nonencapsulated strain of Bacillus anthracis.

The production cultures are grown in a chemically defined protein-free medium consisting of a mixture of amino acids, vitamins, inorganic salts, and sugars. The final product, prepared from the sterile filtrate culture fluid contains proteins, including the 83kDa protective antigen (PA) protein, released during the growth period and contains no dead or live bacteria. The final product is formulated to contain 1.2 mg/mL aluminum, added as aluminum hydroxide in 0.85% sodium chloride. The final product is formulated to contain 25 mcg/mL benzethonium chloride and 100 mcg/mL formaldehyde, added as preservatives.

CLINICAL PHARMACOLOGY

Mechanism of Action

Anthrax is a zoonotic disease caused by the Gram-positive, spore-forming bacterium Bacillus anthracis. Although an immune correlate of protection is unknown, BioThrax induces antibodies raised against PA, which may contribute to protection by neutralizing the activities of the cytotoxic lethal toxin and edema toxin of Bacillus anthracis. 3 Bacillus anthracis proteins other than PA may be present in BioThrax, but their contribution to protection has not been determined.

DOSAGE AND ADMINISTRATION

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Each dose is 0.5 mL:

Primary series: Intramuscular injections at 0, 1, and 6 months

Booster doses: Intramuscular injections at 12 and 18 months after initiation of the primary series, and at 1-year intervals thereafter.

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BioThrax may be administered by the subcutaneous route (for example, in persons who are at risk for hematoma formation following intramuscular injection).

The schedule for BioThrax administered subcutaneously is 0, 2, 4 weeks, and 6 months with booster doses at 12 and 18 months, and at 1 year intervals thereafter.

DOSAGE FORMS AND STRENGTHS

Suspension for injection (0.5 mL dose) in 5 mL multidose vials.

Safety & Efficacy

Protective antibody levels, which were determined in rabbit and monkey studies, were used to predict efficacy in humans based on an assessment of the extent of antibody response achieved in human study participants. A 70 percent probability of survival in animal models from inhalational anthrax disease was deemed a reasonable level of protection and likely to provide reasonable benefit in humans.

The ability of BioThrax to increase the probability of survival after stopping post-exposure antibiotic treatment was assessed in rabbits. Rabbits treated with both antibiotics and BioThrax had a survival rate of 70 to 100 percent, depending on the vaccine dose administered. In contrast, in two studies of rabbits that received only antibiotic treatment, survival rates were 44 and 23 percent respectively.

The safety and antibody responses to BioThrax in humans were evaluated in a multi-center study conducted in the United States. Subcutaneous (under the skin) injections were given to 200 healthy adults in three doses at zero, two, and four weeks. The majority of study participants generated antibody responses that correlated to a 70 percent probability of survival that was observed in animal models.

 

CONTRAINDICATIONS

Severe allergic reaction (e.g. anaphylaxis) after a previous dose of BioThrax or a component of the vaccine.

WARNINGS AND PRECAUTIONS

The stopper of the vial contains dry natural rubber and may cause allergic reactions to patients with a possible history of latex sensitivity.

Pregnancy: Avoid use in pregnancy unless the potential benefit outweighs the potential risk to the fetus

ADVERSE REACTIONS

Local (injection-site) adverse reactions(>10%) – The most common  observed in clinical studies were tenderness, pain, erythema, edema, and arm motion limitation.

Systemic adverse reactions(≥5%)- The most common were muscle aches, fatigue, and headache.

HOW SUPPLIED/STORAGE AND HANDLING

BioThrax is supplied in 5 mL multidose vials containing ten 0.5 mL doses. NDC 64678-211-05 (vial), 64678-211-01 (carton) Store at 2 °C to 8 °C (36 °F to 46 °F). Do not freeze. Do not use BioThrax after the expiration date printed on the label.

BioThrax is manufactured by Emergent BioDefense Operations Lansing LLC, based in Lansing, Michigan.

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