Vaccines:

Indications for: BIOTHRAX

Pre-exposure prophylaxis of disease caused by Bacillus anthracis in high risk persons due to occupation or other activities for anthrax disease. Post-exposure prophylaxis after suspected or confirmed Bacillus anthracis exposure, when given with recommended antibacterial drugs.

Clinical Trials:

Pre-Exposure Prophylaxis

Controlled Field Study

  • A controlled field study using an earlier version of a protective antigen-based anthrax vaccine developed in the 1950’s and supplied by G. G. Wright and associates of the U.S. Army Chemical Corps, Fort Detrick, Frederick, MD, that consisted of an aluminum potassium sulfate-precipitated cell-free filtrate from an aerobic culture, was conducted from 1955-1959.

  • During the study, there were 26 cases reported across 4 mills in the northeastern US (5 inhalation and 21 cutaneous).

  • Of the 21 cutaneous cases, 15 were in the placebo arm, 3 were in the observational arm, and 3 received anthrax vaccine.

  • The calculated efficacy of the vaccine to prevent all types of anthrax disease was 92.5% regardless of the route of exposure or clinical manifestations.

BioThrax

  • Between 1962 and 1974, individuals received either BioThrax or the earlier protective antigen-based anthrax vaccine used in the field study described above.

  • Of the 27 reported cases of anthrax, 24 cases occurred in unvaccinated individuals.

  • In vaccinated individuals 1 case occurred after the person had been given 1 dose of anthrax vaccine and 2 cases occurred after individuals had been given 2 doses of anthrax vaccine. 

  • There were no documented cases of anthrax for individuals who received at least 3 doses of the originally licensed 6-dose series of anthrax vaccine.

Prospective Study

  • Between 2002 and 2007, a prospective double-blinded, randomized, placebo-controlled and active-controlled study was conducted to evaluate the impact on safety and immunogenicity on changing the administration route from SC to IM, and reducing the number of doses. This study included 1564 healthy men and women 18 to 61 years of age. Patients were randomly assigned to 1 of 6 groups (see full labeling). 

  • Immunoglobulin G (IgG) antibodies directed against anthrax protective antigen (PA) were measured using ELISA at the Week 8 and Months 7, 13, 19, 31, and 43 time points. The 3 primary immunogenicity endpoints were: (1) Geometric Mean Concentraion (GMC) (mcg/mL), (2) Geometric Mean Titer (GMT), and (3) percentage with 4-fold rise in anti-PA antibody titer from baseline.

  • To compare the originally licensed 6-dose SC schedule (0, 2, 4 weeks and 6, 12, and 18 months) versus a 3-dose IM primary series (at 0, 1, and 6 months), non-inferiority analyses were performed for all three primary immunogenicity endpoints.

  • Noninferiority was shown for all analyses supporting a 3 dose primary series of BioThorax administered IM at 0, 1, and 6 months followed by booster doses at 12 and 18 months and at 1-year intervals to maintain protective immunity.

  • Noninferiority was also shown supporting a 4 dose SC primary series of BioThorax administered at Weeks 0, 2, 4, and at 6 months followed by booster doses at 12 and 18 months after initiation, and at 1-year intervals to maintain protective immunity.

 

Post-Exposure Prophylaxis

  • A clinical study evaluated the post-exposure SC administration schedule of BioThorax in healthy adults following 3 doses at 0, 2, and 4 weeks. The primary immunogenicity endpoint was the proportion of subjects achieving a threshold TNA NF50 value ≥0.56 at Day 63, 5 weeks after the third vaccination. 

  • 71.2% of patients achieved NF50 value ≥0.56 at Day 63 and the lower bound of the 95% CI was 64.1%.

  • In a separate analysis of this clinical study using the threshold associated with a 70% probability of survival in nonhuman primates (NHP), 93.5% of patients achieved NF50 value ≥0.29 at Day 63. The lower bound of the 95% CI was 88.9%.

 

Non-Interference of Post-Exposure Prophylaxis Vaccination and Antimicrobials When Used Concurrently

  • In an open-label study, the potential impact of 0.5mL of BioThorax administered SC at 0, 2, and 4 weeks was evaluated on the pharmacokinetics of ciprofloxacin in 154 healthy adult male and female patients. The potential impact of ciprofloxacin was also evaluated on the immunogenicity of BioThorax 2 weeks after the last BioThorax dose.

  • Concomitant use of BioThorax SC with oral ciprofloxacin did not alter the pharmacokinetics of ciprofloxacin, and vice versa.

Adult Dosage:

For IM inj (into the deltoid) or SC inj (over the deltoid) only. Each dose is 0.5mL. 18–65yrs (Pre-exposure): give as IM inj at 0, 1, and 6 months with booster doses at 6 and 12 months after completion of primary series, then at 12-month intervals thereafter; if at risk of hematoma: may give as SC inj at 0, 2, 4 weeks, and 6 months with booster doses at 6 and 12 months after completion of primary series, then at 12-month intervals thereafter; (Post-exposure): give as SC inj at 0, 2, and 4 weeks post-exposure in combination with antimicrobial therapy.

Children Dosage:

Not established.

BIOTHRAX Contraindications:

Severe allergic reaction after a previous BioThrax dose.

BIOTHRAX Warnings/Precautions:

Vaccination may not protect all individuals. Have medical treatment and supervision available to manage anaphylactic reactions. History of anthrax disease. Latex allergy. Immunocompromised. Elderly (>65yrs): not indicated. Pregnancy (Cat.D): not recommended. Nursing mothers.

BIOTHRAX Classification:

Anthrax vaccine.

BIOTHRAX Interactions:

Concomitant other vaccines: inject at different sites. Concomitant immunosuppressants, chemotherapy, high-dose corticosteroids (>2 weeks), radiation therapy: may get sub-optimal response.

Adverse Reactions:

Tenderness, pain, erythema, edema, limited arm motion, muscle aches, fatigue, headache; allergic reactions.

Note:

Register pregnant patients in the Vaccine pregnancy registry by calling (619) 553-9255.

Generic Drug Availability:

NO

How Supplied:

Multi-dose vials (5mL)—1