Raxibacumab: Monoclonal antibody for inhalational anthrax
No trade name (raxibacumab—GlaxoSmithKline)
GlaxoSmithKline announced the approval of raxibacumab for the treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs, and for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate. Raxibacumab is a monoclonal antibody that works by neutralizing toxins produced by B. anthracis that can cause massive and irreversible tissue injury and death.
Raxibacumab is the first monoclonal antibody approved using the Animal Efficacy Rule, which allows efficacy findings from adequate and well-controlled animal studies to support FDA approval when it is not feasible or ethical to conduct trials in humans. The safety and pharmacokinetic parameters of raxibacumab were evaluated in healthy adult volunteers.
Managing anthrax: New treatment needed
Anthrax is caused by the spore-forming bacterium B. anthracis and can manifest in three forms: cutaneous, gastrointestinal, and inhalational. Of these three types, inhalational anthrax is the most lethal because bacteria can multiply in the lungs and produce toxins before the onset of symptoms. Patients with inhalational anthrax generally manifest with fever, chills, fatigue, and nausea initially. As spores germinate over time, clinical symptoms get progressively worse, with patients experiencing hemorrhagic thoracic lymphadenitis, pleural effusions, and in some cases, hemorrhagic meningitis.
Antibiotics and vaccines have been the cornerstone of treatment for anthrax; however, both treatments have limitations. Antibiotics aid in controlling the infection, but do not clear toxins present in the bloodstream. In addition, some strains may be resistant to antibiotics. Vaccines may be more beneficial in the long term, but do little to treat patients’ acute symptoms. Therefore, another therapeutic option is clearly needed to manage inhalational anthrax.
Animal efficacy rule supports approval
The effectiveness of raxibacumab for inhalational anthrax was demonstrated in one study in monkeys and three studies in rabbits. All animals were administered aerosolized B. anthracis spores, and efficacy was determined by survival at the end of the studies. In the monkey trial, mean time between spore challenge and initiation of study treatment was 42 hours; in two of the rabbit studies, the treatment was initiated at an average of 28 hours postexposure. According to results from these three studies, 64% of animals in the monkey study, 44% of animals in one rabbit study, and 46% of animals in the other rabbit study who received a 40 mg/kg dose of raxibacumab survived exposure to anthrax, compared with none in the placebo groups. All surviving animals developed toxin-neutralizing antibodies.
The final rabbit study assessed the treatment of inhalational anthrax with raxibacumab in combination with levofloxacin compared with the antibiotic alone. Raxibacumab was given as a single dose of 40 mg/kg approximately 84 hours after spore challenge. Data from this study showed that 82% of animals treated with levofloxacin and raxibacumab survived exposure to anthrax, compared with 65% of animals receiving levofloxacin treatment alone.
The safety of raxibacumab was evaluated in three trials in involving 326 healthy adult volunteers. Of these 326 patients, 283 received a single dose, 23 received two doses 14 days apart, and 20 received two doses more than 4 months apart. Rash (2.8%), extremity pain (2.1%), itching (2.1%), and drowsiness (1.5%) were the most common adverse events observed in the safety trials.
Raxibacumab (No trade name)
Drug class: Monoclonal antibody
Indication: Treatment and prevention of inhalational anthrax
Dosage: 40 mg/kg, given I.V. over 2 hours and 15 minutes, for adult patients
- For pediatric patients, the dosing is weight-based, with a dose of 40 mg/kg for those greater than 50 kg, a dose of 60 mg/kg for those greater than 15 kg to 50 kg, and a dose of 80 mg/kg for those who are 15 kg or less
- Diphenhydramine, either oral or I.V., should be given within 1 hour before the raxibacumab infusion to reduce the risk of infusion reactions.
Of note: Infusion-related reactions such as rash, urticaria, and pruritus were reported during administration of the drug. If these reactions occur, the infusion of raxibacumab should be slowed or interrupted and the reaction should be treated appropriately.
Inform patients that the efficacy of raxibacumab was based solely on data from animal models and that only safety studies have been conducted in humans. In addition, educate patients on the most common adverse events that can occur with the infusion, such as rash, itching, and hives.