Related Experiment Video
Updated: Jun 30, 2025
Bronchial Thermoplasty: A Novel Therapeutic Approach to Severe Asthma
Published on: November 4, 2010
Benralizumab in children with severe eosinophilic asthma: Pharmacokinetics and long-term safety (TATE study)
H James Wedner1, Takao Fujisawa2, Theresa W Guilbert3,4
1Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Insights
Benralizumab treatment in children with severe eosinophilic asthma showed favorable pharmacokinetics, pharmacodynamics, and safety profiles. These findings support its use in younger patients, similar to adolescents and adults.
Area of Science:
- Pharmacology and Therapeutics
- Pediatric Asthma Management
- Immunology
Background:
- Benralizumab is an approved add-on treatment for severe uncontrolled asthma.
- Previous studies focused on patients aged 12 years and older.
- The TATE study investigated benralizumab in children.
Purpose of the Study:
- To evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of benralizumab in children.
- To assess benralizumab's efficacy in severe eosinophilic asthma in a pediatric population.
Main Methods:
- Open-label, Phase 3 study (TATE) in children aged 6-11 years (and 12-14 from Japan).
- Benralizumab administered at 10/30 mg based on weight (<35/≥35 kg).
- Primary endpoints included Cmax, clearance, t1/2, and blood eosinophil counts; safety and tolerability were assessed.
Main Results:
- Near-complete depletion of blood eosinophils observed across all dose/weight groups.
- Pharmacokinetic parameters (clearance, t1/2) were consistent with expected profiles.
- Exploratory analyses indicated numerical improvements in lung function and asthma control.
Conclusions:
- Pharmacokinetic, pharmacodynamic, and safety data support benralizumab's long-term use in children with severe eosinophilic asthma.
- Findings were comparable to those in adolescent and adult populations.
- Benralizumab demonstrates a favorable profile for pediatric severe eosinophilic asthma treatment.
Background:
Benralizumab is an anti-interleukin-5 receptor α monoclonal antibody approved as an add-on maintenance treatment for patients with uncontrolled severe asthma. Prior Phase 3 studies have evaluated benralizumab in patients aged ≥12 years with severe uncontrolled asthma. The TATE study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of benralizumab treatment in children.
Methods:
TATE was an open-label, Phase 3 study of benralizumab in children aged 6-11 years from the United States and Japan (plus participants aged 12-14 years from Japan) with severe eosinophilic asthma. Participants received benralizumab 10/30 mg according to weight (<35/≥35 kg). Primary endpoints included maximum serum concentration (Cmax ), clearance, half-life (t1/2 ), and blood eosinophil count. Clearance and t1/2 were derived from a population PK (popPK) analysis. Safety and tolerability were also assessed.
Results:
Twenty-eight children aged 6-11 years were included, with an additional two participants from Japan aged 12-14 years also included in the popPK analysis. Mean Cmax was 1901.2 and 3118.7 ng/mL in the 10 mg/<35 kg and 30 mg/≥35 kg groups, respectively. Clearance was 0.257, and mean t1/2 was 14.5 days. Near-complete depletion of blood eosinophils was shown across dose/weight groups. Exploratory efficacy analyses found numerical improvements in mean FEV1 , mean ACQ-IA, patient/clinician global impression of change, and exacerbation rates. Adverse events occurred in 22/28 (78.6%) of participants; none led to discontinuation/death.
Conclusion:
PK, PD, and safety data support long-term benralizumab in children with severe eosinophilic asthma, and were similar to findings in adolescents and adults.
Trial Registration:
ClinicalTrials.gov-ID: NCT04305405.
Related Concept Videos
01:19Antiasthma Drugs: Leukotriene Modifiers
Leukotriene modifiers work through two distinct mechanisms:
01:25Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
01:25Antiasthma Drugs: β2-Adrenoceptor Agonists
One class of bronchodilators includes β2-adrenoceptor agonists. These agents target the β2-adrenoceptors located on bronchial smooth muscle cells. By stimulating these receptors, β2-agonists induce...
01:23Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
01:26Asthma-II: Pathophysiology and Classification
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
01:24Antiasthma Drugs: Methylxanthines
Theophylline is thought to inhibit phosphodiesterase enzymes, increasing intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). This rise in cAMP and cGMP concentrations stimulates cardiac function,...