Comparison of autoinjector with accessorized prefilled syringe for benralizumab pharmacokinetic exposure: AMES trial results

Abstract

Objective: We compared the pharmacokinetic exposure following a single subcutaneous dose of benralizumab 30 mg using either autoinjectors (AI) or accessorized prefilled syringes (APFS). APFS and AI functionality and reliability for at-home benralizumab delivery have been demonstrated in the GREGALE and GRECO studies, respectively. Methods: In the open-label AMES study (NCT02968914), 180 healthy adult men and women were randomized to one of two device (AI or APFS) and three injection site (upper arm, abdomen, or thigh) combinations. Randomization was stratified by weight (<70 kg, 70-84.9 kg, and !85 kg). Blood eosinophil counts were measured on Days 1, 8, 29, and 57. Results: Benralizumab pharmacokinetic exposure was similar between AI and APFS. Geometric mean ratios (AI/APFS) (90% CI) were 92.8% (87.4-98.6) and 94.5% (88.2-101.2) for two area under the concentration-time curve measurements (AUC last and AUC inf). Benralizumab exposure was approximately 15-30% greater for thigh vs. abdomen or upper arm administration. Exposure was slightly greater for APFS vs. AI regardless of injection site or weight class. These differences were unlikely to be clinically relevant, as eosinophil depletion was achieved consistently with both devices at all injection sites. No device malfunctions were reported. No new or unexpected safety findings were observed. Conclusion: Benralizumab pharmacokinetic exposure was similar between AI and APFS, with consistent blood eosinophil count depletion observed with both devices. These results support benralizumab administration with either AI or APFS, providing patients and physicians increased choice, flexibility, and convenience for potential at-home delivery.

<p>Single-Use Autoinjector Functionality And Reliability For At-Home Administration Of Benralizumab For Patients With Severe Asthma: GRECO Trial Results</p>

“…The mean 1-point improvement in ACQ-6 score during this 28-week study is within the range of improvements observed over 1 year in the SIROCCO and CALIMA studies and over 20 weeks in GREGALE, and indicates clinically important improvement 6,9,14. Furthermore, a nearly complete depletion of blood eosinophils after benralizumab 30-mg injection was observed in GRECO, similar to results in the GREGALE trial and in AMES, a pharmacokinetic study of single-dose benralizumab administration in a clinical setting 6,8,9,14,15. Pharmacokinetics of benralizumab administered via AI were stable during treatment, similar to that observed with APFS in the GREGALE study 14.…”

“…The incidence of AEs related to injection site in GRECO (6.6% of patients) was numerically greater than that observed in the 12-week BISE and 28-week ZONDA studies (up to 3% of patients), 28-week GREGALE study (4% of patients), and 1-year SIROCCO and CALIMA studies (both 2%) 8,14,17. In AMES, incidence of injection-site reactions was even smaller (1% for AI, none reported for APFS) 15…”

“…Efficacy, pharmacokinetic, and pharmacodynamic assessments confirmed that benralizumab exposure following at-home use of APFS was comparable to exposure following administration by health care professionals at clinical sites 14. A further study of benralizumab with healthy volunteers demonstrated that pharmacokinetics following a single injection were similar between APFS and AI 15…”

Targeting IL‐5 pathway against airway hyperresponsiveness: A comparison between benralizumab and mepolizumab

“…Such a condition can be translated to asthmatic patients before the next dose administration of a monoclonal antibody. Accordingly with pharmacokinetic studies in healthy subjects (Martin et al, 2019;Shabbir et al, 2019) that received approved doses of monoclonal antibodies (European Medicines Agency, 2015US Food andDrug Administration, 2015, 2017), while the maximum plasma concentrations of benralizumab and mepolizumab were '3 and '12 μg/ml −1 , respectively, the trough concentrations were '1 and '5 μg/ml −1 , respectively. Indeed, our results indicate that at these concentrations both the agents are effective in submaximally inhibiting the airway hyperresponsiveness to histamine in isolated airways.…”

Targeting IL-5 pathway against airway hyperresponsiveness: a challenge between benralizumab and mepolizumab

“…Such a condition can be translated to asthmatic patients before the next dose administration of a mAb. Accordingly with pharmacokinetic (PK) studies in healthy subjects (Martin et al, 2019;Shabbir et al, 2019) that received approved doses of mAbs (European Medicines Agency, 2015; European Medicines Agency, 2018; US Food and Drug Administration, 2015; US Food and Drug Administration, 2017), while the maximum plasma concentrations of benralizumab and mepolizumab were [? ]3 μg/ml and [?…”