The aptamer BC 007 completely neutralizes agonistic autoantibodies directed against β1-adrenoceptors:

• DOI: 10.18416/rab.2018.1809023
• Publication Date: 2018-09-28
• Authors: Niels‐Peter Becker; Johannes Mueller; Annekathrin Haber...; Katrin Wenzel; Gerd Wallukat; Peter Goettel; Sarah Schulze Rothe; Ingolf Schimke; Georg Golor; Matthias Großmann; Angela Sinn; Martina Steiper; Tuba Yılmaz; Anne Wallukat; Hanna Davideit; Susanne Becker
• Keywords: Tolerability; Immunoadsorption; Dose

Background: 80 percent of patients with non-ischemic heart failure (HF) and reduced ejection fraction have autoantibodies against β1- adrenoceptors (β1-AAB), which cause and/or sustain HF. The removal β1-AAB by immunoadsorption (IA) leads to an improvement cardiac function significantly mortality. With the aptamer BC 007, a new drug is under study that neutralizes G-Protein-coupled receptors (GP-AAB) including β1-AAB. Aptamers are often referred as chemical antibodies offer number advantages over e.g. peptides biologics when used for treatment. Based on in vitro studies followed animal testing, 007 was recently step-by-step transferred humans. We present here Phase I investigated safety, tolerability, pharmacological effect 007.Methods: In randomized, double blind, placebo controlled single ascending dose study, 3 cohorts 8 male healthy subjects each (age 18 - 45 yrs) were dosed 15, 50 150 mg i. v. infusion 20 min. Additional elderly both sexes (55 70 received BC007 or placebo. Subsequently, open labelled part 5 6 volunteers 75 yrs), who showed evidence GP-AAB dosages 50, 150, 300, 450, 750 tested. Infusion duration min 40 450 cohort. Subjects safety carefully monitored during (ECG, blood pressure, lab, injection site reactions, VS, physical examination, adverse events). 12 samples taken from before began until 24 h thereafter clinical chemistry, hematological pharmacokinetic analysis. Urine collected.Results: extremely well tolerated without clinically relevant events. neutralization has been seen after 1 individuals cohort, 2/6 300 400 5/6 A slightly elevated aPTT (max 49 s) observed cohort quickly normalized end infusion. AUC increased rising dosage 21 556 μg*min/mL, Cmax 1610 15832 ng/mL. half-life short at appr 4 min.Conclusion: powerful favorable side-effect profile will be tested first causative acting induced failure. Derived IA data, huge HF profit this drug.