A Comparative Pharmacokinetic Study to Evaluate the Bioequivalence and Safety of A Humanized Recombinant Monoclonal Antibody Targeting Human Epidermal Growth Factor Receptor 2 (HER2) with the Reference Herceptin in Healthy Chinese Subjects

Purpose:This study aimed to evaluate the safety, tolerability, pharmacokinetics and bioequivalence of a test humanized recombinant monoclonal antibody targeting Human Epidermal Growth Factor receptor 2 (HER-2) with the reference Herceptin®.Materials and methods:The trial consists of two parts (part I and part II). Part I was an open-label, sequential-cohort dose-escalation study, QLHER2 (test) was intravenous infusion at single doses escalating from 0.2 to 6 mg/kg (0.2, 1, 2, 4 and 6mg/kg) and Herceptin(reference) 4 mg/kg in 16 healthy subjects, to evaluated the safety, tolerability and pharmacokinetics of QLHER2. Part II was a randomized, double-blind, parallel-group study to evaluate the bioequivalence of QLHER2 and Herceptin in 60 subjects.Results:Following a 1.5-h intravenous infusion of single ascending doses of QLHER2 (1, 2, 4, or 6 mg/kg) In part I, Cmax and Tmax were 19.43-120.01 μg/mL and 68.91-157.87 h, respectively. AUC0-t and CL were 1.91-34.21 h*μg/mL and 0.54-0.12 ml/h/kg, indicating decreased clearance at higher doses, with a greater than proportional increase in the AUC0-t , and the t1/2 was 68.91-157.87 h. In part II, Plasma concentrations appeared to be comparable between QLHER2 and Herceptin over the 70-day sampling period and the QLHER2/Herceptin ratio of the Cmax and AUC0-t was 105.90% (90% CI: 95.69-117.26) and 95.79% (90% CI: 87.74-106.40%), respectively.Conclusion:The 90% CIs of the Cmax and AUC0-t for QLHER2/Herceptin ratio were within the range of 80.0-125.00% indicated that QLHER2 was bioequivalent to Herceptin. The results supported for further evaluation of QLHER2.Trial registration number: ChiCTR2000041577 and ChiCTR2100041802Date of registration: December 30,2020 and January 5, 2021

Management of Refractory Gastrointestinal Bleeding in Hereditary Hemorrhagic Telangiectasia with Bevacizumab

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder resulting in vascular malformations of several organs including the pulmonary, cerebral, and gastrointestinal systems. One sequela is recurrent gastrointestinal (GI) bleeding. Bevacizumab (Bev) is emerging as an effective treatment of recurrent gastrointestinal bleeding in HHT. Bev is a recombinant monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), an integral part of angiogenesis.

Upper gastrointestinal tract lymphoma with Natalizumab: Evidence of impaired immune surveillance?

The humanised recombinant monoclonal antibody natalizumab (Tysabri), is a selective antagonist of the α4 subunit of the leukocyte adhesion molecule integrin, VLA-3. Blockade of VLA-3 leads to inhibition of immune cell transmigration into target organs, notably the intestinal lining and central nervous system.1,2 Natalizumab is approved to treat relapsing-remitting Multiple Sclerosis (RRMS) in the US and Europe, and Crohn’s Disease in the US. Following approval in 2004, natalizumab was withdrawn in 2005 due to 3 reported cases of progressive multifocal leukoencephalopathy (PML). In 2006, it re-entered the market with additional monitoring requirements.

Experience of using dupilumab in the treatment of severe asthma

The article provides data on modern approaches to the treatment of patients with severe uncontrolled bronchial asthma with an emphasis on the use of dupilumab, a human recombinant monoclonal antibody to the alpha subunit of the interleukin (IL)-4 receptor, which inhibits signal transmission from both IL-4 and IL-13. The results of dupilumab pivotal randomized clinical trials DRI12544, QUEST and VENTURE are summarized. Indications for use of this medicinal product are listed in Federal Clinical Guidelines on the management of asthma (year of revision 2019). Clinical cases with various clinical course of bronchial asthma are described, including cases with frequent exacerbations. In conclusion, dupilumab could be a treatment of choice for the patients with severe bronchial asthma and it is reasonable from an economic, clinical and pathogenetic point of view.