ATC Group: B06A Other hematological agents

Berotralstat is an inhibitor of plasma kallikrein. In patients with hereditary angioedema (HAE) due to C1-INH deficiency or dysfunction, normal regulation of plasma kallikrein activity is impaired, which leads to uncontrolled increases in plasma kallikrein activity and bradykinin release, resulting in HAE attacks consisting of swelling (angioedema).

Betibeglogene autotemcel adds functional copies of a modified β-globin gene into the patients' HSCs through transduction of autologous CD34+ cells with BB305 LVV, thereby addressing the underlying genetic cause of the disease. After betibeglogene autotemcel infusion, transduced CD34+ HSCs engraft in the bone marrow and differentiate to produce RBCs containing biologically active β^A-T87Q-globin (a modified β-globin protein) that will combine with α-globin to produce functional Hb containing β^A-T87Q-globin (HbA^T87Q).

C1 inhibitor is a single chain glycoprotein found in plasma and a member of the serine protease inhibitor, or serpin, superfamily of proteins. C1 inhibitor inhibits the complement system by binding C1r and C1s and is the most important inhibitor of contact activation, regulating the contact system and the intrinsic coagulation pathway by binding to and inactivating kallikrein and factor XIIa.

Conestat alfa, a recombinant human complement component 1 (C1) esterase inhibitor (rhC1-INH), is an analogue of human C1-INH and is obtained from the milk of rabbits expressing the gene coding for human C1-INH. C1-INH exerts an inhibitory effect on several proteases (target proteases) of the contact and complement systems.

Crizanlizumab-tmca is a humanized IgG2 kappa monoclonal antibody that binds to P-selectin and blocks interactions with its ligands including P-selectin glycoprotein ligand 1.

Ecallantide is a potent (Ki=25 pM), selective, reversible inhibitor of plasma kallikrein. Ecallantide binds to plasma kallikrein and blocks its binding site, inhibiting the conversion of HMW kininogen to bradykinin.

Exagamglogene autotemcel is a cell therapy consisting of autologous CD34+ HSPCs ex vivo edited by CRISPR/Cas9-technology. The highly specific guide RNA enables CRISPR/Cas9 to make a precise DNA double-strand break at the critical transcription factor binding site (GATA1) in the erythroid specific enhancer region of the BCL11A gene. As a result of the editing, GATA1 binding is irreversibly disrupted and BCL11A expression reduced. Reduced BCL11A expression results in an increase in γ-globin expression and foetal haemoglobin (HbF) protein production in erythroid cells, addressing the absent globin in transfusion-dependent β-thalassemia (TDT) and the aberrant globin in sickle cell disease (SCD), which are the underlying causes of disease.

Hemin arginate is indicated for hepatic porphyria (intermittent acute porphyria, porphyria variegata and hereditary coproporphyria). Hemin, by contributing to the re-establishment of normal levels of haemoproteins and of respiratory pigments, corrects the biological disorders observed in patients with porphyria.

Hyaluronidase is an enzyme that has a temporary and reversible depolymerising effect on the polysaccharide hyaluronic acid, which is present in the intercellular matrix of connective tissue.

Icatibant is a selective competitive antagonist at the bradykinin type 2 (B2) receptor. It is a synthetic decapeptide with a structure similar to bradykinin, but with 5 non-proteinogenic amino acids. In HAE increased bradykinin concentrations are the key mediator in the development of the clinical symptoms.

Lanadelumab is a fully human, monoclonal antibody (IgG1/κ-light chain). Lanadelumab inhibits active plasma kallikrein proteolytic activity. Lanadelumab provides sustained control of plasma kallikrein activity and thereby limits bradykinin generation in patients with HAE.