{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:29:16Z","timestamp":1791116956939,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"s4","license":[{"start":{"date-parts":[[2014,4,25]],"date-time":"2014-04-25T00:00:00Z","timestamp":1398384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The primary major issue in haemophilia treatment remains the development of inhibitors. Recently two novel bypassing products have been developed. First, a humanized bispecific antibody against FIXa and FX, termed <jats:styled-content style=\"fixed-case\">hBS<\/jats:styled-content>23, was produced utilizing these two molecules placed into a spatially appropriate position to mimic FVIIIa, and recently this mimetic activity and the pharmacokinetics of the original antibody were improved by engineering the charge properties of the variable region within the immunoglobulin. Using the new antibody, termed ACE910, a phase 1 study in 64 Japanese and Caucasian healthy adults was performed and data from this trial suggested that the product had medically acceptable safety and tolerability profiles. The other new bypassing agent is named MC710, and consists of a mixture of plasma\u2010derived FVIIa and FX. Preclinical studies using <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> haemophilia B inhibitor monkey models indicated that the haemostatic effects of FVIIa and FX were enhanced by simultaneous administration. Results from phase I and II clinical studies suggested that MC710 had equal or greater pharmacokinetic (PK), pharmacodynamic (PD), efficacy and safety profiles than conventional bypassing agents in the treatment of joint bleeding in haemophilia patients with inhibitors. Another significant current issue in this context is the increased medical cost of conventional treatment due to the higher consumption of concentrates. Biosimilar products may offer advantages in these circumstances and may offer a less expensive alternative. Regulatory issues, however, together with acceptability of biosimilar materials and reimbursement policies as well as supply and demand incentives remain to be considered. Rare bleeding disorders (RBDs) have attracted less attention from the pharmaceutical industry than haemophilia or von Willebrand disease due to the limited number of patients involved. Many cases of this type have been treated, therefore, using fresh frozen plasma (FFP) or prothrombin complex concentrates (PCCs) which carry serious risks of infections, allergic reactions and fluid overload. Several specific plasma\u2010derived or recombinant products including fibrinogen, FVIIa, FXI and FXIII have now become available, however, and a phase III clinical study of recombinant FXIIIa has recently been completed demonstrating safety and efficacy of substances of this nature.<\/jats:p>","DOI":"10.1111\/hae.12413","type":"journal-article","created":{"date-parts":[[2014,4,25]],"date-time":"2014-04-25T09:03:49Z","timestamp":1398416629000},"page":"29-35","source":"Crossref","is-referenced-by-count":9,"title":["Novel products for haemostasis"],"prefix":"10.1111","volume":"20","author":[{"given":"M.","family":"Shima","sequence":"first","affiliation":[{"name":"Department of Pediatrics Nara Medical University Kashihara Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Hermans","sequence":"additional","affiliation":[{"name":"Division of Hematology Cliniques Universitaires Saint\u2010Luc Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"de Moerloose","sequence":"additional","affiliation":[{"name":"Division of Angiology and Haemostasis University Hospital of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,25]]},"reference":[{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2942"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057479"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12474"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0042-9007.2003.00365.x"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2009.12.010"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02548.x"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12024"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12205"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61139-2"},{"key":"e_1_2_3_11_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.32607\/20758251-2013-5-2-19-39","article-title":"Blood clotting factor VIII: from evolution to therapy","volume":"5","author":"Orlova NA","year":"2013","journal-title":"Acta Naturae"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-394411"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10198-013-0538-4"},{"key":"e_1_2_3_14_1","unstructured":"Directive 2001\/83\/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. Off J Eur Union 28 November 2001 L 311.2013."},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2013.09.014"},{"key":"e_1_2_3_16_1","doi-asserted-by":"publisher","DOI":"10.2165\/11593730-000000000-00000"},{"key":"e_1_2_3_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdm345"},{"key":"e_1_2_3_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-498261"},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12169"},{"key":"e_1_2_3_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02511.x"},{"key":"e_1_2_3_21_1","unstructured":"BrookerM.Registry of clotting factor concentrates. World Federation of HaemophiliaFacts and FiguresNo. 6 May. Ninth Edition 2012. 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