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Biotechnology products and indications I. Proteins
Published in Ronald P. Evens, Biotechnology, 2020
The coagulation proteins number 30, as listed in Table 8.6. Six companies market most of the products worldwide, that is, Bayer, CSL Behring, Novo Nordisk, Octapharma, Pfizer, and Takeda. Blood factors are very large proteins (thousands of amino acids in two chains [- A & B ]) and are involved in normal blood coagulation as cofactors in the coagulation cascade [Factor 7, F.8, F.9, F.10, F.13, and thrombin, plus von Willebrand factor]. The deficiency of any one blood factor, often a genetic deficiency, leads to serious bleeding disorders (hemophilia), but it is fully correctable through replacement therapy with these rDNA proteins. The factors are recombinant DNA proteins employing two possible hamster host cells, baby kidney (BKH) or Chinese ovaries (CHO). Factor 8 is available in 18 products, all with the same indication and use, and Factor 9 in 6 products. The original blood factors were short acting, but the use of pegylation (Adynovate, Esperoct, Jivi, Rebinym) and fusion proteins (e.g., Afystyla, Alprolix) extends the products’ half-lives substantially. Also, further molecular engineering of the protein domains, mostly B-domain deletion or truncation, creates additional molecules and products; however, the indications are the same as for the originator product. Other coagulation proteins are marketed for Factor 7 and von Willebrand deficiencies. These recombinant protein blood factors replace natural blood derivative products and avoid the potential viral contamination and immune reactions that were previously observed in these patients receiving blood derived products. Additionally, both a thrombin and antithrombin protein are marketed. An antidote to blood thinners is available as well, Andexxa. One coagulation protein (Atryn) is an antithrombin that involves manufacture in transgenic goats to produce the protein in their milk. Thrombocytopenia purpura has a protein therapeutic available (Nplate).
Emerging drugs for hemophilia A: insights into phase II and III clinical trials
Published in Expert Opinion on Emerging Drugs, 2021
Rurioctocog alfa pegol (BAX 855, Adynovate®; Baxalta US Inc., a Takeda company, Lexington, MA, USA), the first pegylated EHL product obtained by randomly conjugating a branched 20 kDa PEG molecule with a SHL rFVIII, was licensed in 2017 and achieved a 1.4-fold longer plasma half-life when compared to a SHL rFVIII products [61,62]. The second pegylated product, damoctocog alfa pegol (BAY 94–9027; Jivi®, Bayer, Leverkusen, Germany), a BDD rFVIII conjugated with a 60-KDa PEG molecule, was licensed in 2018 and achieved a1.5-fold longer plasma half-life than an SHL rFVIII products [61,62]. The most recently licensed (2019) pegylated product, Turoctocog alfa pegol (N8‐GP, Esperoct®; Novo Nordisk A/S, Bagsvaerd, Denmark), is produced by means of a site-directed glycoconjugation with a 40 KDa PEG of a B-domain-truncated rFVIII and demonstrated a 1.6-fold longer half-life than the previously used SHL rFVIII products [63].
Budget impact analysis of Jivi (damoctocog alfa pegol, Bay 94-9027) in severe hemophilia A in Japan
Published in Journal of Medical Economics, 2021
Teruhisa Fujii, Yuko Kidoguchi, Noriko Takahashi, Eric Yu, Dilinuer Ainiwaer, Aidan Byrne
Total market size was calculated based on the forecasted sales data (2020–2024) shared by Bayer for Jivi (BAY 94-9027), Kovaltry and Hemlibra, and expected share of the market for Jivi (BAY 94-9027) as a percentage of total sales. Proportions of the rest of the market occupied by Advate and Adynovate (Takeda) were estimated for 2019 and assumed to remain constant through 2020-2024. The relative proportions for each individual product were calculated and projected forward using the trend observed (i.e. Adynovate’s share is growing at the expense of Advate). The proportion of the non-Bayer and Hemlibra market that is occupied by each of the other comparators (Eloctate, NovoEight, Afstyla) was estimated for 2019 and was assumed to remain constant for 2020-2024. The relative proportion for each individual product was calculated and projected forward using the trend observed. For the scenario analysis where BAY 94-9027 has a higher market share uptake, the additional market share was gained at the expense of Advate and Adynovate. The shares of the comparators were assumed to be the same in the on-demand and prophylaxis market.
Prophylaxis for hemophilia A without inhibitors: treatment options and considerations
Published in Expert Review of Hematology, 2020
Leonard A. Valentino, Kate Khair
Currently approved FVIII EHL products use 1 of 2 approaches to extending factor half-life: Fc fusion – a single molecule of BDD rFVIII (Eloctate®; Bioverativ) is covalently fused to the human immunoglobulin G1 (IgG1) Fc domain [50,54]. The Fc moiety binds to the neonatal FC receptor (FcRn) and is recycled back into the circulation rather than directed to lysosomal degradation.PEGylation – the covalent attachment of polyethylene glycol (PEG) to rFVIII (Adynovate®, Takeda; Espercot®, Novo Nordisk; Jivi®, Bayer) protects it against proteolytic degradation, thereby reducing clearance and increasing circulating half-life [55,56].