Table 1. Biopharmaceuticals (recombinant proteins and monoclonal antibody-based products) approved in the US or EU in 2006
The year 2006 witnessed the approval of 13 biopharmaceuticals in the United States or European Union (Table 1) including
four hormones, three antibody-based products, three therapeutic enzymes, one recombinant vaccine, an anticlotting agent, and
a nucleic acid–based product. Major target indications included hereditary genetic conditions (four products, three of which—Elaprase,
Naglazyme, and Myozyme—have orphan status), growth deficiency (two products), and neovascular macular degeneration (two products).
Only 10 of the 13 products were genuinely new to the market. Naglazyme, Tysabri, and Macugen, although approved in one region
last year, had gained approval before 2006 in some other world region.
Gary Walsh, PhD
In terms of expression systems used, five of the approved biopharmaceuticals are produced in mammalian cell lines, four in
Escherichia coli, and two in Saccharomyces cerevisiae, again confirming the prominence of these three expression systems in the biopharmaceutical sector. One product (Macugen)
is produced by solid-phase organic synthesis. Another (Atryn) is particularly noteworthy because it is the first biopharmaceutical
produced in a transgenic animal to gain regulatory approval.
Like 2005, last year also witnessed notable approvals in the context of nonparenteral delivery systems and biosimiliars. The
approval of Exubera (a recombinant insulin) marks a watershed for pulmonary-based biopharmaceutical delivery. The biosimiliar
product Omnitrope (recombinant human growth hormone), approved in 2005 by the Australian authorities, gained approval in both
Europe and the US in 2006. And the EU further underlined its acceptance of the principle of biosimilarity by approving a second
product (Valtropin, also a recombinant human growth hormone) last year.
The remainder of this article focuses on individual products approved in 2006, with product information detailed in a monograph
format. Information was drawn from regulatory sources1–3 and the Internet homepages of sponsoring companies. Because monographs detailing Naglazyme and Macugen were included in
previous articles4,5 they are not considered below. Although Tysabri also has been covered before4 , a revised monograph is included here because of the altered indications and restrictions linked to its resumed approval
last year.
PRODUCTS APPROVED
Quick Recap
Atryn (antithrombin alfa) is a recombinant form of human antithrombin (AT) produced by transgenic goats in their milk. The 432
amino acid single-chain protein is, like the native human molecule, glycosylated. It harbors four N-linked glycosylation sites
(Asn 96, 135, 155, and 192) and three disulfide linkages. The recombinant molecule displays significant differences in its
glycosylation profile compared with native human AT, both in terms of monosaccharide composition (for example, it is fucosylated
and less sialylated) and overall side chain structure. This influences the pharmacokinetics and heparin binding affinity of
the product.
The European Commission approved Atryn under exceptional circumstances in July 2006 because the rarity of the condition prevented
generation of comprehensive clinical data. The product is an anticlotting agent and is indicated for the prophylaxis of venous
thromboembolism in surgery of patients with congenital antithrombin deficiency. The original marketing authorization holder
was Genzyme Europe, but this has since been transferred to Leo Pharma (Ballerup, Denmark).
Associate Professor in the Industrial Biochemistry Program at the University of Limerick. He is also a member of BioPharm International's
Editorial Advisory Board.
Articles by Gary Walsh, PhD
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