The approvals profile mirrors several trends noted within the sector over the past few years. Antibody-based products continue to represent the single largest category of biopharmaceutical, with a total of 31 now having gained marketing approval. The global market for therapeutic antibodies was estimated at $5.4 billion in 2002 and is projected to reach about $17 billion by the end of the decade.4 The trend towards approval of engineered products also continues. Four of the six approved antibodies were engineered (one chimeric and three humanized) as were both insulin-based approvals. The insulin analog Levemir is particularly noteworthy. Its major engineered feature is the attachment of a fatty acid moiety to its amino acid backbone. Several older products have undergone such posttranslational engineering (e.g. pegylated interferons and products such as Cerezyme, which display altered glycocomponents), but Levemir is the first biopharmaceutical engineered by the attachment of a lipid group.
In terms of expression systems used to produce the approved biopharmaceuticals, seven of the biologically produced products are expressed in Chinese hamster ovary (CHO) or other mammalian cell lines, again confirming the dominance of these cell types in biopharmaceutical production. Two others are produced using Escherichia coli. Tysabri has gained the most attention of all products approved in 2004, for all the wrong reasons. It was on the market for less than four months when sales (and use in ongoing clinical trials) were halted for safety reasons.
Macugen may start a new trend in that it is the first aptamer approved for therapeutic use. Aptamers (also termed decoys) are relatively short nucleic acid-based sequences that adopt a three-dimensional structure capable of binding to, and thereby inhibiting, a specific target molecule. Reference 5 is an excellent review of the topic.
Advate Advate (octocog alfa) is a recombinant form of human blood factor-VIII produced in an engineered CHO-cell line. Its amino acid sequence is identical to that of the native factor-VIII. The product is quite heavily glycosylated, with 25 potential N-linked glycosylation sites and 12 O-linked glycans.
The European Commission approved Advate in March 2004. Advate is indicated for the treatment and prophylaxis of bleeding in patients with hemophilia A. The marketing authorization holder is Baxter AG. It is not a new molecular entity but a modification of the licensed factor-VIII product Recombinate (available in the US since 1992).