To date, about 165 biopharmaceuticals have gained marketing approval in the United States or Europe; approximately one in every four drugs introduced on the market is a biopharmaceutical.1 The term "biopharmaceutical," as used here, refers to recombinant therapeutic proteins, monoclonal antibodies used for therapeutic or in vivo diagnostic purposes, or nucleic acid-based products.
The global annual sales value of these products is about $33 billion, with recombinant erythropoietin (EPO) sales alone reaching $10.7 billion last year. Sales values of nonantibody-based therapeutic proteins are forecast to reach $52 billion by 2010,2 while sales values of therapeutic monoclonals will likely reach $16.7 billion by 2008.3 The biopharmaceutical market should approach or surpass $70 billion by the end of this decade.
In 2005, 10 biopharmaceuticals won approval in the United States or Europe. These were six hormones and growth factors, two antibody-based products, and two therapeutic enzymes (Table 1). Compared with previous approvals, this profile was somewhat out of the ordinary; there were no additional blood factors, anticoagulants, thrombolytics, interferons, interleukins, or recombinant vaccines. The profile of associated target indications also was atypical; for example, only one product (Avastin) was indicated for the treatment of cancer.
Only five of the 10 approvals are genuinely new molecular entities. Levemir and Kepivance, and Xolair and Avastin, although approved in Europe last year, gained approval before 2005 in some other world regions. The active biotech ingredient of GEM 21S, on the other hand, is identical to the active ingredient in Regranex, a product approved in 1997. In terms of expression systems used, four of the approved biopharmaceuticals are produced in mammalian cell lines and in Escherichia coli (E. coli). Two are produced in engineered Saccharomyces cerevisiae (S. cerevisiae), again confirming that these three expression systems are the workhorses of the biopharmaceutical industry.
Table 1. Biopharmaceuticals (defined as recombinant proteins, monoclonal antibody and nucleic acid-based products) approved in the United States or European Union in 2005.
In 2005, there were notable approvals of nonparenteral delivery systems and biosimiliars. Until last year, all approved biopharmaceuticals required to enter the bloodstream were administered parenterally. Parenteral drug administration, however, often results in reduced patient compliance and potential complications when in nonclinical settings. Fortical (Table 1) is the first biologic product delivered systemically by an alternative (intranasal) means. Nasal delivery is attractive because it is convenient. Also, the presence of high-density blood vessels, along with nasal microvilli, generates a large potential absorption surface area. Peptides and smaller proteins are often absorbed intranasally with acceptable bioavailabilities. Larger molecules—with a molecular mass greater than 10 kDa—are poorly absorbed through nasal membranes, so this approach is less attractive for many biopharmaceuticals.
In 2005, Omnitrope (a recombinant hGH produced by Sandoz (Princeton, NJ) became the first biosimiliar product to be approved in Australia, and this year won approval in both Europe and the US.
Last year had its downside, to be sure. Tysabri was abruptly withdrawn in February after only four months on the market for patent safety issues. In June 2006 it was reintroduced under altered, more limited indications.