Biopharmaceutical therapies

Indeed, larger-scale, double-blind, place-bo-controUed chnical trials with Ad5FGF-4 (AGENT 3 and AGENT 4) are currently under way at centers throughout the world. These trials will characterize further the risk-benefit profile of the product, the optimal dose that should be administered, and the patient population likely to derive greatest benefit from this promising new biopharmaceutical therapy. 

Gene therapy is not, and will not be, an inexpensive therapeutic tool. The cost of such treatments will likely be broadly similar to the cost of present-day biopharmaceuticals. However, if proven successful in treating many currently incurable conditions, the cost beneht ratio will almost certainly greatly favour its medical use. 

In contrast to the biopharmaceuticals discussed thus far (recombinant proteins and gene therapy products), antisense oligonucleotides are manufactured by direct chemical synthesis. Organic synthetic pathways have been developed, optimized and commercialized for some time, as oligonucleotides are widely used reagents in molecular biology. They are required as primers, probes and for the purposes of site-directed mutagenesis. 

Despite tremendous innovations in the field of drug delivery technology, oral intake remains the preferred route of drug administration, for reasons of patient convenience and therapy compliance. Compounds intended for oral administration must have adequate biopharmaceutical properties in order to achieve therapeutic concentrations at the targeted site of action. 

The discovery of pharmaceuticals commences with the scanning of hundreds of compounds, whether with actual materials (irrational approach) or virtual simulations (rational approach). To discover biopharmaceuticals, we have to examine the compounds within us, for example, hormones or other biological response modihers, and determine how they affect the biological processes. In some cases, we study pathogens such as the influenza virus or bacteria to derive the vaccines. In other cases, we copy these biological response modifiers and use them as replacement therapy. 

Biopharmaceuticals are becoming increasingly important. The reason is that they are more potent and specific, as they are similar to the proteins within the body and hence are more effective in treating our diseases. There are three major areas in which biopharmaceuticals are used as prophylactic (preventive, as in the case of vaccines), therapeutic (antibodies), and replacement (hormones, growth factors) therapy. Exhibit 4.1 presents selected statistics for biopharmaceuticals. 

To date, most approved protein-based drugs are for therapeutic or replacement therapies. They are recombinant versions of natural proteins such as insulin and erythropoietin. Their characteristics and functions are relatively well defined and known. The next phase of biopharmaceuticals, such as antibodies and vaccines, is more complex and requires more tests and characterizations. Controls for the reliability, contamination, and fidelity of expression systems will be high on the agenda in the coming decade. 

As gene therapy and stem cell research progress, we can expect more regulatory requirements to be developed to ensure proper safeguards are implemented. Similarly, xenotransplantation and control of biopharmaceutical products will experience specihe regulatory controls as new advances are made. Exhibit 11.13 presents the FDA s current oversight on gene therapy and its cautious approach to cancer vaccine. 

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