Development and Licensing of Bio-Pharmaceuticals

Abstract

Biopharmaceutical products now represent a very important fraction of the total pharmaceutical market. The aim of this thesis is to provide an overview of biopharmaceuticals approved by the FDA and EMEA between 1995 and 2004, and to highlight trends in the development of the biopharmaceutical industry. Interferon beta is used as a case example to illustrate problems and opportunities in the licensing process, evaluation and marketing of a biopharmaceutical drug. Interferon also demonstrates the impact of the United States (US) government's orphan drug incentive scheme on pharmaceutical drug development. Biopharmaceuticals approved in the US and the EU over the last 10 years were searched within publicly accessible sources. These searches identified 147 biopharmaceuticals that were approved including 30 monoclonal antibodies, 32 vaccines and one antisense oligonucleotide. No gene therapy product was approved by either the Food and Drug Administration (FDA) or the European Medicines Agency (EMEA) during this period. Biopharmaceuticals account for 28% of all medicines approved in the US between 1998 and 2004 and 36% in the EU between 1995 and 2004. The biopharmaceutical industry is still small or medium sized. Biopharmaceuticals approved thus far are mainly protein-based agents for the treatment of life-threatening, chronic or rare diseases, e.g. cancer, severe infection, diabetes, autoimmune diseases and blood-related diseases. Several biopharmaceuticals have been advantaged by being licensed under the Orphan Drug Act; the Orphan Drug Act states that a rare disease needs to be either affects less than 200,000 persons or the cost of develop such a drug cannot be recovered from the sales. The evaluation of interferon beta products in this thesis shows that the market for an orphan product can be large and an orphan drug is not equal to non-profitable drug. Interferon beta was introduced in 1993 under the US Orphan Drugs Act. By 2003, worldwide sales of three branded formulations exceeded $2.87 billions. However, no direct comparison of efficacy is available between all currently marketed interferon beta products. Pre-marketing clinical trials submitted to the FDA for interferon beta products were searched. Odds ratios and 95% Cls were chosen as evaluation tools for comparison of efficacy between orphan products. The result shows that whilst demonstration of only one aspect of clinical superiority (that is, either safety or efficacy) is enough for the licensing of another orphan product, such a newly licensed drug may not offer superiority using different clinical endpoints. The financial risks linked with biopharmaceutical drug development are significant although the reward is huge. Biopharmaceutical companies should address how to assure the quality, safety and efficacy of new products in order to deal with new challenges in the near future, such as biogenerics.