Therapeutics
New tools to enhance the antibody drug pipeline
Therapeutic antibodies are the fastest growing class of drugs, with continuous increases in the number of innovator and biosimilar drugs in development. Drug development and clinical trials necessitate the ability to specifically, sensitively and reproducibly measure the concentration and bioavailability of these drugs in pharmacokinetic assays. We discuss the rise of therapeutic antibodies in drug discovery in favour of traditional small molecules and issues around the development of these biologics, including their tracking with anti- idiotypic antibodies. We will examine new tools that are entering the market to offer solutions that can speed development timelines and address problems of reagent reproducibility.
By Dr Robert Ford and Dr Toni Hoffman
B
iological therapeutics continue to demon- strate viability and effectiveness, along with excellent safety profiles within the clinic. Combined with an increased financial return on investment, the incentives for the pharmaceutical industry to develop these technologies as new ther- apies are clear. As research yields an increased number of viable disease biomarkers, developing new drugs to these targets is the next step in bring- ing these discoveries to application. Additionally, patents on many successful biologics currently available in the clinic are beginning to expire, including trastuzumab for breast cancer treat- ment1, adalimumab for rheumatoid arthritis treat- ment2 and bevacizumab for the treatment of many cancers such as colon and lung cancer3, raising the prospect of a lucrative biosimilar market. The rise of biological therapeutics has created a concurrent increased need for tools for their specific analysis within patient samples. It is essential to be able to monitor the level and distribution of poten- tial therapeutics in animal models in pre-clinical studies, and in patients throughout clinical trials. However, high levels of endogenous antibodies are present within the serum, sometimes in up to a mil- lion-fold excess4, potentially masking the biothera-
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peutic molecule. Consequently, highly-specific and sensitive reagents are key for enabling the specific detection and accurate quantification of the thera- peutic antibody within patient serum samples.
Anti-idiotypic tools and essential characteristics
Anti-idiotypic reagents (anti-ID), including anti- gens, antibodies and anti-ID antibody mimetics, are the specific tools that enable monitoring of therapeutic antibody levels and their distribution within pharmacokinetic (PK) assays. An idiotope is a specific set of unique antigenic determinants, typ- ically found in the variable portion of an antibody, which defines that particular antibody in contrast to all other antibodies. An anti-ID antibody can specifically bind to the idiotope of the target anti- body, such as a therapeutic antibody, to act as a capture or detection reagent in PK assays. Bioanalytical scientists can generate a variety of data through use of anti-ID antibodies, such as quantification of bound drug, free antibody, or total drug levels. Developing such highly-specific anti-ID reagents can be challenging, and develop- ment of anti-ID antibodies is often time-consum- ing, with poor success rates5-8. Additionally, the
Drug Discovery World Winter 2017/18
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