Drug Delivery
Discovery and development of inhaled biopharmaceuticals
With the rapid generation of biological screening data and the potential for innovative selection of compounds for screening, the importance of multi- vendor collaborations together with improvements in automation has never been greater in terms of helping the drug discovery community as a whole.
By Dr Simon Moore, Dr Kirsty Harper and Dr Sylwia Marshall
T
he creation and subsequent development of inhaled biologics has become highly signifi- cant as it is now the route of choice for the delivery of numerous drugs. This is especially the case with biopharmaceuticals developed for the treatment of respiratory diseases. Primary drivers for this include the strong advantages that inhaled biologics have over parenteral routes. These include faster onset of action due to the large surface area (80-120m2) and good vascularisation of the lung; avoidance of degradation in the gastrointestinal tract and first pass effect improved therapeutic index due to targeted delivery requiring lower doses (with potentially fewer side-effects); improved patient compliance as it is more convenient, less intrusive and relatively comfortable for the patient; and, in some cases, has improved stability. Historically, challenges such as high drug requirement, manufacturing costs and stability issues have hindered the development of inhaled biopharmaceuticals. However, technological advances addressing these concerns are now facili- tating the development of such modalities. Pulmozyme® was one of the initial marketed inhaled biopharmaceuticals to move successfully through discovery and development to obtain
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approval in 1993 for use in the treatment of cystic fibrosis. There have been notable developments since then, with the field continuing to grow signif- icantly. Currently, there are in excess of 40 inhaled biopharmaceuticals in the public domain that have passed through the discovery stage and which are now in the early phase of development. The result of these discovery and development successes over the course of the last decade is that the percentage of biopharmaceuticals in the global pipeline has grown from 30% in 2010 to as much as 42% in 2017. Moreover, total revenues from their sale increased from 17% of all prescription drugs in 2010 to 26% in 2017, with the figures expected to reach as high as 30% by 2022. There is also strong likelihood that inhaled biologics will also make a significant contribution to the level of growth that has been projected.
There are a significant number of differences between new chemical entities (NCEs) and biolog- ics (Figure 1) and these heavily influence the over- all discovery and development strategies that are established including early-stage non-clinical safety assessment. This article highlights some of the key considerations for the development of inhaled bio- pharmaceuticals.
Drug Discovery World Winter 2017/18
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