Abstract

Affiliation: Laboratory for Biological Characterisation of Advanced Materials (LBCAM), Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland

Respiratory diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis or lung cancer constitute a huge burden in our society, and the global respiratory drug market currently grows at an annual rate between 4% and 6%. Oral inhalation is the preferred administration method for treating respiratory diseases, as it: (i) delivers the drug directly at the site of action, resulting in a rapid onset; (ii) is painless, thus improving patients’ compliance; and (iii) avoids first-pass metabolism reducing systemic side effects. In the most recent years, orally inhaled drug products (OIDPs) have found application also in the treatment of systemic diseases. OID Ps development, however, currently suffers of an overall attrition rate of around 70%, meaning that seven out of 10 new drug candidates fail to reach the clinic. During my presentation I will discuss some of the reasons behind the poor OID Ps translation into clinical products for the treatment of respiratory diseases, with particular emphasis on the parameters affecting the predictive value of animal preclinical tests. The key question that I will try to address in this presentation is whether there is value in using and refining current animal models for OIDP preclinical testing, or whether these should be relinquished in favour of new, more human-relevant non-animal methods. The preclinical methods currently available to test the efficacy [1] and safety [2] of new OID Ps for the treatment of uncurable respiratory diseases will be discussed, together with their limitations. The current advances in overcoming such limitations will be also reviewed, focusing on the adoption of in vitro, cell-based new approach methodologies (NAMs), such as the multilayered culture model of non-small-cell lung cancer we developed in our group [3,4].

References: 1. Movia D. et al., Animals, 2020, 10, 1259; doi:10.3390/ani10081259 2. Movia D. et al., Frontiers in Bioengineering and Biotechnology, 2020, 8, 549; doi.org/10.3389/fbioe.2020.00549 3. Movia D. et al., BMC Cancer 19 (1), 1-21; doi.org/10.1186/s12885-019-6038-x 4. Movia D. et al., Nature Scientific Reports 8 (1), 1-19; doi.org/10.1038/s41598-018-31332-6