The concept of delivering biologics – whether they be proteins, peptides, antibodies (or fragments thereof) or DNA oligomers – by the inhaled route has great appeal due to the opportunity to deliver locally high concentrations into the lung with the possibility of avoiding systemic toxicity. However, this has met with limited success (so far) with few products reaching the market place. Notable exceptions include the inhaled insulins (Exubera & Afrezza) and inhaled DNAse (Pulmozyme) to treat diabetes and cystic fibrosis respectively.
The past few years however have witnessed renewed interest in this route of delivery with most of the major pharmaceutical companies currently developing inhaled biologics programmes. This has been reflected in several toxicology and pathology conferences in 2017 showcasing inhaled biologics as part of their core agenda. The discussion at these conferences was vigorous, collegial and well received as it became increasingly apparent to pathologists and toxicologists alike that the response of the lung to biologics was even more complex and poorly understood than for low molecular weight molecules. In addition, the relative novelty of inhaled biologics meant that understanding was limited around what could be classed as a “typical” response to a proteinaceous material in the lung, all of which might hamper the route to clinical trials.
It was with this background that the BSTP devoted its annual scientific meeting to the topic of ‘Inhaled Biologics’ in November 2017 and perhaps not unsurprisingly, delegate discussion led to the suggestion of a White Paper to help understand this complex area of biology. It was from these relatively humble beginnings that we began the task of building a group to deliver one or two white papers that would address both the pathology and toxicology challenges arising from this route of delivery.
During the first quarter of 2018 an industry wide survey was submitted to the BSTP, ESTP, STP, AIT (Association of Inhalation Toxicologists) and BioSafe Societies to gather volunteers and poll available experience. The results were very encouraging (probably reflecting the underlying need within the industry). All the major pharmaceutical companies responded positively, and despite not having all the results back yet, we have more than 40 volunteers gathered from all corners of the industry – pharma, CROs and consultants. No doubt this figure will increase over the coming weeks. We also can report from the initial analysis of the survey that we have representative examples of all the major modalities and all the common toxicology species (including a few exotics ones too!). Thank you to all who have responded, volunteering their time, experience and (hopefully) information on their case studies – this is very much appreciated!
The real work now of assembling the working groups and putting pen to paper starts! No doubt the discussion will be lively and informative. From a pathology perspective, we are hoping that we’ll unravel some of the layers of complexity surrounding the response of the lungs to inhaled biologics. If we achieve this then both sponsors and regulators will be in a better position than where we stand today, with the opportunity to make more informed judgements on findings that start from a common position of understanding. From a toxicology perspective, we are hoping to discuss and review the specific challenges that come with dosing biologics and the different approaches and limitations in resolving these, and thus facilitate the conduct of high quality inhalation toxicology studies.
Peter Hall, Frank Brennan, Annick Cauvin, Karyn Colman, Sherri Dudal, Renaud Fleurance, Jo Kilgour, Alison Wolfreys