In the first blog of this series1, we highlighted that, despite the potential advantages, there appear to be only a few opportunities pursuing the inhaled route of delivery in IPF. Our perception is that there is a “double whammy” here – a general nervousness in the Pharma and Investor community regarding inhalation per se and some specific concerns regarding inhaled delivery in IPF.
On the general point, there is no doubt that optimising molecules for inhaled delivery is not straightforward. It is better considered in an integrated manner early in a discovery project, rather than as an afterthought. Even though direct lung delivery may reduce systemic side effects, it is also the case that inhaled delivery can bring a new set of side effects that need to be factored-in to the overall efficacy/safety/adherence equation – for example, a 24% frequency of cough with the nebulised formulation of pirfenidone we mentioned last time2. While upper airway irritancy is a potential complication of inhaled delivery, not all device and formulation options are the same in this respect. So if there is a significant issue, there is a high likelihood of detecting, understanding, and de-risking this early in the clinical programme.
On the IPF-specific front, we have heard many times of a – maybe intuitive – perception that efficient inhaled drug delivery could be compromised in IPF patients. However, lung distribution studies with salbutamol (used as marker compound) showed that it is possible to achieve and optimise drug delivery to the peripheral airway in IPF patients3. There are also some elegant examples of translational pharmacology studies in this space, notably with the αvβ6 inhibitor, GSK30083484. It appears that this compound is no longer being progressed, but it provides a useful template for validation of target and delivery route.
A really important factor in future treatment of IPF, which we highlighted in our recent review5, is that, at least initially, new approaches will need to be compatible, as add-on therapy, with the current standard of care. Given the significant side effects already associated with both oral pirfenidone and nintedanib, add-on of new mechanisms via the oral route is highly likely to lead to additive side effects. Inhalation, by virtue of reduced GI and systemic exposure, may represent the only means to enable the add-on potential for a number of new approaches.
We know of a number of companies considering inhaled delivery in IPF. However, they are struggling to gain traction and attract investment due to some of the perceptions outlined above. If you are one of those companies, we are confident that we would be able to help you in your efforts. And to Investors, we would welcome the opportunity to discuss the benefit/risk equation for inhaled delivery in IPF. Do get in touch to start the discussion!
You can read our other blogs from the series here: