Abstract

TherapeutAix has supported 20 respiratory projects: 16 in IPF, 3 in COPD, and one other. Nine were pursuing inhaled delivery. Given the known benefits, it is puzzling that inhalation is not being pursued more often in new therapies for IPF and the prevention/treatment of COVID-19. This is despite the precedent of inhaled bronchodilators and steroids, used singly or in combination, being the mainstay of pharmacological management of asthma and COPD. 

We suspect the explanation is a mix of perceptions of difficulty, nervousness regarding doing something different, and a lack of awareness of the benefits.

In IPF, there is a perception that inhaled drug delivery could be compromised. However, lung distribution studies have shown good drug delivery to the peripheral airway in IPF patients can be achieved. There is also the reality that a new therapy, at least initially, would likely need to be an "add-on" to standard of care. Given the side effects (SEs) with both oral pirfenidone and nintedanib, adding new oral therapies will likely lead to additive SEs. Inhalation, with reduced GI and systemic exposure, provides a promising means to enable add-on therapies.

Treatment of SARS-CoV-2 infection would ideally target the respiratory tract and airway epithelium rapidly and aggressively, nullifying viral entry and replication before it becomes established. With oral delivery, airway exposure and effect depend on systemic PK; multiple doses may be required to achieve effective concentrations (EC_90/95). However, with inhaled delivery, airway exposure and efficacy are rapidly achieved with a lower total dose and systemic exposure and reduced systemic SEs. 

In conclusion, current (mis)perceptions and limited awareness of the benefits of inhaled delivery may hinder optimal treatment approaches in respiratory diseases. The potential for inhaled administration should be evaluated early in drug discovery projects.