Exciting news for inhaled lung fibrosis therapies

Last year we made a series of posts highlighting the opportunities and challenges of developing inhaled therapies for idiopathic pulmonary fibrosis (IPF). In this blog, we provide an update on the most recent developments in inhaled IPF therapies.

To recap the opportunities and challenges, the inhaled route offers the advantage of delivering a medicine directly to where it is needed – the lung – to bring benefit in IPF, while avoiding the limitations of systemic side effects associated with oral administration.

With this background in mind, it is encouraging to see the progress being made in clinical evaluation of both inhaled pirfenidone (AP01) and inhaled nintedanib (AP02). As “normal” formulations administered orally as a tablet, these two agents are now established as the only standard of care (SoC) options in the treatment of IPF. However, side effects associated with this route of administration, due to high drug exposure in the GI tract and systemically, have proved to be significant limitations, with the result that the full potential of these treatments has not yet been realised. The hypothesis that this limitation can be addressed by inhaled delivery is being borne out by the exciting results reported recently for AP01 and AP02.

AP01 clinical trial results

Based on pooled trial data, the two most frequent side effects associated with oral pirfenidone are nausea (38%) and rash (25%). In the ATLAS trial, initially exploring 2 inhaled (nebulised) dose levels of AP01 in 91 IPF patients, the frequency of nausea and rash at the higher dose (100 mg twice daily) was 11.1% and 17.8%. With regard to efficacy, at the 24 week primary endpoint, mean Forced Vital Capacity (FVC) % predicted continued to decline at the lower dose, but remained stable in the 100 mg two times per day group. This led the Data Safety Monitoring Board to recommend transitioning all patients to the higher dose for the remainder of the trial.

AP02 clinical trial results

Top-line results from a Phase I clinical trial with AP02, involving 32 healthy volunteers and 6 IPF patients, have also been released. Inhaled delivery of nintedanib (0.5, 1, or 2 mg) was generally well tolerated, with no serious adverse events reported.

Challenges – local tolerability

However, among the challenges with inhaled delivery is the potential for airway irritancy. In the ATLAS trial with AP01 there was evidence in some patients of cough associated with nebulisation. These episodes were reported to be self-resolving or controllable through the use of salbutamol. In contrast to this acute effect, both doses of AP01 decreased the frequency of cough in IPF patients with high baseline cough frequency.

We continue to be enthused by the prospect of inhaled therapies in IPF, and are working with a number of clients in this field. If you feel that your project can benefit from our enthusiasm and experience please get in touch for an initial chat.

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