Inhaled Pirfenidone Prevented Lung Function Decline in IPF

High-dose AP01 (inhaled pirfenidone) largely prevented lung function decline and was safe and well-tolerated during the first 24 weeks of a Phase 1/2 clinical study testing its use in patients with idiopathic pulmonary fibrosis (IPF).

Avalyn Pharma, the therapy’s developer, presented the results at the 2021 International Society for Aerosols in Medicine (ISAM) Conference, held May 22–26, in Boise, Idaho.

“We are pleased by the efficacy and safety profile we have seen to date with aerosolized pirfenidone in 91 patients over 24 weeks,” Bruce Montgomery, MD, CEO of Avalyn Pharma, said in a press release.

In the trial (ACTRN12618001838202) taking place in Australia, 91 participants were assigned randomly to receive either 50 mg once daily (46 patients) or 100 mg twice daily (45 patients) of AP01, via an investigational eFlow nebulizer system developed by Pari Pharma.

On average, individuals on the high-dose regimen saw no loss in lung function, as measured by changes in forced vital capacity (FVC), a lung function parameter that measures the total amount of air one is able to exhale after a deep breath. Meanwhile, those on the lower-dose regimen experienced a progressive drop in FVC.

The difference between FVC in each group was deemed statistically significant. It led the study’s data safety monitoring board to recommend a few months earlier that all participants be placed on the higher-dose regimen for the 12-month extension study that is to follow the initial 24-week (almost six months) treatment period of the main trial.

“The six month FVC data is very promising as well as the overall safety profile to date,” Montgomery added.

Both doses were safe and well-tolerated. Adverse side effects occurring in more than 10% of patients were rash (18%), upper respiratory tract infections (18%), and cough (24%). Fewer than 10% of participants experienced flu-like symptoms and gastrointestinal issues most commonly seen with Esbriet, an oral pirfenidone formulation marketed by Genentech that is currently approved for the treatment of IPF.

Avalyn also stated that most participants have volunteered to enter the study’s 12-month extension study, adding that it plans to present longer-term efficacy and safety data at an upcoming scientific meeting.

The company believes that its inhaled formulation of pirfenidone will prove more efficient than oral alternatives. Although oral anti-fibrotic medications like Esbriet and Ofev (nintedanib) are able to slow IPF progression, they must be administered in large doses — from which relatively little reaches the lungs — and resulting in substantial adverse side effects.

By delivering pirfenidone directly to the lungs, Avalyn expects to maximize the therapy’s medicinal potential, since lower doses, in theory, will be required to achieve a therapeutic effect.

“Despite the 2014 approval of two oral antifibrotic therapies, IPF and other fibrotic lung diseases remain fatal disorders with substantial unmet need,” Montgomery said. “We hope to confirm improved tolerability and long term efficacy with aerosolized pirfenidone in future Phase 3 trials.”