Avalyn Presents AP01 Pulmonary Fibrosis Data at ATS 2024

Avalyn Pharma Inc., a biopharmaceutical company at the clinical stage, has recently presented promising clinical data for AP01, an inhaled formulation of pirfenidone. This data supports the advancement of AP01 into a Phase 2b trial aimed at treating progressive pulmonary fibrosis (PPF). Avalyn’s ongoing ATLAS open-label extension study shows that AP01 treatment stabilizes forced vital capacity (FVC) in patients with both idiopathic pulmonary fibrosis (IPF) and PPF, while offering better safety and tolerability than the oral version of pirfenidone. Post-hoc analyses, looking at disease progression and Brainomix’s e-Lung biomarker scores, back the chosen dosages of 100 mg twice-daily and 50 mg twice-daily for the upcoming Phase 2b study.

The findings were shared through various poster presentations at the 2024 American Thoracic Society (ATS) International Conference, held from May 17-22 in San Diego, CA.

Dr. Howard M. Lazarus, Chief Medical Officer at Avalyn, expressed the critical need for new treatments that are both effective and tolerable for long-term use. He emphasized that pulmonary fibrosis is a debilitating and often lethal condition, even with current oral therapies. The long-term data for AP01 is encouraging as it suggests better efficacy and safety, potentially leading to improved patient outcomes.

Avalyn’s open-label extension study involved 100 patients divided into three cohorts. These included 41 patients with IPF who had previously been treated with AP01, 31 AP01-naïve IPF patients, and 28 AP01-naïve PPF patients. All participants were administered 100 mg of AP01 twice-daily. The study revealed that patients treated with AP01 exhibited a significantly lower annualized change in FVC compared to historical data with oral pirfenidone.

For those in the roll-over IPF cohort, the annualized change in FVC was -107 ml/year over 180 weeks. This is notably lower than the -235 ml/year observed with oral pirfenidone in prior trials. Similarly, AP01-naïve IPF and PPF patients showed annualized changes in FVC of -134 ml/year and -13 ml/year, respectively, over 84 weeks. As of now, 47 patients across all cohorts continue to receive AP01 treatment, with some having been on the therapy for up to 252 weeks.

AP01 has generally been well-tolerated, leading to lower reported rates of side effects such as nausea, rash, diarrhea, fatigue, dyspepsia, and vomiting, compared to oral pirfenidone.

In a post-hoc analysis of the ATLAS Phase 1b study, it was found that AP01 (100 mg twice-daily) reduced the risk of disease progression in IPF patients, defined as a decline of more than 10% in FVC. By 48 weeks, only 21% of patients in this dosage group experienced such a decline, compared to 35% in the 50 mg once-daily group. Favorable trends for the higher dosage group were also observed at 12 and 24 weeks. This supports Avalyn’s dosing strategy for the planned Phase 2b trial.

Avalyn and Brainomix presented data on e-Lung imaging biomarkers, using Brainomix’s AI-enabled computed tomography (CT) processing software. The analysis showed that the weighted reticulovascular score (WRVS) substantially correlated with future IPF progression risk. Patients receiving 100 mg of AP01 twice-daily showed stabilization trends in both WRVS and FVC, indicating that e-Lung WRVS might help identify disease progression risk and treatment effects.

Avalyn Pharma is dedicated to developing inhaled therapies for rare respiratory diseases like pulmonary fibrosis, which is marked by scarring, lung function decline, reduced exercise capacity, and increased mortality. Current therapies slow disease progression but come with significant side effects. Avalyn aims to reduce these toxicities by delivering medication directly to the disease site through inhaled formulations. AP01, their lead program, has shown improved efficacy and safety over existing treatments in clinical trials.