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AIRFLOW-3 Data for Targeted Lung Denervation in COPD, with Gerard Criner, MD
Criner reviews findings from AIRFLOW-3 and describes the subgroup of targeted lung denervation treatment responders being targeted in AIRFLOW-4.
New trial data are shedding light on the potential impact of targeted lung denervation on chronic obstructive pulmonary disease (COPD) exacerbations.
Findings from the AIRFLOW-3 clinical trial were presented at the American Thoracic Society (ATS) International Conference 2025 by Gerard Criner, MD, chair and professor of thoracic medicine and surgery at Lewis Katz School of Medicine at Temple University and director of the Temple Lung Center.
The randomized, double-blind, sham-controlled study enrolled patients with symptomatic COPD (CAT ≥10) with moderate to very severe airflow obstruction (GOLD stage II-IV: 25% ≤ FEV1 ≤ 80% predicted, FEV1/FVC<0.70) and GOLD E status (≥2 moderate or ≥1 severe exacerbation in the prior 12 months) despite optimal medical therapy. The primary endpoint was a time-to-first event comparison of the probability of subjects having a moderate or severe exacerbation, between the treatment arm who received targeted lung denervation and optimal medical therapy and the sham control arm who received optimal medical therapy.
“There's been some preliminary clinical trials done outside the US that show the target of lung denervation in patients with COPD could have a significant effect, about 20% reduction in exacerbation severe enough to cause hospitalization,” Criner explained to HCPLive. “That was the rationale for why AIRFLOW-3 was designed with exacerbations as an end point in a patient group that had exacerbations in the past, either frequent, moderate or severe and were highly symptomatic with COPD assessment test scores that are greater than 10.”
A total of 388 patients at 32 clinical sites across the US, EU, and UK were randomized in a 1:1 ratio to the treatment and sham control arms of the trial. Patients were 67.8 (standard deviation [SD], 7.1) years of age, ex-smokers with a 46.7 (SD, 22.0) pack-year smoking history, and 41.0 (SD, 11.8) post bronchodilator FEV1% pred. Their SGRQ-C and CAT scores were 62.5 (SD, 17.0) and 23.6 (SD, 6.3), respectively. More than 90% of patients were on triple therapy at baseline and through 1 year of follow up, and 42% of patients had prior-year COPD hospitalization(s).
Findings presented at ATS showed AIRFLOW-3 did not meet its primary endpoint for moderate or severe exacerbations, with no significant difference observed between the treatment and sham control groups. Despite this, Criner highlights key physiologic findings demonstrating positive impacts of targeted lung denervation.
At 1 year, the sham arm exhibited a statistical decline in lung function, including a decrease in FEV1 and FVC, and worsening of gas trapping, as indicated by an increase in RV, whereas both were stable in the treatment arm. Additionally, results showed the treatment arm exhibited a statistically significant improvement in dyspnea at 1 year compared to sham, leading to the identification of a subgroup of targeted lung denervation treatment responders corresponding to an airway predominant phenotype that demonstrated clinically and statistically significant improvements in lung function and exacerbation frequency and severity.
“That's the subgroup that we're going to examine in an additional AIRFLOW-4 randomized control trial,” Criner said.
Editors’ note: Criner has relevant disclosures with APREO, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Pfizer, Pulmonx, Sanofi, and others.
