Trial to assess device in severe emphysema, hyperinflation

Key takeaways:

• A variety of options/tools are needed when treating patients with severe emphysema and breathlessness.
• A phase 3 trial is investigating the BREATHE Airway Scaffold device in this patient population.

The BREATHE-3 trial hopes to determine the safety and impact of a novel bronchoscopic device on lung function in adults with severe COPD-related emphysema and hyperinflation, according to a press release from Temple Health.

In this multicenter, randomized, interventional, controlled, phase 3 trial, which treated its first patient in August, the release said researchers will enroll up to 250 adults aged 40 to 84 years with severe emphysema and hyperinflation in the U.S. and Europe to uncover the safety and efficacy of the BREATHE Airway Scaffold (Apreo Health).

This implantable and tissue-sparing device opens the airways and releases trapped air, according to the release. Notably, the BREATHE Airway Scaffold has received FDA breakthrough device designation.

Healio spoke with Gerard J. Criner, MD, FACP, FACCP, global principal investigator for the BREATHE-3 trial, chair and professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University and director of the Temple Lung Center, to learn more about current treatment options, how the BREATHE Airway Scaffold is different from other treatments and the hopes for the trial.

Healio: What are the current treatment options for patients with severe COPD-related emphysema?

Criner: For people with advanced lung disease, optimized medical treatments include the use of bronchodilators/bronchodilators with inhaled steroids if they have exacerbation risk factors; supplemental oxygen if there are criteria for oxygen use with severe resting or exercise-induced desaturation; physical therapy; rehabilitation and getting vaccines.

For people that have emphysema that remain symptomatic despite those measurements because they’re breathless and suffer from severe hyperinflation — lungs are too big for their chest wall, respiratory musculatures and heart function to be effective — they may be considered for lung reduction.

In the U.S., lung reduction takes two forms. One is lung volume reduction surgery, which is a therapy that’s been available to patients that meet certain criteria for lung function, CAT scan and other medical treatment since 2004. This has had poor uptake over the last 2 decades since it’s been available, mainly because of morbidity and mortality related to surgery. It’s also a somewhat complicated procedure to do outside of a center that’s equipped to take care of patients with advanced lung disease. It’s not done nearly as much as what it should be, and there are only about 170 to 175 patients done per year in Medicare beneficiaries.

Since 2018, there’s been less invasive procedures with bronchoscopic techniques that have been approved with endobronchial one-way valves. That has been effective to treat selected patients with improvement in lung function and quality of life. The problem with that therapy is you must meet certain criteria where the lobe that you’re treating has no evidence of collateral ventilation in regard to the adjacent lobe, either defined by fissure integrity or use of the flow probe for physiologic assessment. That ends up being about 30% of patients that are eligible for that therapy, but most patients are not. For those patients, only surgical therapy is available. Lung transplantation is also an option for selected people, but this is a much rarer commodity for patients with COPD, especially regarding their age or if they have a comorbid condition.

We are trying to solve these problems with airway stabilizer therapy and treat patients whether or not there’s collateral ventilation present or whether or not the fissure is intact.

Healio: Why are more options needed in this population?

Criner: The major thing patients with COPD, and especially those with emphysema, suffer from is breathlessness. Most patients complain that they remain breathless despite optimal medical treatment. In those cases, the therapies outlined above address the unmet clinical need, but there are probably more therapies that we need. Not all patients are the same. It’s a very heterogeneous patient population and because of that, you’re going to need different tools.

Healio: How does the Apreo BREATHE Airway Scaffold work, and how is this different from other treatments?

Criner: The current treatments for lung reduction have tried to modify the emphysematous tissue by cutting it out or resecting it; trying to deform it by collapsing it (the endobronchial valve is a good example); trying to make it smaller by using coils that retract and compress the lung tissue and reduce it inside; and by using heat to heat up the lung, cause inflammation and then scarring, which retracts the tissue over time. The BREATHE Airway Scaffold is different.

When you have normal lung tissue, the integrity of the lung tissue tends to pull the airway open, so the airway doesn’t collapse. In contrast, when you have emphysematous tissue that is diseased and loose, there’s nothing to keep airways in that area open. There’s no outward recoil from normal lung tissue, so they tend to collapse. They collapse closer to the main airways, and that means the regions beyond that collapse are areas of trapped gas.

What these airway stabilizers try to do is stent or open up the airway and keep it open by stabilizing the airway so it doesn’t collapse with respiration. You’re improving ventilation to the slow spaces of the lung and helping to deflate the individual by allowing that to happen.

Airway stabilizer therapy also has the potential of less morbidity. In the series to date that has been done outside the U.S., it didn’t have a risk for pneumothorax like we see with endobronchial valves, which carries about a 30% pneumothorax rate. It also is less prone for movement because there are five different lengths of the airway stabilizers. They’re anywhere from 40 mm to 100 mm, whereas the length of an endobronchial valve is about 7 mm to 12 mm. They also aren’t a lobar treatment like an endobronchial valve. They can create the segmental or subsegmental regions of the lung and don’t collapse the tissue, so they may not affect gas exchange as much.

Healio: What endpoints will you be evaluating in the BREATHE-3 trial?

Criner: The major endpoint is FEV₁. Secondary endpoints are measures of quality of life including the St. George’s Respiratory Questionnaire and the COPD Assessment Test. Exploratory endpoints include the 6-minute walk test.

Healio: What do you hope to uncover/determine through the BREATHE-3 trial?

Criner: If we have another tool to be able to improve patient’s quality of life by improving their lung function and the negative consequences of hyperinflation, which affects the lung, the chest wall and the breathing muscles in the heart, that would be a really useful treatment option for patients that aren’t sick enough to be considered for transplant or not a candidate for lung volume reduction surgery. It could also mean patients can avoid the morbidity and mortality of some of these procedures. We hope it can be applied in patients who aren’t candidates for those surgical interventions because their current clinical state doesn’t allow them to be subjected to such aggressive interventions.

Healio: When can clinicians expect to see trial results? Will there be interim analyses?

Criner: There won’t be an efficacy interim analysis. These trials usually take about 3 to 4 years to be concluded and published because you recruit several hundred patients and follow them for at least a year.

In the meantime, there’s multiple medical and device-related interventions that have tried to address the needs of patients with COPD and emphysema or without emphysema that have come about in the last 3 to 10 years. If patients feel like they’re not getting the treatment that is improving their status, they should talk to their doctors about other available treatments.

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For more information:

Gerard J. Criner, MD, FACP, FACCP, can be reached at pulmonology@healio.com.