A device designed to help adults with the most severe cases of asthma – without the use of drugs – is getting closer to becoming available in the U.S. Results of the Asthma Intervention Research 2 (AIR2) trial of the Alair Bronchial Thermoplasty system, developed by Asthmatx (Sunnyvale, California), were reported today at ATS 2009, the international conference of the American Thoracic Society (New York), in San Diego. The Alair system is on track to becoming the first device therapy available for asthma patients in the U.S.

According to Asthmatx, the AIR2 results demonstrated statistically significant improvements in quality of life measurements and reductions in asthma attacks (severe exacerbations) and emergency room visits for respiratory symptoms in adults with severe asthma who underwent bronchial thermoplasty delivered by the Alair system.

"The reduction in asthma attacks and improvements in quality of life are consistent with the outcomes from previous trials," said Mario Castro, MD, a professor of medicine and pediatrics at the Washington University School of Medicine (St. Louis), and a principal investigator in the AIR2 trial. "These outcomes provide further clinical evidence needed to demonstrate the safety, effectiveness and long term benefits of bronchial thermoplasty."

The AIR2 trial was designed to evaluate the safety and effectiveness of bronchial thermoplasty in adult patients with severe asthma who were symptomatic, despite being treated with high doses of standard of care medications (high dose inhaled corticosteroids and long-acting bronchodilators). The study was a randomized, double-blind, sham-controlled trial and enrolled 297 patients at 30 sites in six countries. The primary effectiveness endpoint was the change from baseline in Asthma Quality of Life Questionnaire (AQLQ) score. Comparing the short and long-term safety profiles for both the treatment and sham control groups assessed safety, Asthmatx noted.

According to the company, the key statistically significant clinical findings of the trial were: improvement in the average AQLQ score at six-, nine-, and 12 months over sham control; four out of five Alair-treated patients responded with a clinically significant improvement in AQLQ compared to 64% of sham controls; 32% reduction in asthma attacks; 84% reduction in emergency room visits for respiratory symptoms; 36% reduction in patients reporting episodes of asthma (multiple symptoms) adverse events; and 66% reduction in days lost from work/school or other activities due to respiratory symptoms.

While investigators were expecting to reach the primary endpoints of the AIR2 trial, Castro told Medical Device Daily that he was somewhat surprised at the "pretty marked reduction in severe exacerbations of asthma and emergency room visits," because "typically studies have to be quite large with asthma to meet an endpoint like that."

In fact, those were the results that had the most impact with doctors and patients because they can relate to a number of ER visits more so than some of the other findings, Asthmatx CEO Glen French told MDD.

Bronchial thermoplasty is a non-drug procedure for asthma. The treatment is performed through the working channel of a standard flexible bronchoscope that is introduced through a patient's nose or mouth, and into their lungs. The tip of the small diameter Alair catheter is expanded to contact the walls of targeted airways. Controlled thermal energy is then delivered to the airway walls to reduce the presence of airway smooth muscle that narrows the airways in patients with asthma. The minimally invasive procedure, like many other flexible endoscopy procedures, is done under light anesthesia, and the patient returns home the same day, according to Asthmatx.

Castro told MDD that the treatment is actually delivered in three sessions: first in the right lower lobe of the lung; next in the left lower lobe; and the third in the upper lobes. The patient has to wait about two weeks between sessions to ensure that they are stable enough to go through the procedure, he said.

Asthmatx said that in the period immediately following bronchial thermoplasty, there is an expected increase and worsening of respiratory-related symptoms, which are of the type expected following bronchoscopy in patients with asthma. The company said these events typically occur within a day of the procedure and resolve on average within a week with standard care. In the long term, fewer bronchial thermoplasty treated patients reported respiratory adverse events and there was a significant decrease in patients reporting asthma (multiple symptoms) adverse events in the Alair-treated group compared to the sham control group.

"The results from AIR2, similar to the results from two prior randomized clinical trials evaluating the Alair system, demonstrate that patients with severe asthma can experience clinically significant improvements in their asthma control and their quality of life," French said.

The results of this pivotal study have enabled Asthmatx to submit a premarket approval application (PMA) to the FDA for regulatory approval, the company said.

"Participation in the AIR2 trial required an extraordinary level of involvement from all patients, and we were encouraged by the very high level of interest from patients who wanted to participate," Castro said. "This high level of patient interest and involvement in this complex and time-consuming trial reflects the substantial clinical need that exists for new treatment options in this population of patients with severe asthma."

The company has already filed the final module of its PMA application for the system and the FDA has granted it expedited review status (Medical Device Daily, Jan. 22, 2009). French said that in early April the agency had some questions related to the submission and that the company is in the process of answering those questions. Assuming its responses satisfy the FDA's inquiries, he said the next step would be to schedule an advisory panel meeting. Assuming that meeting goes well, and if everything else goes according to plan, Asthmatx hopes to introduce the device to the U.S. market early next year, French said. He said the company believes it has a "tremendous amount of clinical research" backing it up and has been collaborating with FDA for nearly a decade, fine-tuning the studies along the way. "This study means everything to the company, in a sense," French said. "It will determine for us if [the device is] sufficient to meet FDA's standards, which we believe it is."

The Alair system has received a CE mark for use in Europe, the company noted. Also, in 2006, bronchial thermoplasty was ranked fifth on the Cleveland Clinic's "Top Ten" list of medical innovations for 2007 (I>MDD, Nov. 10, 2006). That list marked the first of what has become an annual list from the clinic.

"The treatment we have available for asthma currently is primarily based on education and pharmacotherapy ... pharmacotherapy in this group of patients has really reached its limits in that it is still not achieving control of asthma symptoms," Castro told MDD. He said pulmonologists are looking forward to this device because it is something new they will be able to offer these patients to try to improve the control of their asthma symptoms. He also said doctors are looking for a therapy that is not associated with long-term adverse side effects as the current asthma treatments are.

So far, Castro said, the reaction to the Alair system from his colleagues in the field has been "overwhelming." The last time the company presented data on the device the room was packed and actually spilling out into the hallways, he said.

Castro emphasized the importance of this potential new asthma therapy by noting the seriousness of the problem for these types of patients. These patients are really disabled by their asthma, he said, and their quality of life is quite impaired.