GAITHERSBURG, MD. — A Food and Drug Administration advisory panel on voted 6–1 that a novel device that uses thermal energy to ablate smooth muscle in the airway during bronchoscopy could be approved under certain conditions, as a treatment for severe, persistent asthma in people aged 18 years and older.
At the meeting, members of the FDA's Anesthesiology and Respiratory Therapy Devices Panel agreed that there was reasonable evidence that the device was safe and effective for this indication, but stipulated several conditions for approval, reflecting concerns about the need for longer-term safety and efficacy data.
The conditions included requiring the manufacturer to enroll all patients treated with the device after approval in a registry, which would follow the durability of the therapeutic effects and safety; and not using the device in patients with impaired coagulation or in those who are on anticoagulant medication, because hemoptysis was reported in six treated patients in the pivotal study.
Other conditions for approval were that physicians who use the device be adequately trained, and that patients not be retreated with the device until clinical trial data on the effects of retreatment are available. The panel also unanimously recommended postmarketing studies to further evaluate the safety and effectiveness of the device, with end points that include emergency department visits for respiratory symptoms, corticosteroid requirements, asthma exacerbations, and hospitalizations.
Components of the Alair Bronchial Thermoplasty system include a radiofrequency (RF) generator and a single-use catheter with an electrode basket at the tip that delivers RF energy to surrounding tissue. Treatment results in clinical improvements in people with severe asthma by using thermal energy “to reduce the airway smooth muscle responsible for airway constriction in asthma patients,” according to the device's manufacturer, Asthmatx.
The pivotal study conducted in six countries compared treatment with the device in 190 patients to sham bronchoscopy in 98 patients (where the catheter was deployed, without RF). Patients, whose median age was 41 years, had severe persistent asthma that was “not well controlled” (30%) or “very poorly controlled” (70%), and required high doses of inhaled corticosteroids and long-acting beta agonist therapy. Treatment was administered during three separate outpatient bronchoscopies 3 weeks apart. Each procedure took about 30 minutes, according to Asthmatx.
The primary end point was the average of the changes in 6-, 9-, and 12-month Asthma Quality of Life Questionnaire (AQLQ) scores, a patient self-administered validated questionnaire, from baseline. Scores increased among patients in both groups, but the average of the three scores was 0.21 points greater among those in the active treatment group, compared with those in the sham group, which just missed statistical significance, according to the FDA's analysis. The largest effects of treatment were seen at U.S. study sites, but in Brazil, improvements in the scores were somewhat higher among those in the sham group, which panelists agreed was a concern. Some panelists thought this may have been due to the free maintenance medications received by all the patients enrolled at the Brazil sites, possibly reflecting greater compliance with medication therapy.
Some of the study's secondary end points, including rates of severe exacerbations after treatment; days lost from work, school, or other daily activities due to asthma symptoms; and emergency department visits for respiratory symptoms, were lower among those treated with the device. Nearly 79% of those on Alair had a change in the AQLQ score of at least 0.5 (which the company said is the threshold for a clinically meaningful change), compared with 64.3% of those on sham treatment, the company reported.
Respiratory-related events, including asthma symptoms, were higher among those in the device-treated patients during the treatment phase (from the time of the first bronchoscopy through 6 weeks after the third bronchoscopy) but lower than among those in the sham group after that time. A total of six patients (3%) treated with the device had hemoptysis, which typically occurred soon after the procedure and was self-limited; one patient developed severe hemoptysis 31 days after treatment. But there were no cases in sham-treated patients. There were no treatment-related deaths or withdrawals for worsening asthma in the study.
Although the primary effectiveness end point in the pivotal study was not met, panelists supporting approval said they considered some of the secondary end points to be clinically relevant.
The panel generally agreed that the device appeared to be safe, but that long-term safety should be monitored, including the potential for dysplastic changes and malignancy in the treated areas. (There has been no evidence of structural abnormalities or neoplasia during up to 5 years of follow-up, according to Asthmatx.)