Medical Device Daily National Editor

Breathing room.

That's what a new device system from Asthmatx (Sunnyvale, California) is designed to provide, by preventing the airway blockages that create the gasping, wheezing and suffocation that characterize asthma.

And with $50 million and more of investment support, Asthmatx has considerable breathing room on the road to winning approval for its Alair Bronchial Thermoplasty system.

And because, according to the company, the Alair will offer the only device therapy for treatment of asthma, it can claim considerable competitive breathing room as well.

Asthmatx last week reported filing of the final module of its PMA application for the system for treating severe asthma. Importantly, the FDA has granted the system expedited review status.

The breathing difficulties of asthma are the result of blocked airflow to the lungs, the result of airways in the lungs squeezing shut. No cure, no method of preventing this, has been found. It can only be reversed for awhile with a combination of pharmaceuticals, including inhalers for long-term and short-term relief.

But these drugs frequently lose their effectiveness, with Asthmatx initially targeting those lacking control with the use of drugs.

An estimated 20 million in the U.S. have asthma, and the company is targeting the 15% of adult suffers whose asthma is poorly controlled by drugs, or about 2 million. Asthma kills an estimated 4,000 annually, with reports of people found dead, clutching their inhalers. At least one of the most popular inhaled drugs, Advair, has been associated with an increased risk of death.

As an alternative to drug therapy, the company's device strategy is built on the concept that if you reduce the ability of the airways to constrict, you maintain better air flow and increase the number of symptom-free days for the asthma patient.

And the apparent strength of Asthamtx's early research has resulted in a $50 million investment from Olympus (Tokyo), plus subsequent equity investments.

Gren France, CEO of Asthmatx, told Medical Device Daily that the company has been in a sort of semi-stealth mode, not withholding information about itself but also not pushing for publicity because investors are coming to it.

France declined to reveal the total cash raised by the company but said that its funding could be put "between $50 million and $100 million," likely to carry it through to product commercialization, assuming approval.

The Alair system works by delivering thermal energy to the smooth muscles of the airways and limiting their ability to constrict.

"Our concept was, if we would be able to reduce airways restriction in these ... high-flow, high-velocity airways [of the lungs] it would increase flow through the system."

In operation, a catheter probe is delivered down the mouth or nose to these airways in a standard endoscopy approach – the patient given light anesthesia – and a series of rib-like structures at the tip of the probe are expanded against the airway walls, with the thermal energy delivered against them.

Called bronchial thermoplasty, the procedure is delivered in three separate treatments – to the right lower lobe, then to the left and then to both upper lobes of the lung - and the patient able to leave the office and resume normal activities after each treatment.

The first module of company's PMA application was filed last July, and the third and final module was submitted on Dec. 30. The PMA submission is based on one-year data on 297 patients from the company's Asthma Intervention Research 2 (AIR2) pivotal trial.

France told MDD that Asthmatx will release data details from the AIR2 trial at the May annual meeting of the American Thoracic Society (New York) in San Diego and that it is preparing a manuscript for publication.

Characterizing the AIR2 results, he said that the device has demonstrated the ability to provide up to 90 days of asthma-free symptoms, beyond the patient's ordinary experience, to those with asthma that is poorly controlled by drugs.

In the trial, patients in the control group went through a sham treatment, with a team evaluating these patients in recovery unaware of which patients received the sham, which the actual, treatment.

The primary effectiveness endpoint was the change from baseline in Asthma Quality of Life Questionnaire score. Safety was assessed by comparing the short and long-term experience for both groups.

In earlier research concerning the Alair, reported in a July 2008 issue of the New England Journal of Medicine, 112 subjects were treated with either the Alair or sham. The treated group had a reduction in asthma symptoms, showed greater morning peak expiratory flow, had an increased number of symptom-free days and needed fewer puffs of their "rescue"-type inhalers.

The company says that following bronchial thermoplasty there is often an increase of respiratory-related symptoms but that these "resolve on average within seven days with standard care." And according to the data in the NEJM study, the after-procedure symptoms were no different between treated and control groups.

French said that the FDA's granting of expedited review might more quickly bring to patients what he called "a breakthrough technology" targeting a disease need that is "indisputable."

The total clinical experience with the Alair system includes, to date, more than 800 bronchial thermoplasty bronchoscopies with long-term follow up data available. "We have," French said, an extraordinary amount of clinical experience across disease severity and follow-up out to five years."

"We are encouraged by the consistency of the data that we have seen across four clinical studies in patients with asthma," said Gerard Cox, professor of medicine at McMaster University (Hamilton, Ontario), and an investigator in the company's four bronchial thermoplasty studies. "The results of the randomized trials show a significant and persistent improvement in asthma control and quality of life in patients with severe asthma."

The singular status of the company's technology perhaps works to some disadvantage by not having reimbursement codes in place, but France noted the large benefits of the device – reductions in doctors' visits, emergency room trips (estimated at 2 million yearly) and hospitalizations (an estimated 500,000 yearly) and the need for fewer drugs. And he noted that the device addresses one of those chronic components of illness that soaks up 80% of the healthcare dollar.

All of these advantages point to likely coverage by the Centers for Medicare & Medicaid Services.

He also suggested that while the company is initially focused on severe disease, this could be expanded to more moderate illness.

The question of to usefulness in children is more tenuous, France acknowledged. He called that population "a different animal" with a different anatomy, requiring considerably more modification and testing of the device.

France said that Asthmatx is hoping for FDA approval and then U.S. product roll-out early in 2010 and that this will drive ramp-up of infrastructure for sales in Europe, where the system already has the CE mark.