Until recently, the primary options for patients diagnosed with advanced emphysema included lung volume reduction or a lung transplant. Such surgeries have limited eligibility because of their complexity and — in the case of lung transplants — because available organs are sometimes hard to come by.

But in the past six months new investigational procedures have emerged for patients with the most severe cases of emphysema, including one that involves poking small holes in a patient’s lungs and another that involves redirecting air flow from diseased portions of the lung to healthier areas.

Now another potential treatment — one that involves isolating the targeted diseased portion of the lung to allow healthier portions to function more normally — is under expedited FDA review.

Emphasys Medical (Redwood City, California) said its pre-market approval (PMA) application for its Zephyr Endobronchial Valve (EBV) has been accepted as “suitable for filing” by FDA and has been granted expedited review.

According to the company, FDA granted expedited review based on the potential of endobronchial valve treatment to offer a viable alternative to surgery in some emphysema patients, and the lack of a therapeutic device to address this potentially life-threatening or irreversibly debilitating disease.

The Zephyr EBV is a small one-way silicone valve inserted into airways to prevent air from entering the diseased portion of the lung during inhalation, while allowing air and fluids to escape during exhalation. The Zephyr EBV is intended to mitigate the effects of emphysema by isolating the targeted diseased portion of the lung, causing a reduction in volume of the diseased region and allowing the healthier portions of the lung to function more normally.

Mark Murray, CFO of Emphasys, told Medical Device Daily the company could not comment on the device or PMA application beyond what is in its news release because it is in a quiet period following its filing with the Securities and Exchange Commission for an initial public offering.

The company in September reported filing with the SEC to raise up to $86.3 million in its IPO (Medical Device Daily, Sept. 25, 2007).

Emphasys said in its SEC filing that it expects approval for its Zephyr EBV in late 2008. The company said the device has also been used for the treatment of lung air leaks in limited circumstances under a compassionate use protocol approved by the FDA on a case-by-case basis. Procedures using the Zephyr EBV are potentially reversible, if necessary, and the valves can be removed with standard bronchoscopic tools, the company noted.

Emphasys joins at least two other companies — Broncus Technologies (Mountain View, California) and Spiration (Redmond, Washington) — in developing new techniques to offer emphysema patients a shot at breathing easier.

In July, Broncus reported starting its Exhale Airway Stents for Emphysema (EASE) trial to explore an investigational procedure called airway bypass, which uses drug-eluting stents to keep the new pathways in the lung open for trapped air to escape — in other words, it involves poking needle-sized holes in the patient’s lungs. This in turn may relieve severe emphysema symptoms such as shortness of breath, the company said (MDD, July 5, 2007).

The results of Broncus’ open-label Exhale drug-eluting stent feasibility study were published in the October issue of the Journal of Thoracic and Cardiovascular Surgery. Positive results from that study include a statistically significant reduction in the amount of air trapped in the lungs and an improvement in breathing for patients at six months after the airway bypass procedure (MDD, Oct. 16, 2007).

Spiration began enrolling patients in its IBV Valve trial in the U.S. in September. The purpose of the trial is to generate safety/effectiveness data to seek FDA approval for the treatment of severe emphysema (MDD, Sept. 26, 2007).

The company’s IBV Valve System is designed to redirect airflow from diseased portions of the lung to healthier areas. During a minimally invasive procedure, a catheter is passed through a bronchoscope (a flexible tube passed into the bronchial tubes through the mouth or nose) to deploy the small umbrella-shaped valves into the airways of the upper lobes of the lungs.

The IBV Valve Trial is a prospective, randomized, blinded clinical trial that will enroll up to 500 patients at up to 40 sites in the U.S. The primary endpoints will be measured at six months.

Emphasys submitted its PMA application to FDA in mid-September, based on data from its pivotal trial, the endobronchial Valve for Emphysema palliatioN Trial (VENT).

VENT was a randomized, multi-center trial enrolling 321 patients with severe heterogeneous emphysema. The trial design was based on input from a panel of expert clinicians convened by the FDA in February 2003 to help establish the appropriate clinical endpoints for medical device treatments of emphysema. The VENT study’s primary efficacy endpoints were improvement in lung function as measured by forced expiratory volume in one second (change in FEV1) and exercise tolerance as measured by a six minute walk test (6MWT) both at six months. The primary safety endpoint was a composite of major complications at six months.

VENT met both its primary efficacy endpoints showing statistically significant improvements in lung function (p=0.0047) and exercise tolerance (p=0.0073), the company said. VENT also showed that the Zephyr EBV has a favorable safety profile in comparing major complications between the treatment and control groups.

At the six-month follow-up, protocol-defined major complications occurred in 5.9% of treated patients compared to 1% of control patients who received standard medical management. The difference did not reach statistical significance, the company noted. Investigators also reported on select patient subsets. In patients defined as having physiologically isolated target lung zones and correct Zephyr EBV placement, FEV1 was increased by 21% (p<0.0001).

Emphasys said the Zephyr EBV is CE marked and has been sold on a limited basis in Europe and in certain Asia-Pacific regions including Australia, Hong Kong and Singapore.