FDA Advisers Recommend Rejection of Airway Valve for Emphysema
By Emily P. Walker, Washington Correspondent, MedPage TodayPublished: December 05, 2008Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

GAITHERSBURG, Md., Dec. 5 -- An FDA advisory panel recommended today against agency approval of a first-of-its-kind one-way airway valve for emphysema patients, a device billed as a noninvasive substitute for lung volume-reduction surgery.
By an 11-2 vote, the Anesthesiology and Respiratory Therapy Device Panel found insufficient evidence of benefit to outweigh the risks of implanting the Zephyr Endobronchial Valve, manufactured by Emphasys Medical of Redwood City, Calif.
The panel was chaired by anesthesiologist David Birnbach, M.D., M.P.H., of the University of Miami. The affirmative votes were from two pulmonologists, Andrew Reis, M.D., of the University of California San Diego, and Philip Marcus, M.D., of the University of Arizona in Tuscan.
Drs. Marcus and Reis argued that the panel should recommend approving the device with some caveats, such as demanding an immediate post-market study, but the panel voted against approving the device with added conditions.
"Once you approve, the cat is out of the bag," said panel member Hugh Cassiere, M.D., director of the cardiothoracic unit at North Shore University Hospital in Manhasset, N.Y. "Approving a product just to continue research is not justified," he said.
But panel members seemed as upset as the company with the decision.
"It kind of breaks my heart to vote against this," said Stephen Li, Ph.D., of the Medical Device Testing and Innovations in Windsor, N.J. "The panel recognized how few options exist for emphysema patients."
"It's an interesting technology that is not ready for prime time," said panel member Thomas Vassiliades, M.D., of Emory in Atlanta, a cardiothoracic surgeon.
The FDA is not obliged to follow an advisory panel's recommendations but it usually does.
The Zephyr device is a removable one-way valve that is implanted by fiberoptic bronchoscopy into the diseased lobe in the lung. The purported mechanism of the valve is to reduce thoracic gas volume by preventing air from entering while still allowing trapped gas to escape.
The device limits the amount of air intake for an emphysema patient, and offers an alternative to the more risky lung volume reduction surgery for some patients, said pulmonologist Frank Sciurba, M.D., of the University of Pittsburgh, who was principal investigator for the key clinical trial, VENT.
For the Endobronchial Valve for Emphysema Treatment Trial (VENT), researchers randomized 221 patients to receive either the Zephyr endobronchial valve, or standard treatment. The tria l was multicenter, prospective, and unblinded.
The primary efficacy endpoint was at least a 15% change from baseline on two respiratory tests. The first test measured how much a patient could breathe out in one second while breathing as fast as possible, and the second tested how far a patient could walk in six minutes. Patients had these two tests at one, three, six and 12 months post-valve implantation.
The trial prespecified the six-month follow-up as the time to use to determine success of the treatment. At six months, the groups receiving the valve performed better on both tests than the control group (P=0.002 for breath test and P=0.019 for walk test), although the difference was much less than the prespecified 15% improvement.
At 12 months, the results of the 6-minute walking test dropped below statistical significance. Other secondary tests, including one to gauge quality of life, were also no different between the two arms at one year.
But perhaps the most striking result, according to pulmonologist Deborah Shure, M.D., Master FCCP, a consultant for the FDA, was the number of deaths in the valve group at six months. While no deaths were reported during that period in the control group, six patients died in the valve group before the half-year mark. All but one of those deaths was COPD-related. Dr. Shure gave a clinical review of the trial before the panel.
The mortality differences between the two groups are not so alarming considering that the valve group had twice the number of patients as the control group, said Armin Ernst, M.D., an interventional pulmonologist at Beth Israel Deaconess Medical Center in Boston, who spoke on behalf of Emphasys Medical. The company determined that there was not an increased mortality in the valve group.
But mortality rates aside (which were similar in the two arms at one year), other serious negative outcomes appeared to hit the valve group harder at the one-year mark.
The valve group had higher rates of serious adverse events related to COPD than the control group (23% versus 10%, P=0.01). They were also more likely to be hospitalized (39.7% versus 25.3%, P=0.024).
Ultimately, the panel agreed that the safety of the device was not the biggest issue.
"The risks are not huge," said Dr. Vassiliades, the panel member. "They are not insignificant either." But "the benefits are inadequate to overcome the risks."
"It's an irreversible disease," said Dr. Marcus. "What else can we really offer these people?"
The lead researcher of the trial said Emphasys likely will not continue on with its research.
"This was an $80 million study," said Dr. Sciurba. "There will be no resources for this company to complete it, and I fear this technology will die."
He said there are several other companies with similar technology, but this was, by far, the farthest along trial. (See: CHEST: Investigational Valve May Help In Emphysema)
"I feel it's a loss for choice in an otherwise bleak situation," Dr. Sciurba said after the vote.
Dr. Sciurba said he received no consultation fees from Emphasys. He is also an investigator on the NIH-sponsored National Emphysema Treatment Trial.