FDA Scores Big Piece of the Blame

Emphasys Medical Inc., developer of an endobronchial valve, put itself up for sale this week following a rough couple of months. (VentureWire Lifescience had the first report.) It’d be easy to hold the economy responsible for the company’s fate. But CEO John McCutcheon is serving the biggest piece of blame pie to the Food and Drug Administration.

Emphasys executives were shocked in December when the FDA's anesthesiology and respiratory therapy device panel voted 13-2 vote against recommending approval of the Zephyr Endobronchial Valve. In the panel's eyes, the device showed promise, but it didn't work well enough to warrant approval. (It's worth noting the two dissenting panel members--those that favored approval with conditions--also happened to be the board's only two pulmonologists.)

Prior to the meeting, Emphasys led the pack of device companies developing new methods of treating sufferers of late-stage emphysema. The valve is used to block airways leading to diseased lung tissue, effectively reducing the volume of the lung, allowing patients to breathe more easily.

Company executives walked into the hearing room carrying six months of data showing the device hit the endpoints laid out in the clinical trial design. Patients could breathe more effectively and showed greater endurance in six-minute walks. (We’ve got lots more on this in our December issue of IN VIVO.)

But the agency countered with data collected at 12 months after the implantation, where patients were breathing better but did poorly on their endurance tests. The panel also considered other measures of "clinical importance" into consideration. Overall, the agency's reviewers said the Zephyr fell short.

McCutcheon says the agency sought analysis of six months of data and received analysis of six months of data, saying the slipping endurance scores could be explained by the general poor health of the patient. He also noted that patients with late-stage emphysema really have no other options for treatment, so even a device that provided a little relief could help.

Emphasys execs sought and received a follow up meeting with the FDA where they suggested slicing the data differently. But the company received no word until last week when the FDA sent a letter saying it would consider a “confirmatory trial,” with no details on what that required.

That last bit of uncertainty spooked Emphasys’ investors. Just negotiating the new trial would take six months and Emphasys was out of money. The company had been counting on good news from the FDA to help it to another round. All together, the investors had poured $75 million into the company. That’s on top of $15 million debt the company took on after pulling an IPO attempt in 2008.

McCutcheon, who says he's buried in emails from disappointed patients and pulmonologists, hopes a corporate buyer will have the muscle and stomach to push for approval. The company laid off 50 of its 55 employees.

Clearly, the current economic conditions didn’t help. And many of Emphasys’ investors have been with the company since its 2000 start, so the well was likely running dry. But McCutcheon says the FDA, not the economy, is to blame. His primary complaint is inconsistency. He says the agency shouldn't move regulatory goal lines on device companies. Of his device executive brethren, McCutcheon says, "We're more worried about the trends at the FDA than we are about the economy.”

Read more in our upcoming START-UP magazine.


"Pie chart" from flickr user by net_efekt used under a creative commons license.

Can't Keep Quiet About This

Perhaps lost in the headlines about Emphasys Medical Inc. filing to raise up to $86.3 million in an IPO is the important fact that this company, the leader in the race to develop the first interventional treatment for emphysema, this month submitted the results of VENT, its 321-patient pivotal trial, to the Food and Drug Administration.

It’s all there in the S-1.

VENT, which stands for Bronchial Valve for Emphysema PalliatioN Trial, was a randomized clinical trial conducted at 31 centers in U.S. Its goal was to demonstrate the clinical benefits and safety of the Emphasys Bronchial Valve.

According to Emphasys’ S-1, the treatment group got EBV treatment in one lung along with optimal medical management including pulmonary rehabilitation. The control group received only optimal medical management treatment and pulmonary rehabilitation.

The endpoints were (drawing from the S-1):

Physiologic Improvement: FEV1, a co-primary endpoint of the study, measures the volume of air forcefully exhaled by a patient over time.

Exercise Tolerance: A patient’s exercise tolerance is used as a proxy for the patient’s ability to function on a daily basis. VENT used two tests of exercise tolerance. A co-primary endpoint of the study was 6MWT, which measures the distance a patient can walk in six minutes. Cycle ergometry, one of the secondary endpoints in VENT, measures the maximum workload exerted by a patient on a stationary bicycle.

Quality of Life: VENT used a standard, pulmonary-disease-specific questionnaire called the St. George’s Respiratory Questionnaire, or SGRQ, as a secondary endpoint in the study. Patients answered questions related to frequency and severity of symptoms, activities that cause or are limited by breathlessness, the impact the disease has on social functioning and any attendant psychological disturbances resulting from the disease.

Breathlessness: VENT used a standard questionnaire called the modified Medical Research Council Dyspnea Scale, or mMRC, as a secondary endpoint. The mMRC asked patients to report on when they experience breathlessness and what causes it.

Oxygen Consumption. Many patients utilize supplemental oxygen to reduce breathlessness. In the VENT trial, patients reported how much oxygen they consumed on a daily basis.

And the results, according to the S-1, are……:

The patients treated with the EBV in the VENT study demonstrated statistically significant improvements, measured by meeting a p-value equal to or less than 0.025, in both of the co-primary efficacy endpoints, FEV1 and 6MWT, as well as in three of the four secondary endpoints.

FEV1 showed a 6.4% difference relative to the control at a p-value of 0.0047, and the 6MWT demonstrated 5.6% improvement relative to the control at a p-value of 0.0073. We demonstrated improvement in all four secondary endpoints, with the improvement in three of these endpoints, cycle ergometry, quality of life and breathlessness, meeting the hurdle for statistical significance.

As for safety, the primary safety endpoint was a major complications composite at 180 days. The composite included death, respiratory failure, pneumonia distal to the valves, massive hemotysis, prolonged pneumothoraces and empyema.

At the six-month follow-up, the treatment arm MCC rate was 5.9% compared to 1.0% for the control arm, and from six months to one year, the treatment arm MCC rate was 4.5% compared to 4.0% for the control arm.

There's plenty more in there so we encourage you to take a look.

The IN VIVO blog didn't even try to reach Emphasys executives or investors for comment. It is, after all, quiet period time. But the action of filing for an IPO without having heard from the FDA says enough about their confidence in the results. It'll be interesting to see whether final word from the FDA will be needed for this IPO to happen.

But a happy ending to both sagas will be good news for patients, interventional pulmonologists and investors in companies developing devices to treat lung disease. IN VIVO, the magazine, will be profiling another significant player in this area, Asthmatx Inc., in our next issue.