A successful medical device needs to bat two out of three requirements: fulfill an unmet need, be an effective treatment, and be a simple solution.
But not all of those criteria may be completely determined before the product launch, according to speakers at the 2015 AGA Tech Summit, which is sponsored by the AGA Center for GI Innovation and Technology.
Poor marketing strategy to clinicians and payers combined with 12-month follow-up data sank an apparently promising endoscopic treatment for gastroesophageal reflux disease (the ENTERYX procedure). It was effective but technically difficult, and it was intended for patients who were already responding to medical therapy.
Aortic valve replacement, however – seemingly a much more complicated procedure requiring cardiac bypass and tiny stitches – has not only survived but also thrived, with demonstrable success and constantly evolving iterations.
Why the disparity?
Learning from failure
The ENTERYX procedure involved the circumferential injection of polymer just above the pyloric sphincter – a permanent solution for thousands of GERD patients taking proton pump inhibitors. The polymer induced inflammation and encapsulation, effectively narrowing the gastroesophageal junction and preventing reflex.
“Our preclinical studies looked great,” said Rich Cohen, who handled the project for the Boston Scientific Corporation at the time. “We were approved by the Food and Drug Administration as a Class III medical device. Our pivotal randomized trial, conducted after approval, was very good; 70% of patients were able to get off their medication.”
ENTERYX was launched in 2003, said Mr. Cohen, who is now global director of market development for the endoscopy division of Boston Scientific. Almost 4,000 patients underwent the procedure, most with very good, very stable results.
But injection precision was critical; the polymer had to be deposited intramurally. Fluoroscopy was necessary to provide real-time feedback of the deposition location. Unfortunately, this safeguard didn’t work every time, he said.
“We had good results in the hands of experts, but it never translated down, despite our required training program,” Mr. Cohen said. There were reports of chest pain and dysphagia in treated patients, another patient experienced a partial reduction in renal function due to partial embolization. Two patients died (0.05%), both due to complications from aortoenteric fistula.
In 2005, FDA issued an advisory about the procedure, and Boston Scientific voluntarily recalled it, ending its use.
Such rare complications might possibly have been acceptable for a procedure that was successful for a hard-to-treat disorder with no alternative treatment, but patients who qualified for ENTERYX were already being treated successfully with PPIs, Mr. Cohen said.
“Any time you are treating something invasively that already has a successful alternative, it’s very difficult to sell. And when you do sell it, the bar for adverse events is very, very low.”
Even before the clinical events, ENTERYX was a marketing problem child. The first stumbling block was actually a sales issue, Mr. Cohen said. Because patients were already being medically managed, most primary care providers felt there was no need for surgical or endoscopic referral, at least partially damming the flow of interest.
Reimbursement was also an issue. “Our clinical data supporting safety and efficacy were not enough to sway decision makers. We ended up having to do a randomized controlled trial after we launched. If we had to do it over again, we would tie our approval trials to [Centers for Medicare & Medicaid Services] for coding, because without that you are really facing an uphill battle for something that treats a quality-of-life disease,” Mr. Cohen said.1
Getting premarket support from specialists is crucial. “We should have talked to physician societies before launching. Without that, it’s like pushing a boulder uphill and the minute you stop, you get run over. Even if you’ve got the best product in the world, it’s useless if patients never get treated.”
A look at success
Aortic valve replacement, on the other hand, is a perfect solution to a perfect market and clinical confluence.
Initiated in 1960, it’s grown exponentially to serve a huge global market, said Dr. Stanley Chetcuti, director of cardiac catheterization at the University of Michigan Hospital and Health System, Ann Arbor.
“The numbers with aortic stenosis are similar to the numbers with coronary artery disease – about 1.5 million in the U.S. Of these 25% are operable, meaning about 300,000 patients eligible for replacement each year. Unfortunately only about 80,000 get that surgery, but even with that small number, it’s an enormous need.”
And an enormous market as well.
Aortic stenosis is far from a quality-of-life disease. In fact, the prognosis without surgery is dismal, with less than a 30% 5-year survival if the stenosis is symptomatic. There’s no real alternative management, either.