Medical Device Daily Associate Managing Editor

While much of the focus thus far in evaluating the connection between refractory migraines and patent foramen ovales (PFOs) has been concentrated on a few companies – including NMT Medical (Boston), AGA Medical (Golden Valley, Minnesota) and St. Jude Medical (St. Paul, Minnesota) – that are developing permanent implantable device technology to close the common heart defect, a few companies are quietly working on a minimally invasive treatment for the condition in which no device is left behind after the surgery.

A PFO is a hole in the wall between the two upper heart chambers that fails to close after birth.

One player exploring this new no-device-left-behind approach for PFOs is privately-held Cierra (Redwood City, California), via its PFx Closure System, which was conceptualized and initially funded by the well-known medical device incubator, The Foundry (also Redwood City), beginning back in January 2003.

At the time of Cierra's genesis, according to Erik Engelson, president and CEO, it was decided that the company initially would go for an approval in the refractory migraine market rather than the stroke market, which was what PFO closure devices were first designed to treat.

“The Foundry identified PFO as an opportunity,” Engelson told Medical Device Daily, and after looking at the stroke opportunity for PFOs, “decided that was a long clinical study and the two companies in that, NMT and AGA, had been having trouble enrolling patients.”

It was decided that migraine was a better business model for the company, especially since “some of the retrospective work in migraines looked very compelling.”

Indeed, there are an estimated 2.2 million migraine sufferers with PFO and aura in the U.S., and retrospective studies have shown that closing a PFO can reduce migraine attacks. Of that number, an estimated 750,000 could possibly benefit from PFO closure, resulting in a market potential of nearly $3 billion in the U.S. alone.

The procedure, like those done by other players in the treatment of PFO that leave an implant behind, is performed by an interventional cardiologist in the catheterization lab. During the procedure, a guidewire is introduced via the right femoral vein to cross the PFO for balloon sizing and device placement. Next, the company's PFx catheter is advanced into the right atrium over the guidewire and once the device is in place, suction is introduced to tightly close the PFO and hold the PFO tissue against the inside of the device. Radio frequency (RF) energy then is applied to the suctioned area to “weld” the tissues of the PFO closed, with the entire procedure taking about thirty minutes to complete.

Most patients are released from the hospital after a day, according to Engelson.

Not having an implant in the body after surgery presents several advantages, he said. Some adverse events that he said are associated with implants include atrial fibrillation, which is reported in up to 12% of cases. Additionally, he noted that heart palpitations have been reported in up to 65% of patients and there also is the very real threat of thromboembolic issues.

Cierra said it expects to get its CE mark for the system sometime this year. As for the U.S., the company hopes to begin an investigational device exemption study for migraine sometime in the first half of 2007 but does not expect a U.S. approval until about 2010.

Thus far, Engelson said Cierra has trial data out to 14 months, and up to this point the PFO closure with the PFx system appears to be durable. He said that the company has had “zero” patient safety issues up to this point after enrolling 55 patients.

“We're really encouraged by that because we had to break new ground by exposing the substance of the heart to RF,” he said.

While the company has been at the forefront of the device-free PFO procedure movement, it is by no means alone. Another company, CoAptus Medical (Redmond, Washington), is working on an approach that also incorporates RF energy to close the PFO. That company has been financed by medical giant Boston Scientific (Natick, Massachusetts).

Additionally, NMT Medical, which already is heavily involved on the implant side for PFO closure, has trials under way in Europe for a bioabsorbable septal closure device called the Biostar

NMT has said that the Biostar is the first implant in a series of new, advanced septal closure technologies designed to provide a bioabsorbable option for patients with heart defects like PFO.

The company has thus far undergone three rounds of financing, including the most recent Series C that added $21 million to its coffers in June 2005.

That last round, Engelson said, should keep Cierra funded through the summer of 2007, although he said the company would probably raise another private round earlier that year to finish U.S. trials.