AGA Medical (Golden Valley, California) has joined the growing ranks of companies evaluating the benefit of patent foramen ovale (PFO) closure for the treatment of migraine, saying it has received conditional approval from the FDA to initiate a new study under an existing investigational device exemption to examine the possible connections between migraines and PFOs.

The Prospective Randomized investigation to Evaluate the incidence of headache reduction in subjects with Migraine and PFO Using the Amplatzer PFO Occluder compared to Medical Management (PREMIUM) trial is a prospective, randomized, two-arm, double blind multi-center trial in the U.S. to determine whether patients who undergo closure of a PFO with an Amplatzer device have a reduction in both the frequency and severity of migraine headaches.

AGA Medical said the study is expected to enroll about 400 patients at up to 30 medical centers, with enrollment expected to begin shortly.

John Barr, president and chief operating officer, told Cardiovascular Device Update that the study would evaluate patients with refractory migraine with and without aura (visual disturbance). The patients, he said, will be randomized on a 1-to-1 basis to receive either an Amplatzer-driven treatment or standard of care medical management

“The way it works is there is a neurologist and a cardiologist investigator at each site,” said Barr. The neurologist will remain blinded throughout the trial while the cardiologist isn’t blinded because he or she has to do the procedure.” The trial will involve use of a sham procedure for patients who do not receive the device treatment. Those patients will be anesthetized and kept on the operating table as long as the patients who receive the device. Additionally, the control patients will have a catheter inserted into their bodies just as the patients who receive the Amplatzer procedure. “Historically,” Barr said, “one of the biggest challenges in migraine trials is a fairly pronounced placebo affect, so you’ve got to do everything you can to make sure that people are unaware whether they have received or did not receive the device.” After the procedure or sham procedure has been performed, the study neurologists will follow all patients in the 12-month treatment phase

Another company involved in migraine trials with PFO technology is NMT Medical (Boston), considered the current market leader in the sector, whose StarFlex system is being evaluated in the MIST I trial. In October, the company also received FDA approval for an investigational device exemption (IDE) to initiate a pivotal PFO/migraine clinical study, dubbed MIST II, which has yet to begin enrollment.

Also involved in the PFO space is heavy hitter St. Jude Medical (St. Paul, Minnesota), which entered the fray with the Premere system that it acquired with its $74 million purchase of Velocimed (Maple Grove, Minnesota) last spring. This past August, the FDA granted the company an IDE to begin enrollment in the Effect of Septal Closure of Atrial PFO on Events of Migraine with Premere (ESCAPE) migraine trial, but no patients have yet been enrolled.

Cardia (Burnsville, Minnesota), with its Intrasept device, is enrolling patients in Europe in its Patent Foramen Ovale Closure to Reduce Migraine Attacks (FORMAT) trial.

If these devices prove to be successful in trials, they could become one of the biggest single opportunities in interventional cardiology. Currently, more than 28 million people in the U.S., about 11% of the population, suffer migraine headaches. Of that number, an estimated 2.2 million have a PFO with aura, and some analyst have pegged the market opportunity in the U.S. alone at nearly $3 billion. AGA said a similar study in Europe is pending approval to initiate enrollment at seven medical centers.

Cardica: 1st cardio-device firm with 2006 IPO

Cardiovascular products manufacturer Cardica (Redwood City, California) was the first pure device company to enter the initial public offering waters in 2006, in February pricing 3.5 million shares of its common stock at $10 per share. All of the common stock was offered by the company, and it granted underwriters a 30-day option to purchase up to another 525,000 shares to cover over-allotments, if any.

Cardica manufactures proprietary automated anastomotic systems used by surgeons to perform coronary artery bypass graft (CABG) surgery. The company’s first two products are the C-Port Distal Anastomosis System (C-Port) and the PAS-Port Proximal Anastomosis System (PAS-Port). The C-Port system was FDA 510(k)-cleared in November 2005 after receiving CE-marking in April 2004. The PAS-Port system is not yet FDA-approved, but has CE marking and market approval in Japan.

The company said that its products minimize trauma to both the graft and target vessel in coronary artery bypass grafting procedures, thus serving as alternatives to hand-done suture procedures. “Our C-Port system creates compliant anastomoses, which potentially allow the shape and size of the anastomisis to adapt to changes in blood flow and pressure,” the company says in its Securities and Exchange Commission filing. Cardica shares have begun trading on the Nasdaq under the symbol CRDC.

SynCardia marks profit milestones

Rodger Ford, CEO of SynCardia (Tucson, Arizona), maker of the only FDA-approved total artificial heart, last month at an investor meeting promised that the company will move from “life-saving science venture” to profitability this year. The company in late 2004 reached a major milestone in the artificial heart/heart assist sector with FDA approval of its CardioWest temporary Total Artificial Heart (TAH-t) for bridge-to-transplant, thus becoming the first company to win U.S. commercialization for a total artificial heart. Ford told investors that the five-year-old company would see sales of $14.9 million and profit of about $6 million this year.

A very advanced-stage version of the original 1980s-era Jarvik heart, the TAH-t is used to keep the patient alive until a donor heart is available. About 550 patients have received CardioWest hearts or earlier versions since 1985. Crucial to the growth promised by Ford is development of a more portable pneumatic “driver” to power the CardioWest TAH-t devices.

Unlike the AbioCor heart from Abiomed (Danvers, Massachusetts), which is totally implanted in the patient’s chest, the TAH-t is a pulsating biventricular device that replaces the patient’s left and right ventricles and is sewn to the patient’s remaining atria. By means of tubes back through the chest wall, the device is connected to a driver that provides pulsed pressurized air and enables device monitoring.

SynCardia has been hampered, however, by the availability of just 37 drivers inherited from Symbion, a predecessor company. These drivers, supplying power and air to the TAH-ts, are called “Big Blues” for their filing-cabinet size and blue exterior finish. “We can sell more hearts than we can drive,” Ford told Cardiovascular Device Update. But the lack of additional Big Blues has turned out to have a beneficial effect, forcing the company to focus on “the foundation we’ve laid over the last year to systematize the business,” he said.

He said Syncardia is in the process of adding two smaller drivers, one from Berlin Heart – a “recovery driver, not a primary driver” that the patient transfers to after two, three or four weeks on the larger driver” – and another driver that it licensed from Medos Medizintechnik (Stolberg, Germany) that will re-place a Big Blue. These alternate drivers have been submitted for CE-marking and the company plans to apply for FDA approval of the small primary driver – citing “equivalency” to its large driver – “in April or early May,” Ford said.