Medical Device Daily Associate

While there certainly is excitement among patients, doctors and investors about the potential for patent foramen ovale (PFO) closure to cure refractory migraines, a prominent UK neurologist has cautioned against overexuberance on the treatment's potential prior to seeing more complete data.

In a Wednesday morning conference call sponsored by Prudential Securities (New York), Peter Goadsby, MD, said that until he sees compelling results from the UK-based MIST I (Migraine Intervention with STARflex Technology) and probably data from as-yet-to-be-enrolled U.S. trials, he would not personally consider referring any of his patients to cardiologists to have what he called an “invasive” procedure done.

The procedure involves closing the PFO, a septal heart defect in which a flap-like opening between the right and left atriums of the heart allows a right-to-left shunt of vs. blood flow between the two chambers.

Goadsby, a professor of clinical neurology at University College London, is considered one of the world's leading migraine specialists. He noted that migraines appear to be inherited disorders of the central nervous system and eliminating PFOs, one of many possible triggers for migraines, would most likely not cure the majority of patients, but it could help reduce the frequency of migraine episodes.

“Closing a PFO could never be curative,” he asserted, “but the idea that it might eliminate a potent trigger is another issue.”

The relationship between PFOs – which are present in roughly 25% of the general population at birth – and migraines is still not fully understood, but it has been found that roughly 20% of migraine sufferers with auras (visual disturbance) and about 40% to 50% of these patients have a PFO.

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.

Based on monetary numbers like that, it is no wonder that many companies are willing to take a chance on a technology that has not been fully proven by comprehensive studies.

One company involved in migraine trials with PFO technology is NMT Medical (Boston), 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.

Another competitor in the sector 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 (Medical Device Daily, April 8, 2005). 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.

Yet another competitor in the PFO field, AGA Medical (Golden Valley, Minnesota), whose lead product is the Amplatzer PFO Occluder device, does not yet have approval for a trial for the migraine indication.

Analysts have said that if the PFO closure could offer a significant reduction (50% to 70% partial-to-complete remission), it would be feasible for a significant percentage of potential patients to have their PFO closed.

Asked what he thought would be an acceptable threshold for partial remission of aural migraines, Goadsby said he believed that a 70% partial-to-complete response rate would be a good point to start talking about using a medical device that must be implanted in the heart vs. the standard 50% for a drug for the condition “that can be started or stopped.”

However, as he stressed throughout his presentation, patients must be made aware of the fact that this procedure most likely is not offering a cure, only the possibility of the reduction in the frequency of their migraines.

Another reason to be cautious, he said, was the disappointing results of the use of PFO closure systems to prevent ischemic strokes, which NMT and AGA had been investigating before the migraine opportunity presented itself.

It would seem more logical for these devices to work in stroke patients because theoretically, closing the PFO should ensure that blood does not travel between the two ventricles before being filtered by the lungs, thus preventing unfiltered blood carrying a clot from traveling to the brain and causing a stroke.

To be fair, the U.S. stroke studies from those two companies have had a difficult time enrolling because most prospective patients elected to have the PFO devices implanted under the auspices of a humanitarian device exemption instead of being randomized to the control arm of the trials.

While Goadsby said the migraine experience “doesn't give any comfort to the PFO study,” he was quick to point out that stroke and migraine are “separate diseases and separate physiologies, so if one worked and the other one didn't, I wouldn't collapse in horror.”

When the complete results of the MIST I trial come out, he said it would be important to separate out the complete responders from the partial responders to find out how many patients have regressed after the closure procedure.

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