Medical Device Daily Associate

ATLANTA – The picture provided by NMT Medical 's (Boston) MIST (Migraine Intervention with STARflex Technology) trial – the results of which were presented Monday during the annual meeting of the American College of Cardiology (ACC; Bethesda, Maryland) at the World Congress Center – can best be described as incomplete.

The trial was designed to see whether repairing the patent foramen ovale (PFO), a hole in the wall between the two upper heart chambers that fails to close after birth, can relieve migraine headache pain.

While on one hand the study showed that closing the PFO with an implant relieves migraine pain in some patients, the trial missed its primary endpoint of total elimination of headache, perhaps too lofty a goal for this, the first prospective, randomized, double-blinded study to examine the relationship between the implant and the condition.

Indeed, the height of that goal was a source of questions by several attendees reacting to the presentation.

Co-lead investigators Peter Wilmshurst, MD, a consultant cardiologist at the Royal Shrewsbury Hospital (Shrewsbury, UK), and Andrew Dowson, director of the King's Headache Service, Kings College Hospital (London), jointly presented the results of the MIST trial on Monday.

They reported that the 147-patient UK-based study of NMT's Starflex implant reduced migraine burden by about 37%, compared with about 17% in patients undergoing a surgical sham – that is, a procedure with no implant. The results were significant, but fell short of the trial's goal of a 40% improvement.

Dowson said that the number of patients who reported a 50% reduction in the total number of headache days – 42% of the Starflex patients and 23% of the sham patients – was statistically significant and compared favorably to numbers that would be expected in a trial for a migraine medication.

While NMT president and CEO John Ahern was disappointed that the study did not hit its primary endpoint, he expressed hope that future MIST studies would benefit from this early trial and serve as a building block towards an ultimate FDA approval.

“Although we were disappointed that MIST did not satisfy its endpoints, the study was designed to help demonstrate clinical relevancy and not to obtain a specific regulatory approval,“ Ahern said in a company statement. “The study has provided us with significant data that we intend to incorporate into our MIST II and MIST III studies.“

In a conference call after the MIST presentation, Ahern said the company is in the process of identifying elements of the trial that it can take to the FDA to help make any relevant changes to the MIST II trial, currently enrolling 600 patients, “so that it's a more robust study with a higher chance of success.“

Dowson added another tantalizing fragment to the still incomplete puzzle during the conference call when he pointed to another interesting trend in the MIST data, a trend towards better outcomes for the Starflex patients, particularly after they stopped taking aspirin and clopidogrel, about a month after the procedure.

“What in fact happened is that the aspirin and clopidogrel could actually have overlapped slightly into the observation phase,“ he said, adding that this prophylactic medication wash-out period could have acted as a “sort of confounding factor between the two groups for a part of that first month.“

Dowson said he and the other investigators need to drill down further with the data that they have, and noted that more data from the trial is expected to be available at the American Academy of Neurology (St. Paul, Minnesota) annual meeting next month in San Diego.

While the image may not be complete, at least one piece does appear to be consistent: The study found that out of 432 migraine-with-aura patients initially screened for the trial, more than 60% had a right to left shunt. A shunt is a heart defect, which allows blood to cross from the right to left chambers of the heart, bypassing the lungs. Of those patients, almost 40% had a moderate or large PFO, six times greater than the general population.

The PFO, which is present in developing fetuses to allow blood to circulate without being diverted to the lungs, allows unfiltered venous blood to enter the arterial blood circulation. The unfiltered blood may contain elements that can trigger migraines in some patients, researchers believe.

While a trial that does not supply all the answers may be intriguing to academia, question-averse Wall Street made the company's stock pay the price. Its shares fell more than 32% ($6.88) to close at $14.04, a new four-month low.

Prudential (New York) financial analyst Lawrence Biegelsen wrote in a research note that lack of discussion of safety data in the PFO arm of the trial could be a cause for concern.

“Safety was given short shrift during the presentation in our view, and this may be a key obstacle to acceptance by neurologists,“ Biegelsen said.