Medical Device Daily Contributing Writer

SAN FRANCISCO — The annual JP Morgan Healthcare conference, held here last week, covered a broad variety of topics and featured companies from both the public and private sectors. The usual mainstream med-tech topics such as drug-eluting stents, joint replacement and implantable defibrillators were prominently featured, but niche markets such as the treatment of patent foramen ovale (PFO) and other congenital heart defects that are gaining notoriety in the medical device space, sparked interest as well.

Publicly traded NMT Medical (Boston) is the best-known company in this arena, having pioneered this segment and still owning the lion's share of the market worldwide. The company recently stated that more than 15,000 PFOs have been closed globally with its pair of PFO closure devices, CardioSEAL and STARflex.

A PFO is an incomplete closure of the atrial membrane of the heart and has been implicated, although not conclusively proven, to cause various neurological disorders such as stroke or migraine headaches. Awareness of its potential role in these disorders has dramatically increased in recent years.

Speaking last Thursday afternoon near the close of the conference, NMT Medical's CEO, John Ahern, recalled a conversation in 2001 with a prominent interventional cardiologist who asked Ahern “what's a PFO and what does it have to do with me?“ Now, a little over three years later as the awareness of PFOs has surged, Ahern said this same physician recently exclaimed: “Wow, this could be bigger than the drug-eluting stent market!“

In these intervening three-plus years, NMT has initiated the 1,600 patient CLOSURE 1 trial, which compares the benefits of device-based PFO closure with traditional medical management for patients that have suffered an embolic stroke and have been found to have a PFO. As reported by the company in a conference call this past November, enrollment for this trial has been sluggish and very disappointing, suggesting that it will be several years before the trial is completely enrolled and the results are available.

The company's main rival in the PFO market, privately held AGA Medical (Golden Valley, Minnesota), also has suffered the same difficulty, as enrollment for its 500-patient RESPECT trial also has lagged badly.

As disclosed last fall (Medical Device Daily, Nov. 9, 2004), NMT received approval in the UK for the Migraine Intervention with STARflex Technology (MIST) study. MIST is a prospective, randomized, double-blind study enrolling migraine patients with a PFO to either PFO closure with the STARflex implant or to a sham procedure. The primary endpoint of the study is to compare the incidence of migraine attacks in patients with the most serious migraine headaches who have failed all conventional medical management.

This new indication represents a potentially huge new application for PFO closure technology. Moreover, results could be forthcoming quickly, as fewer than 200 patients will be enrolled (50% in each arm) and follow-up will be for only six months.

As recently noted (Medical Device Daily, Jan. 10, 2005), NMT Medical has announced that patient recruitment for MIST has progressed more quickly than originally anticipated, and full enrollment could be achieved in 3Q05, one quarter ahead of the initial year-end target. At the JP Morgan conference, Ahern said that he has been “pleasantly surprised“ by the huge interest in the trial and expressed optimism about its results. He cited the strong support of the Migraine Action Association, a migraine headache advocacy group representing more than 14,000 members in the UK.

In the critical U.S. market, the company will be meeting with FDA officials in the next few weeks and hopes to begin a domestic trial sometime in the second half of this year.

In addition to representing a “more immediate“ revenue opportunity, Ahern noted that the migraine opportunity is enormous. For example, of the 30 million estimated migraine sufferers in the U.S., roughly 20% are considered to be in the most serious category. About half of these are refractory to medical management and about half of those are likely to have a PFO. This leads to a target market of about 1.5 million patients. The international market adds another 2.3 million potential patients.

With a selling price for each PFO closure device of about $5,000, NMT's migraine opportunity alone is a multibillion-dollar one. Coupled with stroke opportunity, which he described as more than 600,000 patients annually worldwide, Ahern strongly believes that his company has major growth ahead.

In support of that assertion, he provided a model showing NMT's worldwide revenue growing from about $20 million in 2005 to more than $200 million in 2008. The migraine indication is expected to account for the majority of its growth, as stroke revenue will be constrained by the lack of a U.S. approval until at least 2009.

On Monday, three separate articles appeared in the UK press (The London Telegraph, The Scotsman and The Guardian) discussing the MIST trial. Dr. Andrew Dowson, director of the Headache Service at King's College Hospital (London) and co-primary investigator, said that “while many treatments help to control symptoms, as yet there is no cure for migraine. If the trial supports our theories about a migraine attack, it could be the most significant development in treatment for more than a decade.“

Another PFO contender is lesser known, privately held Velocimed (Minneapolis). Speaking last Wednesday afternoon to a large crowd of attendees at the Westin St. Francis, CEO Dennis Wahr, MD, formerly an interventional cardiologist, also indicated tremendous enthusiasm for the PFO market, describing it as a “staggering opportunity“ at $800 million and with a paltry 4% current penetration rate.

The company recently received the CE mark for its innovative Premere PFO closure system and will shortly begin marketing in Europe with a small, dedicated direct sales force. Wahr described Premere, which consists of two flexible, low-profile, nitinol anchors connected via an adjustable length polyester tether, as a revolutionary device “designed specifically and exclusively to close PFOs.“

Discussing its plans in the important U.S. market, Wahr said that he hopes to begin a stroke trial by mid-2005. Given that both NMT and AGA have had so much difficulty in recruiting patients, Wahr was asked how his trial could attain speedy enrollment. He told MDD that he has an “innovative but highly confidential“ trial design that could enable Velocimed to complete the stroke trial expeditiously.

Regarding a migraine/PFO trial, Wahr told MDD that he is “seriously interested“ in this market opportunity and hopes to begin a trial sometime in the future. He went on to say that “everyone will be watching the MIST trial with great interest“ and that his sense is that there will be benefit for a subset of patients.

In addition to discussing Velocimed's PFO activities, Wahr noted that its major revenue in the next few years will be derived from its Proxis embolic protection device, which he claims is the only such device to treat distal lesions and protect during initial crossing as well as protect the side branches. Proxis is CE-mark approved and Wahr hopes it will attain FDA approval before the end of 2005 for saphenous vein graft procedures.

To date, Velocimed has raised about $46 million from a group of highly respected venture capitalists and is supported by an experienced board of directors.

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