Medical Device Daily Contributing Writer

NEW ORLEANS — As balmy spring days bathed “The Big Easy” last week during the 33rd annual International Stroke Conference, sponsored by the American Stroke Association (ASA; Dallas), one could not help but think of the saying “hope springs eternal.”

Stroke, typically described as either excessive bleeding or inadequate blood flow in the brain, has proven to be one of the most, if not the most frustrating diseases for the healthcare community to treat successfully. It is especially frustrating because stroke is a huge medical problem, with roughly 700,000 events per year in the U.S., causing an estimated 150,000 deaths – after heart attack and cancer, the third most deadly disease.

The cost burden to the U.S. from stroke is enormous. According to the ASA, more than $62 billion was spent on stroke in 2007 in the U.S., about 32% for nursing home care, drugs, other medications and home healthcare. Additionally, stroke is a condition that has ongoing impact, not only on the stroke victims/survivors, but on all those around them.

Against this bleak backdrop, researchers, physicians and industry met here, hoping to learn about any encouraging developments made over the past year. While there were no blockbuster developments, glimmers of hope for better treatment modalities did appear.

Perhaps the most encouraging news came from privately-owned Penumbra (San Leandro, California), which reported superb results at a late-breaking clinical trial session from its recently completed acute ischemic stroke (AIS) trial. As previously reported, the company had received FDA 510(k) clearance at the beginning of the year (Medical Device Daily, Jan. 9, 2008).

The Penumbra system uses a microcatheter-based thrombus aspiration and debulking/removal device that offers a multi-modality approach to the revascularization of occlusions occurring in the intracranial circulation. There are three key advantages of its system: it works in the proximal position, meaning it does not have to be navigated through or beyond the occlusion; second, it provides continuous aspiration to remove clot debris and third, it has three different sized catheters, which serve different vessel sizes.

The company believes that not all clots are alike and that a single catheter will not always work. Its device not only can remove both soft thrombi and harder plaque with its continuous aspiration and built-in clot capture feature but it can remove blockages in smaller intracranial vessels.

Cameron McDougall, MD, chief of endovascular neurosurgery at the Barrow Neurological Institute (Phoenix) and a student participant, presented results from the single arm, prospective pivotal trial, which enrolled 125 patients at 24 centers in the U.S. and Europe. All patients in the trial had suffered an AIS, causing minimal or no blood flow, defined as TIMI blood flow of 0 or 1. After receiving treatment, an impressive 82% of the treated vessels were restored to near normal (TIMI score II) or normal blood flow (TIMI III).

McDougall noted that these patients experienced a significant improvement in their neurological status, as measured by the National Institutes of Health Stroke Scale (NIHSS). About 42% of the patients treated enjoyed a four point improvement in their NIHSS score at the 30 day follow-up point.

The incidence of serious adverse events was not significant.

McDougall said that “these results suggest that the Penumbra System may allow safe and effective revascularization in patients experiencing ischemic stroke secondary to large vessel occlusion.”

Penumbra has recently hired several sales reps and has launched the product into the domestic market.

It faces two competitors in the AIS market — Concentric Medical (Mountain View, California), with its Mechanical Embolus Removal in Cerebral Ischemia Retriever (Merci) device and Genentech’s (South San Francisco, California) drug compound tissue plasminogen activator (tPA).

The MERCI, initially FDA-approved in August 2004 for the treatment of acute ischemic stroke, is a catheter that contains a corkscrew-like wire that snares clots and then plucks them from the artery.

Whereas the Penumbra can treat smaller intracranial vessels, the MERCI is designed to restore blood flow only in large vessel. Based the published literature that was discussed in the company’s August 2007 S-1 filing with the SEC, between 30% and 50% of all ischemic strokes in the United States emanate in large vessels.

The results of Concentric’s first trial, dubbed MERCI, reported in the July 2005 issue of Stroke, revealed a relatively modest 46% recanalization rate, based on intention to treat. Concentric’s second trial, called Multi MERCI, was somewhat more effective, restoring blood flow in 55% of AIS patients,

According to its S-1 filing, which was prepared in anticipation of an initial public offering (IPO) in late 2007 or early 2008, Concentric has “no plans to conduct any additional clinical trials that may be essential for the medical community to endorse the adoption of our system.”

With the very difficult stock market conditions, Concentric recently abandoned its IPO aspirations and instead has raised money from private sources.

A critical advantage of these two device-based approaches to AIS over tPA, which still remains the gold standard, is that they are approved to treat patients for up to eight hours, Intravenous (IV) tPA is currently only FDA-approved for use up to three hours. This narrow “therapeutic window” in part explains why a paltry 3% of AIS victims are receiving IV tPA therapy. Intra-arterial tPA, delivered via a catheter threaded from the femoral artery into the brain, is often used up to six hours after the three hour tPA IV window has expired but this is not expressly approved by the FDA.

TPA can be delivered intravenously at virtually all hospital emergency room, whereas these two clot removal devices will require the considerable skills of an interventional neuroradiologist. MDD estimates that there are approximately 300 hospitals in the USA with active neuro-interventional programs.

The Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) Australian study, reported at a late breaking clinical trial session, tested the hypothesis in a randomized, double-blind, placebo-controlled trial that IV tPA could be used successfully up to six hours after an AIS event. Although the study was fairly small and missed its primary endpoint of showing that tPA could significantly reduce infarct size as measured by MRI, it demonstrated some meaningful benefits.

According to the lead author, Stephen Davis, MD, professor of neurology at the University of Melbourne (Melbourne, Australia) “tPA was associated with a significant restoration in blood flow and improved functional outcomes.” He said these results were encouraging enough to warrant a larger pivotal trial.