According to the American Stroke Association (ASA; Dallas), each year about 580,000 Americans suffer an ischemic stroke resulting from an obstruction within a blood vessel supplying blood to the brain. Generally, only 3%-5% of these patients arrive at a hospital within the three-hour time window required to receive IV drug therapy. Stroke is the No. 1 cause of disability and the No. 3 cause of death behind heart disease and cancer, killing more than 150,000 people per year in the U.S.

One young neurovascular-focused company is working to extend the time window available to patients suffering from acute ischemic stroke using a non-drug-based platform. Penumbra (San Leandro, California), a company focused on developing and manufacturing products to treat patients suffering from stroke and other neurovascular diseases, reported the completion of a stroke trial evaluating the Penumbra system in the revascularization of more than 100 patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease.

Currently there is only one FDA-approved treatment for an acute ischemic stroke: intravenous (IV) delivery of tissue plasminogen activator (t-PA) (Activase), which is a thrombolytic agent. The agent is designed to dissolve the blood clot that is blocking blood flow to the brain. IV t-PA is currently limited in use since it must be used within a three-hour window from the onset of the stroke and it appears to carry an increased risk of bleeding.

Adam Elsesser, the CEO, director and founder of Penumbra, told Medical Device Daily that “the primary endpoint of the study is the ability for our system to recanalize the occluded target vessels; and also to record the incidence of device-related and procedure-related serious events.” With data collection now complete, 510(k) submission to the FDA is expected this year with the results of the trial to be available in 2008.

The Penumbra system is a package of tools used by neurointerventional specialists to remove occlusions from the large vessels of the brain that are causing an acute ischemic stroke. It works on the proximal surface of the occlusion, thereby eliminating the need for navigation through or beyond the occlusion.

The first component of the system is a clot debulking and aspiration platform that allows soft clots to be gently aspirated out of the vessel. The second component includes a thrombus removal ring that allows hard or fibrous occlusions, such as from the heart, to be captured and extracted without the need to cross through the clot.

A total of 125 patients were enrolled in this single arm, prospective, independently monitored trial at 24 centers in the U.S. and Europe. Patient enrollment was completed on June 5, less than one year from the start of the trial, and the three-month follow-up period is now complete.

Patients could be enrolled in the trial if they arrived at the hospital within eight hours of stroke symptom onset and were ineligible for or refractory to IV tPA therapy, among other criteria.

Elsesser told MDD: “the big question will be the data and when that is organized. Exactly when we are able to do that will depend on the timing of getting it organized and what is the right form to do that. But, we’ll know that by the end of this year.”

Prior to this Penumbra stroke trial, a Phase I safety and feasibility trial was conducted at six international centers in Europe, treating 20 patients. All patients arrived at the hospital within eight hours of stroke symptom onset and were suffering from complete or near-complete occlusions of at least one large artery in the brain. Of these 20 patients in the Phase I trial, 100% (20/20) had complete or near-complete restoration of flow at the site of primary occlusion. And 42% (8/19) had a good clinical outcome as measured by functional independence or substantial improvement of stroke symptoms at 30 days.

The Penumbra system is CE marked and has been commercially available in Europe since June.

“The company was started approximately three years ago, and we’re pretty excited about it. Most of us [in the company] come from the neuroscience [neuro] community, having worked in companies that focus on neuro. We have a strong interest in neuro, specifically to see some breakthroughs in stroke, which has been a perplexing disease for people over the years, and still a huge unmet clinical need. So if we can make a little dent in that and help out in that way, it would be fantastic. Beyond that — it’s hard to imagine. We just want to make a little clinical improvement,” said Elsesser.

“The results of the Penumbra system Phase I trial were extremely encouraging,” said Wayne Clark, MD, professor of neurology at Oregon Health Sciences University (Portland) and director of the Oregon Stroke Center (Portland). “We look forward to seeing the outcome from the 125-patient pivotal trial on this promising new mechanical thrombectomy system from Penumbra.”