Medical Device Daily Associate

CLEVELAND — As an interesting addition this year to its Innovation Summit, the Cleveland Clinic unveiled the first of what promises to be an annual “Top Ten” list of what it predicts as the most promising medical innovations in the coming year.

The 2007 list — which includes therapies for cancer, asthma, heart failure, age-related macular degeneration and vascular disease, including several medical devices — was complied by a panel of clinicians from the clinic who whittled the list from about 100 products to the final 10.

“The top 10 list is the result of a survey of dozens of Cleveland Clinic thought leaders offered to promote widespread discussion on innovation and new technology,” said Chris Coburn, executive director of CCF Innovations, the clinic’s technology commercialization arm.

Four major criteria had to be met in order for a technology to qualify. To receive consideration, a product had to have significant potential for short-term clinical impact; a high probability of success; be on the market or close to introduction; and sufficient supporting data.

Marc Penn, MD, PhD, chair of the clinic’s Bakken Heart Brain Institute , chaired the project and moderated the eight-person panel presenting the list.

And the picks, in reverse priority:

10)Convection-enhanced delivery (CED) of drugs — a system used to administer medication directly to the site where it is needed, without exposing the rest of the body to a drug’s effects.

According to Michael Vogelbaum, MD, PhD, a neurosurgeon at the clinic’s Brain Tumor Center and director for the Center for Translational Therapeutics , who presented the CED technology for the panel, CED allows a drug to cross the blood-brain barrier, the natural defense against toxins trying to get into the brain.

“It’s been estimated that more than 98% of potential neurotherapeutics are excluded by the blood-brain barrier,” Vogelbaum said. “Unfortunately, critical targets of drug therapy are most often behind a normal blood brain barrier.” CED’s major advantage, he said, is relying “on the blood-brain barrier to keep the drug in the brain rather than outside the brain.”

The treatment has been primarily used as a treatment for malignant brain tumors. Other neurological applications are also being explored, including for epilepsy, enzyme replacement therapy, stroke movement disorders and spinal cord injury.

9)Left Ventricular Assist System (LVAS) — the first implanted ventricular assist device (VAD) that senses when to increase or decrease blood flow rate. It is designed to take over most of the function of the left ventricle, the heart’s primary pumping chamber, and helps generate the force necessary to propel oxygen-rich blood throughout the body.

Nicholas Smedira, MD, surgical director of the clinic’s Kaufman Center for heart failure, noted that the most important function of the newest generation of these systems is the introduction of non-pulsatile devices with ceramic bearings. Some of these newer systems — which are made by companies including WorldHeart (Oakland, California), Thoratec (Pleasanton, California) and Ventracor (Sydney, Australia) — may last up to 12 years and have greatly reduced infection rates and so far have not shown the failures of their older, larger, pulsatile counterparts.

8)Targeted cancer therapies — second-generation, small-molecule tyrosine kinase inhibitors used to block or modulate disease and provide treatments for advanced cancers, such as renal cell carcinoma. Clear cell carcinoma is the most common type of kidney cancer, which represents 2% of all adult cancers.

7)Endografting — a minimally invasive repair technique traditionally used in cardiology and now being used to treat vascular disease, such as thoracic abdominal aneurysms.

Panel presenter Roy Greenberg, MD, a vascular surgeon, said that aortic aneurysms are found in 5% of the population over the age of 65 in the U.S., comprising the 13th leading cause of death.

He noted the lack of prospective randomized data, until recently, showing endovascular repair to be superior to traditional open surgical repair in low-risk patients. Now data is available that shows that to be the case, out to about four years.

Greenberg said he expects the device to lower mortality rates for complex aneurysms, but noted that adoption “requires that we break some barriers of conventional treatment of these patients, requiring cross-specialization in terms of imagining, surgery and interventional techniques.” He said the technology also will require “additional developments” for implanting into small vessels and various delivery system challenges.

The specific product referred to most likely was Medtronic ’s (Minneapolis) Talent system. The company reported the filing of the first module of the premarket approval application for the Talent in November 2005 (Medical Device Daily, Nov. 21, 2005). Other companies with technology in this field include W. L. Gore (Flagstaff, Arizona) and Cook (Bloomington, Indiana).

6) Ranibizumab — a drug therapy, brand-named Lucentis, inhibiting uncontrolled blood vessel formation in the eye, developed by Genentech (South San Francisco) and approved by the FDA this summer.

Lucentis was approved specifically for the treatment of neurovascular wet age-related macular degeneration, the leading cause of blindness in people older than 55.

5) Bronchial Thermoplasty (BT) — a therapy being developed solely by Asthmatx (Mountain View, California), used to ward off asthma attacks. BT involves the controlled application of heat in the lungs to improve pulmonary function and reduce asthma symptoms. The company has developed a catheter-based procedure that employs BT, via its Alair system, to deliver thermal energy to the airway walls to reduce the presence of airway smooth muscle, the tissue thought responsible for airway constriction and breathing difficulties.

“The existence of bronchial thermoplasty offers us a non-drug, a therapy with a ‘permanent’ therapy for asthma’,” said panel presenter Tom Gildea, MD, medical director for the clinic’s Center for Major Airway Disease. Underscoring the word “permanent,” Gildea referred to three-year data in animal studies showing “no reaccumulation of airway smooth muscles so far.”

Gildea noted that the smooth muscle layer is an evolutional vestige, much like the appendix, and in humans rather useless, but often becoming inflamed and restricting the airways.

4) OCT (optical coherence tomography) — a noninvasive imaging technology used in the treatment and diagnosis of eye diseases, such as diabetic retinotherapy and macular holes and glaucoma.

With the OCT technology, clinicians can now “actually image individual cells in the retina,” said Andrew Schachat, MD, vice chairman for clinical affairs at the clinic’s Cole Eye Institute . Though it is primarily being used in the retina, Schachat said it will ultimately be used in all areas of the eye.

3) Neurostimulation for Psychiatric disorders — such as deep brain stimulation (DBS), is emerging as a treatment option for millions of patients suffering treatment-resistant depression and treatment-resistant obsessive compulsive disorder (OCD).

Ali Rezai, MD, director of the Cleveland Clinic’s Center for Neurological Restoration and director of its Brain Neuromodulation Center, said these two mental disorders account for 15% of the disease burden in the U.S. “That’s more than all cancers combined.”

Companies involved in the neurostimulation space for these conditions include Medtronic, St. Jude Medical (St. Paul, Minnesota), Boston Scientific (Natick, Massachusetts), Northstar Neurosience (Seattle) and Cyberonics (Houston).

2) Designer Theraputics Using Selective Receptor Antagonists – used to block receptor activation leading to improved patient outcomes. Examples include therapeutics that block the peripheral side effects, such as constipation and nausea of opioid medications for pain; increased stress response to mediate eating and smoking; increased good cholesterol using niacin.

And — drum-roll here —No. 1) Cancer Vaccines — used to prevent the disease and treat patients more specifically according to cancer type.

One example of a cancer vaccine is the HPV vaccine developed to prevent cervical cancer cause by the human papillomaviruses.

Asked by Medical Device Daily what items he anticipates to see on next year’s top 10 list, Penn mentioned systems for transmitting brainwaves to computers — being undertaken by Cyberkinetics (Foxborough, Massachusetts), and RNA interference. Others barely missing the cut this year but possibly making the 2007 roster, he said, include electronic medical records and telemedicine.