By KAREN YOUNG
CDU
And HOLLAND JOHNSON
CDU

The med-tech sector most likely to see the largest growth in the 21st Century perhaps may be neurological devices used to treat the most debilitating diseases — the traumatic after-effects of heart disease and stroke, Alzheimer’s and dementia and a variety of other neurological illnesses such as ALS and Parkinson’s. Among these technologies, reference the Activa Deep Brain Stimulation Device from Medtronic (Minneapolis) for Parkinson’s disease; the post-stroke therapy system from Northstar Neuroscience (Seattle); and the vagus nerve stimulation (VNS) technology from Cyberonics (Houston) for treatment of epilepsy and depression.

But as these systems are being developed for the brain, the cardiovascular sector is co-opting some of these technologies to treat heart disease.

Two key examples: Israeli company, BioControl Medical (Yehud), which is developing a neurostimulator technology used to zap the vagus nerve but targeting the heart, via implantation in both neck and chest; and St. Jude Medical (St. Paul, Minnesota), which earlier this month reported the first implant in a pilot study evalulating the ability to stimulate the nerves near the spinal cord to control angina chest pain.

BioControl’s device is the CardioFit, designed to improve heart function through the controlled stimulation of the vagus nerve. It cites preclinical and preliminary clinical data demonstrate that VNS has a therapeutic role in treating heart failure by reducing the heart rate and ventricular volumes in addition to restoring regular rhythm.

Ehud Cohen, CEO of BioControl, in emailed responses to questions from Cardiovascular Device Update, said the CardioFit system consists of “an electro-stimulator device with a nerve cuff electrode and an intra-cardiac electrogram (EGM) sensor.” It is considered a Class III device, which would require premarket application approval by the FDA.

By continuously monitoring the EGM signal, stimulation is adjusted to the patient’s heart rate,” Cohen wrote. “The vagus nerve is stimulated through a tri-polar cuff electrode that provides accurate control over specific nerve fibers, thus avoiding cross activation of undesired fibers.”

The device can be implanted quickly, with the electrode positioned around the vagus nerve in the neck, the device itself placed in a subcutaneous pocket in the chest.

Cohen wrote that the risks of implantation are similar to the risks of any surgery under general anesthesia, and the risks of having the implant remain in the body are similar to those of other implantable neurostimulators.

‘Significant probability for success’

“The CardioFit system is a novel therapy designed for a clinically unmet need,” said Cohen. “Of the existing neurostimulation device therapies currently in clinical development for cardiology indications, the CardioFit system is clearly the most advanced and has the most significant probability for success.”

Biocontrol says also that CardioFit has been found to provide significant benefit to the heart when used simultaneously with “other existing optimal medical therapies.”

The company is beginning an open-label pilot study of the CardioFit device, the primary endpoint being determination of the occurrence of adverse events resulting from the system and/or the implant procedure. Secondary endpoints include symptomatic, functional and structural status, as well as a review of biological serum markers. Investigators expect to enroll 20 to 30 patients, all between the ages of 18 and 75. Patients enrolled in the study will be followed for one year.

The trial is being conducted at various sin Europe, Israel and Australia, but BioControl promises to add sites in the U.S. once it is green-lighted by the FDA.

Dr. Paul Hauptman, director of heart failure, St. Louis University Hospital (St. Louis, Missouri), said, “I have closely followed the development of the CardioFit system and am hopeful that sites in the U.S. will soon join the clinical program and begin enrolling for this very important study.”

BioControl, which has 35 employees, was founded in 1999. In April 2006, American Medical Systems (Minnetonka, Minnesota) secured an exclusive license to BioControl’s technology for its miniaturo system to treat urge incontinence and interstitial cystitis. BioControl said it is using the funds from that transaction to support development of the CardioFit.

First-in-man launch of St. Jude’s Genesis

St. Jude in early March reported the first patient implant — though it was actually first-in-female — in a pilot study that will provide preliminary evaluation of the ability to stimulate the nerves near the spinal cord to control chronic angina chest pain.

A 53-year-old Massachusetts woman was the first to receive this investigational device, called the Genesis neurostimulation system. She is one of the 1.3 million Americans — as estimated by the American Heart Association (Dallas) — who suffer from painful chronic angina, with 75,000 new cases of treatment-resistant angina each year.

The Genesis system was developed by St. Jude’s neuromodulation division, Advanced Neuromodulation Systems (ANS; Plano, Texas), which recently received FDA clearance of tripolar leads for use on its Renew system to treat neuropathic low back pain.

Implant of the Genesis “went smoothly,” said Thomas Simopoulos, MD, interventional pain specialist with the Arnold Pain Management Center at Beth Israel Deaconess Medical Center (New York), who performed the implant. “I am hopeful that spinal cord stimulation will offer a minimally invasive treatment option for patients with chronic, intractable angina.”

According to Rohan Hoare, VP of strategy and emerging therapies for ANS, spinal cord stimulation (SCS) for the treatment of angina has been used extensively in Europe “on the order of 15 to 20 years” and used in the U.S. for some time, but primarily in off-label applications.

Avoiding surgical complications

While it’s still too early to tell where SCS will ultimately fit within the angina treatment pantheon, data from the Electrical Stimulation Bypass Surgery (ESBY) trial — published in Circulation in 1998 — suggested that SCS may be a therapeutic alternative for patients with an increased risk of surgical complications and no prognostic benefit from surgery. In the ESBY trial, SCS was investigated as an alternative to coronary artery bypass grafting (CABG) in patients with no proven prognostic benefit from CABG and with an increased surgical risk.

The 104-patient study showed that CABG and SCS appeared to be equivalent methods in terms of symptom relief in this group of patients.

While Hoare said that the Genesis is primarily intended to alleviate the pain associated with an anginal attack, he noted that there is some evidence from the European literature that it may have some prophylactic benefit as well. “So that you not only alleviate the pain of an attack but you actually reduce the frequency of the attack, so you get a benefit two ways,” Hoare said.

The Genesis functions much like the Renew system used for back pain, with one distinctive difference: the Genesis uses an internal battery instead of relying on an external power source as the Renew does.

Hoare said that the Renew is very useful in situations where a larger power supply is needed for a treatment; however, the angina indication does not require as large an energy source, thus allowing the power supply to be completely internalized.