Medical Device Daily

Brain to stomach, brain to stomach, ALERT: food is on the way, start expanding.

Stomach to brain (as food is consumed): not satisfied yet, send more food.

This is essentially the conversation that takes place between a person's brain and stomach, usually from the minute the nose senses food. And this communication is the reason that EnteroMedics (St. Paul, Minnesota) has developed its alternative to weight-loss surgery: a technology designed to slow down or even block the signals from the brain to the stomach and back again.

EnteroMedics recently reported interim data from the VBLOC-RF2 feasibility study of its VBLOC vagal blocking therapy device, the Maestro. The study, taking place at two sites in Europe and one in Australia and including 38 implanted subjects, is designed to evaluate the system's safety and efficacy.

Follow-up data show excess weight loss of 37.6% in nine patients at 18 months of VBLOC therapy, 28.1% in 17 patients at 12 months of therapy and 17.9% in 35 patients at six months of therapy, according to the company. Also, no deaths or unanticipated adverse device events have been reported.

"VBLOC therapy is designed to produce weight loss, in part, by controlling the feelings that lead patients to fail at losing weight, including hunger and a lack of feeling full," said Mark Knudson, PhD, president/CEO of the company. "These results are an encouraging sign that significant weight loss, occurring over an extended period of time, can take place without the serious side effects and adverse lifestyle impact seen in other obesity procedures.

"We continue to look forward to releasing the results of our randomized pivotal trial in the second half this year."

VBLOC therapy is a high-frequency blocking technology, not a stimulation therapy as used by other companies in the neuromodulation space, Greg Lea, the company's senior VP and CFO, told Medical Device Daily.

Lea explained that surgeons use to routinely cut the vagus nerves near the stomach to treat ulcers, a procedure known as a vagotomy. When they did this they noticed right away that patients lost their appetite and started to lose weight, Lea said. So, in 2002, based on an analysis of the vagus nerve's control of food intake and processing, EnteroMedics was founded to develop a therapy to treat, primarily, obesity.

VBLOC therapy is delivered through leads implanted laparoscopically in the abdomen to intermittently block vagal nerve trunks. High-frequency, low-energy electrical impulses are delivered by an implantable system to block the messages conveyed through the vagal nerves. If desired, the VBLOC delivery system can be removed if, and previous studies in animals have indicated that it does not damage or permanently affect the vagal nerves (Medical Device Daily, July 1, 2008).

Like other weight-loss procedures, the benefit of losing weight is complemented by an improvement in co-morbidities so frequently associated with obesity, such as Type 2 diabetes and hypertension. But unlike the laparoscopic banding and gastric bypass procedures, the improvements in co-morbidities do not correspond to weight loss, Lea said. He said in many patients the minute the VBLOC therapy is applied, or soon thereafter, the patient's hypertension improves, as well as their diabetic condition.

"In our case, what we're seeing is that those conditions improve prior to weight loss ... it's very encouraging," he said.

The company reported the co-morbidity data earlier this month at the J. P. Morgan conference. And it also reported its 18-month follow-up data showing that weight loss is "very consistent" with what patients experience in banding procedures, with a "much better" safety profile, Lea said.

According to the data, 10 patients with diabetes showed a statistically significant reduction of 1.1 percentage points, from 8.2% at baseline to 7.1% at four weeks; and 15 patients with both systolic and diastolic hypertension, which was either untreated or controlled with drugs, showed statistically significant reductions of 13.9 mm Hg in systolic pressure and 10.7 mm Hg in diastolic pressure at four weeks. The improvements in blood pressure are maintained through six months, the company noted.

EnteroMedics' study outside the U.S. started out with 38 patients enrolled, but some patients elected to drop out, Lea said, because the company had to offer a procedure in laparoscopic banding or gastric bypass if they didn't like the VBLOC procedure.

"Many of them used our procedure to jump the queue, getting into our study and then six months later saying 'give me lap band'," he said. "So we had some fall out, but we still anticipate somewhere between 20 to 25 patients in the trial."

In addition to the VBLOC-RF2 study, the Maestro system is being used in the company's pivotal EMPOWER clinical trial, a randomized, prospective, double-blind, placebo-controlled study being conducted in the U.S. and Australia under an FDA Investigational Device Exemption. The trial was fully enrolled at 15 sites (13 in the U.S. and two in Australia) with 294 patients in September.

Lea said that one-third of the 294 patients in the trial have the device implanted but not turned on while two thirds have the device turned on. The study blind – which remains in place for 12 months after activation of therapy in the experimental arm – is expected to lift in the second half of this year, EnteroMedics noted.

Another company, GI Dynamics (Lexington, Massachusetts) also has a device designed to treat diabetes independently of weight loss.

In September the company reported data showing that patients with uncontrolled Type 2 diabetes treated with an EndoBarrier GI liner achieved "significant improvement" of glycemic control in a week as compared to a sham control (MDD, Sept. 19, 2008). Most importantly, the company said, the immediate improvement of glycemic control was independent of weight loss, suggesting a direct action on the study.

GI Dynamics' device is designed to mimic the effects of gastric bypass surgery on a patient's metabolism, also resulting in weight loss and remission of Type 2 diabetes The EndoBarrier, creates a mechanical bypass of the duodenum and proximal jejunum. It allows food to pass through the device, and allows bile and pancreatic enzymes to travel outside the liner, allowing bile and intestinal hormones to travel around the liner without touching the food until later in the gut (MDD, June 27, 2008).

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