FDA Panel Mixed on Implanted Weight-Loss Device

Larry Hand

June 18, 2014

An advisory panel of the US Food and Drug Administration (FDA) issued a mixed recommendation yesterday on whether a first-of-its-kind implantable device should be approved for weight-loss treatment in severely obese individuals.

The Gastroenterology-Urology Devices Panel of the FDA's Medical Devices Advisory Committee voted 8 to 1 that the Maestro Rechargeable System vagal blocking therapy (VBLOC) is safe for use in patients as indicated, 4 to 5 that it is effective, and 6 to 2 with 1 abstention that its benefits outweigh its risks.

The Maestro system, from EnteroMedics of St. Paul, Minnesota, consists of a rechargeable neuroregulator device implanted into the lateral chest wall, with flexible leads placed laparoscopically around the vagus nerve. Electrical pulses act to suppress neural signals, thereby helping patients feel fuller and curb their appetites, according to the manufacturer.

The system also includes a mobile charger, a transmit coil, and an AC recharger, as well as a laptop computer loaded with clinician programmer software and a programmer cable. Clinicians can modify therapy parameters and schedules and can obtain diagnostic information through the programmer.

The system is indicated for obese adults with a body mass index (BMI) of at least 40 kg/m2 or of at least 35 in persons with at least 1 obesity-related comorbidity and who have failed at least 1 supervised weight-management program in the past 5 years.

Panel discussions centered around unmet endpoints, the generalizability of the trial results, the lack of long-term data, and the fact that the device is unsafe for patients who need magnetic resonance imaging, likening it to pacemakers in that regard.

Endpoints, Safety, and Data

Panel members who voted against the device’s effectiveness cited the lack of meeting coprimary endpoints in a pivotal clinical trial as a primary reason, although several panel members said the trial did show effectiveness anyway.

In the trial, called ReCharge, researchers found that average excess weight loss in patients randomly assigned to VBLOC came to 24.4% at 12 months compared with 15.9% for patients randomly assigned to sham implants, for a difference of 8.5%. The trial had a "super-superiority" coprimary endpoint, however, of a 10% difference.

Also, 52.5% of VBLOC patients had excess weight loss of at least 20% and 38.4% had excess weight loss of at least 25%. Those percentages fell short of coprimary effectiveness endpoints of at least 55% and 45%, respectively.

EnteroMedics spokespersons argued that the results showed the device to be effective even in the absence of meeting endpoints.

"This is exactly what we would expect from a weight-loss therapy," Scott Shikora, MD, chief consulting medical officer for EnteroMedics and section chief of bariatric surgery at Brigham and Women's Hospital in Boston, Massachusetts, told the panel members.

Maestro "can provide patients with a unique and effective treatment option," Caroline M. Apovian, MD, professor of medicine at Boston University School of Medicine and director of the Nutrition and Weight Management Center, at Boston Medical Center, said.

EnteroMedics spokespersons also presented evidence of safety for the device system. With a primary safety endpoint being 15% of serious adverse events (SAEs), the study came in at 3.7% SAEs, according to EnteroMedics.

FDA presenters, however, said the safety profile really came to 8.6% when SAEs related to treatment and surgery were included, although that still fell below the 15% mark.

During the public hearing portion of the meeting, 12 people, including patients who participated in the clinical trial, spoke in favor of recommending approval, while 1 person spoke against.

Ted Kyle, RPh, MBA, a pharmacist and chair of the Obesity Action Coalition, said the committee should not exact a new barrier to treatment because of an unprecedented standard of supersuperiority for this case. "This is a standard for which no precedent exists," he said.

Laurén A. Doamekpor, PhD, senior fellow with the National Center for Health Research, recommended against approval because of the unmet endpoints and because the clinical trial population did not represent the severe obesity population.

More than 80% of trial participants were women, and more than 92% were white. Mean age came to 47.1 years.

"It is unacceptable that there is so little diversity in the ReCharge trial," Doamekpor said, and committee members shouldn't draw any conclusions for black and Hispanic women or men.

Panel member Peter B. Imrey, PhD, from the Cleveland Clinic in Ohio, summed up the panel's dilemma. He praised EnteroMedics and FDA staff members for presentations in principal, but the data "unfortunately left us at sea," he said.

Panel member Karen L. Woods disclosed that she owns stock in a competing company; no other advisory committee members have disclosed any relevant financial interests.

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