FDA has approved EnteroMedics Inc.’s Maestro Rechargeable System, a pacemaker-like device used to help obese patients control hunger cravings.

In making the decision the agency took into consideration patients’ willingness to accept higher potential risk of the device which failed to meet its co-primary endpoints in a pivotal study. It is the first approval to result from CDRH's pilot program to formally incorporate patient preference into risk-benefit determinations for obesity devices, and it is the first new obesity device approved by FDA since 2007.

The implanted neuromodulator device used in EnteroMedics’ VBLOC vagal blocking therapy stimulates the vagus nerve which regulates the digestive system and helps suppress hunger. FDA has approved the device for adults 18 and older with a body mass index (BMI) of at least 40 to 45 who have been unable to lose weight through a weight loss program within the past five years, or who have a body mass index of 35 to 45 with at least one other obesity-related condition, such as type 2 diabetes, high blood pressure or high cholesterol.

"By blocking signals along the nerves that connect the brain and stomach, VBLOC reduces feelings of hunger and promotes earlier feelings of fullness, which can help people with obesity reduce the number of calories consumed and promote safe, healthy and durable weight loss," said Scott Shikora, EnteroMedics' chief consulting medical officer.

“While this survey tool is specific to obesity treatment, a survey tool developed using the same methodology could be used across disease areas,” an FDA spokeswoman said.

Thumbs Up Despite Missing Endpoints

Maestro failed to show a 10 percent excess weight loss margin of superiority against a sham device in the company’s ReCharge clinical trial. It also failed to meet its co-primary endpoint of showing 20 percent excess weight loss in at least 55 percent of subjects and demonstrating 25 percent excess weight loss in 45 percent of subjects.

Despite the shortcomings, an FDA advisory panel voted six to two, with one abstention, that the benefits of the Maestro Rechargeable System outweighed its risks. (See [A#01140623004].)

A key safety concern raised by panelists was that patients implanted with the device would be unable to undergo MRIs since the device is not considered safe for use with MRI machines, also known as MRI-conditional. Some advisors even considered whether it was safe to explant just the neuroregulator portion of the product and to leave the leads in, risking that patients might forget they have them and undergo an MRI later in life.

While five panelists voted that they didn’t think the trial had proven sufficient efficacy, eight-to-one said they considered it sufficiently safe. In supporting the benefit-risk balance, the panel also approved of EnteroMedics’ suggestion that it conduct a five-year post-marketing study.

“In considering the benefits and risks of the device in its review of the Maestro Rechargeable System, the FDA considered the clinical study and the panel’s recommendations,” said the agency in its Jan. 14 statement. “Additionally, the agency looked at an FDA-sponsored survey relating to patient preferences of obesity devices that showed a group of patients would accept risks associated with this surgically implanted device for the amounts of weight loss expected to be provided by the device.”

EnteroMedics VBLOC vagal blocking therapy is delivered via the Maestro pacemaker-like device.

Photo: EnteroMedics Inc.

Patient Risk Survey

The survey of 650 obese patients, which was discussed during an FDA workshop in 2013, examined how much risk patients would be willing to accept in return for potentially effective weight-loss devices and found that indeed patients were willing to take on some significant risks to shed those pounds. Patient group representatives at the meeting emphasized people have clear ideas about their expectations for devices and the government’s role in approving them. (See Also see "FDA Validates Tool For Incorporating Patient Preferences In Regulatory Decisions" - Medtech Insight, 30 September, 2013..)

“Providing that context of harm is most important in patient communications,” said Kate Ryan, senior program coordinator with the National Women’s Health Network during the meeting.

FDA notes the survey is a “proof of principle” study on how patient preferences should be used to make regulatory decisions.

“While this survey tool is specific to obesity treatment, a survey tool developed using the same methodology could be used across disease areas,” said FDA spokeswoman Jennifer Haliski. “The FDA is not conducting a patient survey for any other diseases at the moment, but it may consider using a study conducted by a manufacturer or a patient group or other methods to elicit patients’ preferences to inform regulatory decision making for other devices in the future.”

She adds FDA believes patients and caregivers who live with a condition on a daily basis and use medical devices in their care should have a say when approving a product, and may have a different view than agency reviewers and the clinical community about striking the right risk-benefit balance.

“It may be appropriate to approve a device for a specific intended population if adequate evidence indicates that a subset of well-informed patients with that illness would accept the risks as weighed against the benefits of that device,” said Haliski. “We would require appropriate product labeling that clearly defined the patient sub-population and their benefit-risk preference in the Indications for Use section.”

Approval of EnteroMedics’ Maestro comes several years after an advisory panel supported CDRH’s proposal to use a sliding-scale approach to study and review devices aimed at treating obesity. The agency identified 11 categories of expected and unexpected adverse events and expected follow-up procedures that could be associated with obesity devices within one year of a procedure and proposed three risk levels, characterized by the proportion of patients that experience events in the different categories. (See Also see "FDA Proposes Sliding-Scale Paradigm For Obesity Device Trials" - Medtech Insight, 21 May, 2012..)

The new tools used to facilitate regulatory development of Maestro fit into CDRH's broader Patient Preference Initiative, including efforts to better quantify risk-benefit determinations. (See Also see "FDA Takes Initial Steps To Quantify Patient Opinion" - Medtech Insight, 28 May, 2012..)

Post-Approval Study

As part of its approval of Maestro, FDA heeded the recommendations of its advisory panel to require EnteroMedics to conduct a five year post-approval study that will enroll at least 100 users and collect data on weight loss, adverse events, surgical revisions and explants and changes in obesity-related conditions.

Adverse events reported during the clinical study included nausea, pain at the neuroregulator site, vomiting and surgical complications. The device is also contraindicated in patients with cirrhosis of the liver, portal hypertension, esophageal varices or an uncorrectable, clinically significant hiatal hernia; patients who may be required to undergo an MRI scan; patients at high risk for surgical complications; and patients who have a permanently implanted, electrical-powered medical device or gastrointestinal device or prosthesis such as pacemakers, implanted defibrillators and neurostimulators.

Maestro already has a CE mark in Europe and is listed on the Australian Register of Therapeutic Good. FDA notes it is the first device approved by the agency since it green-lighted Johnson & Johnson’s Realize adjustable gastric band in 2007. (See Also see "Underpenetrated U.S. Gastric Banding Market Has Room For Two" - Medtech Insight, 15 October, 2007..)

FDA Weighs Patients' Risk Tolerance in Approving Obesity Device

More from Regulation

More from Policy & Regulation