It doesn’t take much time in a public location to realize that Americans are fat! In fact, the percentage of Americans who are obese (the medical term) has been increasing for several decades. Recent data suggest the trend is stabilizing, although it is not reversing.
We know that as weight increases, the risk to good health also increases in a whole variety of different ways. In fact, virtually any disease or condition you can think of is made worse, one way or another, by the mechanical and metabolic changes accompanying substantial weight gain. Medicine has taken numerous approaches to losing weight that include drugs (with some failing miserably because of adverse events), behavioral modification, surgical procedures, public policy (remember the soft drink limit in New York?) and—last but not least—medical devices.
The FDA has approved three devices for weight loss. Two of them, Lap-Band Gastric Banding System and Realize Gastric Band, work by physically restricting the ability for the stomach to contain food. The latest, the Enteromedics’ Maestro Rechargeable System, uses an entirely different approach that involves electrically stimulating the vagus nerve to “tell” the brain that the stomach is full. The implanted components of the Maestro system include the neuroregulator, which generates the electrical impulses and is implanted subcutaneously, typically on the side, just above the ribs; and the leads and electrodes, which are placed in contact with the vagus nerve just above the junction of the esophagus and the stomach. The lead and electrodes are similar to the leads and electrodes used in cardiac pacemakers.
The Maestro system stimulates the vagus nerve at the junction of the esophagus and stomach.
According to its FDA approval letter, the Maestro Rechargeable System is for adults who have a body mass index (BMI) of 40 to 45 or those with a BMI of 35 to 39.9 with one or more obesity-related comorbid conditions. Patients are also supposed to have failed at least one supervised weight management program within the past five years. Maestro is not the weight-loss answer for the average hefty American. Someone who is six feet tall would need to weigh almost 300 pounds to have a BMI of 40.
The Maestro system is contraindicated in patients with cirrhosis of the liver, portal hypertension, esophageal varices, and uncorrectable significant hiatal hernia. It’s also contraindicated for patients for whom MRI is planned or in patients who have had permanently implanted electrical-powered medical devices, such as pacemakers, implanted defibrillators, or neurostimulators.
The Maestro system was studied in a randomized, double-blind, sham-controlled trial in which 239 people were randomized in a 2:1 allocation to receive either the real device or a sham device. People in the sham group were implanted similarly but with a neuroregulator that dissipated charges into an electronic circuit within the device without leads.
The study used percent excess weight loss (EWL) as the main outcome measure. It’s a calculation of the amount of weight a person has lost as a percentage of their ideal weight.
Endpoints not met
In the intent-to-treat analysis, the vagal blocking (VBLOC) group achieved 24.4% EWL at 12 months compared with 15.9% of those in the sham group (the study design assumed that the sham group would achieve only a 5% EWL). The difference was less than the prespecified superiority goal (a difference of 10 percentage points), so the first coprimary efficacy endpoint was not met.
|Maestro system vs. sham implantation|
|12 months||25.8% EWL||16.9% EWL||8.9%|
|15 months||24.4% EWL||12.9% EWL||11.5%|
|18 months||23.5% EWL||10.1% EWL||13.4%|
Other pretrial goals were not met. In the VBLOC group, 52.5% of subjects reached 20% or greater EWL and 38.3% achieved 25% or greater EWL. But neither of these results met the performance goals of 55% and 45%, respectively. As with the primary endpoint, the sham group did fairly well on these measures, with 32.5% reaching the 20% EWL goal and 23.4% reaching 25% EWL.
In terms of safety, fewer than 4% of subjects in the VBLOC group had a therapy-related severe adverse event, needed implant revision, or had an implant “issue.” That result met the primary safety endpoint. Improvements in variety of the health risk factors associated with obesity, such as LDL cholesterol levels, were similar between the VBLOC group and the sham group.
Going by these results, the Maestro system wasn’t very impressive, yet the device was approved. Why? Partly because the FDA considering what happened in the months after the yearlong trial ended. The people in the sham group regained a signficant amount of weight compared with those in the VBLOC group, so efficacy, when measured later, show a greater difference in favor of the VBLOC group.
Managed care implications
The Maestro device poses a rather interesting conundrum for payers. On one hand, it is FDA approved and gives providers another way to treat truly serious, life-threatening obesity. On the other hand, the device did not meet the efficacy endpoint goals at 12 months, nor did it have a large effect on the risk factors associated with obesity. And it’s bound to be expensive; one news report put it at $15,000 per patient, although as this column went to press, Enteromedics hadn’t set a price.
Payers are likely to pay attention to the entire set of FDA documents in their coverage decisions for this device, not just the 18-month results that salvaged the application and eked out FDA approval. Should payers set an even higher bar for behavior change and lifestyle modification prior to approving payment? Will they provide better access to counseling for weight loss? Will they seek other tech solutions such as weight-loss apps or digital coaches?
These and other questions are constant reminders that Tomorrow’s Medicine is still looking for a solution to our country’s weight problem.