An endpoint miss in the pivotal US trial of EnteroMedics’ anti-obesity device has halved the Minnesota company’s share price, but has not deterred it from seeking US approval for its Maestro product. This might not be as bad an idea as it looks at first glance: EnteroMedics has been here before and last time came out battered but smiling.
A trial of the Maestro nerve-blocking technology in 2009 missed safety and efficacy endpoints, and demolished EnteroMedics’ share price by 80%. The company picked itself up and, while the shares did not recover, went on to secure European approval for the device. But in medtech the FDA has higher standards than the notoriously laissez-faire European regulator – and the advent of antiobesity drugs means it is by no means certain that Maestro would find a niche even if approval were assured.
The Maestro device is similar to a pacemaker in that it is implanted under the skin and uses wires to deliver electrical impulses. The wires, however, lead not to the heart but to the vagus nerve, which innervates the stomach and other parts of the digestive system. The device’s impulses block the nerve’s activity, making patients feel full earlier. EnteroMedics calls the process VBLOC therapy.
Results of the ReCharge trial were not a complete washout, despite the missed endpoints. Patients were implanted with either a functioning device or a device with no leads as a sham control. In the intent-to-treat population of 239 patients, those treated lost an 24.4% of their excess weight, compared with 15.9% for sham control patients.
This 8.5-point difference between the two ReCharge arms was statistically significant. The trial protocol, though, called for the VBLOC therapy to demonstrate “super-superiority” – an improvement of 10 points over the sham treatment – as the primary endpoint.
As a comparison, gastric bypass surgery patients can expect to lose around 70% of their excess body weight, or 28% of their overall body weight. As for the drugs, in clinical trials, placebo-adjusted overall weight loss with Vivus’s Qsymia was between 7.5 and 9.4% (Spotlight falls on Orexigen as Vivus jumps through FDA hoop, July 18, 2012).
EnteroMedics intends to press ahead with a premarket approval (PMA) filing in the second quarter, in the hope that the efficacy, combined with the very good safety data from the trial, will be sufficient for the FDA.
But it will have to work hard to show that VBLOC therapy deserves approval when it provides weight loss in the same range as anti-obesity drugs and far beneath that provided by bariatric surgery.
Even if approval is granted, the laparoscopic Maestro implantation procedure – while less invasive than bariatric surgery – costs around $20,000, so reimbursement will be necessary to build significant sales.
US launch will also be tricky to fund as little money is coming in from sales elsewhere. Analysts at Canaccord Genuity say that Maestro’s uptake in Europe has been slow owing to a deliberately cautious launch, because any complications or serious adverse events must be reported to the FDA as part of the US filing, and could have a negative effect on the US approval process.
As an innovative technology, Maestro will be subject to an FDA advisory panel meeting, which could be expected late this year or early next. That will be Enteromedics’ next challenge. Securing the approval itself will not be the last.
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