FDA Approves Cyberonics VNS Device for Treatment-Resistant Depression

Cyberonics CEO Cummins: Success at last.

Following a protracted and at times contentious product review process, Cyberonics Inc. (Houston) last month received notification from FDA that the company had received final approval to market its Vagus Nerve Stimulation (VNS) device for treatment-resistant depression (TRD). The VNS device was actually approved for TRD in February, but FDA stipulated that the device could not be marketed for that indication until the company had addressed agency concerns about its manufacturing operations, product labeling, and other issues.

Last December, Cyberonics received an FDA warning letter regarding “nonconformities with current good manufacturing practice (CGMP) requirements of the quality system regulation for medical devices.” Following a series of corrective actions and improvements in the company’s reporting systems, Cyberonics was notified by FDA in April that it was in full compliance with all quality systems and that the issues raised in the warning letter were fully resolved.

The April-to-July delay in granting final approval of the VNS for TRD is believed to be due, in part, to an investigation begun in May by the Senate finance committee. Although the finance committee has never publicly disclosed the focus of the investigation, with which Cyberonics has said it is cooperating, it is believed to center on the actions of FDA and the company during the device approval process. Following announcement of FDA’s decision to approve the VNS device for TRD, a spokesperson for the finance committee said that its investigation was still open.

FDA’s approval enables Cyberonics to position its device as a treatment for severe depression. According to the National Institute of Mental Health, depressive disorder is one of the most prevalent and serious illnesses in the United States, affecting nearly 19 million people. Cyberonics estimates that 20% of depressed Americans—or approximately 4 million people—experience chronic or recurrent TRD that has failed to respond to multiple antidepressant treatments, including medication, psychotherapy, and, in some cases, electroconvulsive therapy. The agency’s approval requires Cyberonics to establish postmarket product surveillance systems, including patient registries, research studies, and dosing formularies regarding the amount and efficacy of the electrical shock administered by the device.

The VNS is a small pacemaker-like device, implanted in the chest, that sends preprogrammed, intermittent, mild electrical pulses to the brain through the vagus nerve in the neck. Cyberonics describes the VNS as “the first FDA-approved implantable device-based treatment for depression.”

The VNS device was first approved in 1997 for the treatment of epilepsy. Cyberonics began seeking to extend the device’s approved use to TRD in 2003. Although FDA’s neurological devices advisory panel recommended such action in June 2004, the agency rejected the application two months later. Cyberonics subsequently submitted a revised premarket approval (PMA) application with supplemental information addressing the agency’s specific concerns.

The VNS has been approved for TRD in Canada and Europe since 2001.

Commenting on FDA’s decision to approve the VNS device for TRD, Robert Cummins, CEO of Cyberonics, said, “Today for the first time, Americans with treatment-resistant depression have an FDA-approved, informatively labeled, long-term treatment option for their lifelong and life-threatening illness.” Cummins speculated that the brain and neuromodulation will be the next frontier for medical devices, and will attract extensive research and product-development activities similar to those now being devoted to the heart and cardiac-rhythm management.

In granting approval, FDA continued to caution that the VNS device is not intended as a first-line treatment for depression, but is indicated for use only with those patients for whom more-traditional therapies have proven ineffective. The device is also not intended for individuals under the age of 18.

Lurie: A new low for FDA.

Approval of the device is not without controversy among some patient-advocate groups, most notably Public Citizen (Washington, DC), an organization founded by consumer activist Ralph Nader. His concerns about how the device was approved are believed to have been the catalyst for the Senate finance committee’s investigation. Commenting on the approval, Peter Lurie, MD, MPH, of Public Citizen’s health research group, said, “It’s a new low for FDA device approvals. If this device can get approved with data as unconvincing as these, it’s hard to see what can’t get approved.”

Hargis: Support for 2-in-1 potential.

But not all such advocacy organizations opposed the approval. Citing the “potential 2-in-1 treatment for people with epilepsy,” Eric Hargis, president and CEO of the National Epilepsy Foundation (Washington, DC), said that depression affects more than a third of all individuals with epilepsy. “We are extremely pleased with FDA’s approval of VNS therapy as a long-term adjunctive treatment in chronic depression . . . which is greatly underdiagnosed in people with seizure disorders. The FDA decision offers a significant new treatment option for patients and families affected by these coexisting conditions.”

In a conference call following announcement of FDA approval, Cyberonics CEO Cummins said that the new indication offers “the potential to do $300 million in revenue in the first four quarters after launch.” The company has reportedly added 200 people to its sales force in expectation of the interest in and demand for the device. Considering the extent of depressive disease, most medtech analysts seem to believe that the VNS device has significant potential for market success.

Cyberonics reported sales of $103.4 million for the year ended April 29, 2005, a decrease of 6.6% from year-ago revenues of $110.7 million.