Medical Device Daily Associate
Making good on a promise for an investigational device exemption (IDE) this quarter, Advanced Neuromodulation Systems (ANS; Plano, Texas) reported that it has received the regulatory green light to implant 136 patients at 12 sites to investigate the safety and efficacy of the ANS Libra Deep Brain Stimulation (DBS) system to treat Parkinson’s disease.
Less than a month ago, ANS reported it had received an IDE approval to implant 160 patients at 12 sites to investigate the safety and efficacy of the Libra DBS system to treat essential tremor (Medical Device Daily, March 23, 2005). During that announcement for ANS’s essential tremor IDE, the company also reported that it had submitted an IDE for Parkinson’s disease, and anticipated receiving an IDE for that application this quarter.
Estimates of the prevalence of these two conditions vary significantly, ANS said, but it is generally thought that about 5 million people in the U.S. alone suffer from essential tremor, and another 1.9 million suffer from Parkinson’s disease.
The specific purpose of ANS’s study for Parkinson’s disease, the company said, is to demonstrate the safety and efficacy of bilateral stimulation of the subthalamic nucleus (STN) when using the Libra system as an adjunctive treatment for reducing some of the symptoms of advanced, levodopa-responsive Parkinson’s disease that are not adequately controlled with medication.
The company said it has identified a number of sites for the clinical study and expects the first implants of the system to occur sometime this quarter.
“This approval represents another major milestone for ANS,” said company President and CEO Chris Chavez. “Less than a month ago, we announced FDA approval of our IDE application to investigate the use of our DBS system to treat essential tremor. With these two approvals, we have the opportunity to move into the deep brain stimulation arena, which presents numerous new growth opportunities for our platform technologies to address various neurological conditions.”
Chavez told Medical Device Daily that the company’s strategy is twofold. First, he said ANS will “continue to develop world-class neurostimulation products and systems and to focus those on the chronic pain market.”
Secondly, while he noted that the chronic pain market is currently ANS’ core business; the company “will also develop its platform technology to address the long and growing list of applications in the neuro space.”
Chavez said the company believes that the neuromodulation market as a whole “promises to become a multi-billion dollar, multi-indication segment of the medical device industry.” He also noted that the company is “aggressively investing” in both product development and clinical trials to leverage its platform technologies into emerging clinical applications for neuromodulation.
In addition to planned pivotal studies to treat migraine headaches, essential tremor and Parkinson’s disease, he said ANS is “systematically incubating such promising new indications” as depression, pelvic pain, obesity, tinnitus and traumatic brain injury.
The company has also recently acquired exclusive intellectual property rights to stimulate a specific target in the brain to treat obsessive compulsive disorder and hopes to initiate a pilot study soon to further evaluate safety and efficacy of that technology.
Chavez said that while the scope of ANS’s numerous clinical studies was ambitious, the company would not waste its resources on applications that it considered untenable “We’re going to be very focused and very efficient in implementing both pivotal studies and in implementing pilot studies to incubate promising opportunities and when we are comfortable and convinced that the results support moving forward to a pivotal [study], we will do that in due course.”
Last month, the company also reported what it termed as “promising results” in the use of DBS for the treatment of depression.
An independent research paper in the neuroscience journal Neuron reported “a striking and sustained remission of depression in four of six patients.” ANS acquired the exclusive rights to this intellectual property over a year ago, it said.
Despite the encouraging results reported in the Neuron article, there were noted limitations to this first study of deep brain stimulation for treatment-resistant depression. Sample size was small, follow-up was limited and no sham surgery or systematic placebo control arm was used. There also were limitations on identifying markers that might predict response. Differences in electrode targeting and placement may have also contributed to the observed response variance. The mechanisms of action of DBS are incompletely understood.
While the depression results and the latest IDE approval are encouraging, the company and some of its officers, including Chavez, are still entangled in various legal matters, including several lawsuits brought by disgruntled shareholders after the stock’s value took a dramatic tumble.
One complaint alleges that the company violated federal securities laws by issuing false or misleading public statements and that during the class period ANS was engaged in unethical marketing involving payment to “certain physicians” for implanting the company’s products in patients.
On Feb. 17, the company disclosed that it had received a subpoena from the inspector general in the Department of Health and Human Services, “requesting documents related to the company’s sales and marketing, reimbursement, Medicare and Medicaid billing, and certain other business practices.”
A similar class action was filed against ANS, Chavez and Executive Vice President-Finance F. Robert Merrill III, for the same period, making substantially the same charges. It alleges that ANS “paid certain physicians a $1,000 incentive for each device implanted in patients,” and that the company’s relationship with its physicians “was based upon improper payments and not growing market acceptance of its products.”
Additionally, the company is lagging behind its competitor Cyberonics (Houston) in getting an approval in the U.S. for the potentially lucrative depression indication. That company received an “approvable” letter from the FDA in February for use of its Vagus Nerve Stimulation system in the treatment of recurrent treatment-resistant depression.
ANS had attempted to buy Cyberonics in the wake of that company’s August 2004 rejection by the FDA of use of the VNS system for treatment of TRD, buying just under 15% of the company’s shares. However, Cyberonics repeatedly rejected its rival’s advances, and ANS finally withdrew the offer last October.