Medical Device Daily National Editor

Many millions who breathe without trouble during the day have, during sleep, continual breathing interruptions that prevent a full, good night's rest. As a result of airway blockage, they stop breathing for several seconds, then abruptly begin again, the constant irregularities preventing deep sleep and often waking them completely.

Obstructive sleep apnea (OAS) has consequences ranging far beyond the general side effects of sleep deprivation: it is frequently linked to other health complications, most often cardiovascular disease or even fatal stroke or heart attack.

And just as the heart beats in a regular pattern, breathing has the same sort of regularity – thus suggesting the potential benefits of a therapy long used to maintain a normal heartbeat: the pacemaker.

That is the technology strategy originally pursued by device titan Medtronic (Minneapolis), then spinning it off into Inspire Medical Systems (also Minneapolis), which now is pushing the Inspire II system – the II indicating the second-generation version of Medtronic's initial device – to commercialization.

Inspire last week reported launch of a small feasibility trial of the device, pacemaker-like in implantation and operation, essentially reviving the technology.

"It's not that they weren't interested," said Tim Herbert, CEO of Inspire, who was with Medtronic and so is completely familiar with the technology's initial development. But, he added, "We realized at Medtronic that we had so many ideas, but you just can't invest in all of them." And the device titan had not identified sleep therapy as a priority, he told Medical Device Daily.

Once implanted, the system delivers a low dose of electricity to the hypoglossal nerve to regulate the muscles of the upper airway, so as to produce normal breathing.

Medtronic had completed pre-clinical work and clinical testing of the initial device in a small feasibility trial enrollment, but decided that a spin-off would produce the more aggressive focus needed to take the device to commercialization. With Herbert, former vice chairman of Medtronic, agreeing to be head wrangler to take the updated version of the technology to commercialization, Inspire raised about $6 million, and Medtronic remained interested as a minority investor and holder of a seat on the company's board.

Herbert told MDD that the Inspire II is being positioned as an alternative for those non-compliant to use of a continuous positive airway pressure (CPAP) mask for a night's sleep, the current standard therapy for OAS, either because they can't or won't tolerate it.

The Inspire II is a closed-loop system consisting of three parts: a cuff that is implanted, under the chin, around the hypoglossal nerve; a pulse generator implanted beneath the collar bone sending low pulses of electricity, so low that sleep is not disturbed; and below that, under the pectoral muscle, a sensor. The sensor monitors the person's respiration so that the electric pulses are delivered to the muscles around the throat and airway to improve the tension and relaxation of the airway, much the way cardiac pacing regularizes the heartbeat.

Herbert said, "We're basically doing the same thing [as a pacemaker] but we're stimulating the hypoglossal nerve that enervate the tongue and providing that on back to the upper airway."

Patients have a programming device used to turn the device on at bedtime and to turn the unit off during non-sleep periods. A controller unit is used by the physician to monitor the therapy and make adjustments to fit patient physiology.

The first implant in the Inspire II clinical study was done at University Hospital (Antwerp, Belgium), the company said, in collaboration with Paul Van de Heyning, MD, professor of otorhinolaryngology and head and neck surgery and Wilfried De Backer, MD, professor of respiratory medicine.

Inspire also reported receiving FDA approval to begin implants in the U.S., expected sometime next month.

Van de Heyning implanted four of the eight patients in the initial trial. He said this experience "demonstrated the value of electrical stimulation of the hypoglossal nerve to prevent closure of the upper airway during sleep. Based on these results and the improvements to the Inspire II system, we believe that the implantable device could be the answer to helping patients with OSA."

The electric pulses were first tested in animals to demonstrate the neural/muscle response and to demonstrate safety. Early work in humans was done by stimulating the tongue. "If we can stimulate a certain muscle group of the tongue, that showed the mechanism of action," Herbert said.

He noted that CPAP technology is effective therapy, but that about 50% of those that might benefit from CPAP use can't tolerate wearing a mask during sleep or aren't compliant with its use. This group therefore is the target population for the Inspire II system.

Inspire cites estimates that one in 15 adults has moderate-to-severe OSA and that 250,000 patients are newly diagnosed in the U.S. each year.

Because the device is implantable, around the delicate nerves of the neck, the device will be placed on a PMA regulatory path, a hurdle Herbert doesn't find particularly difficult, given his experience and that of his management team out of Medtronic. He said that with approval, the device could reach U.S. commercialization by 2011 or 2012.

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