Neurostimulation is now firmly established as a therapy for disorders including the motor symptoms of Parkinson’s disease, epilepsy and depression. Next month, an FDA advisory panel will decide whether a similar technique has a future in the US as a treatment for obstructive sleep apnoea (OSA).
The Inspire II Upper Airway Stimulator, developed by Inspire Medical Systems, will be assessed by the FDA’s Anesthesiology & Respiratory Therapy Devices panel on February 20. It is based on technology spun out from Medtronic in 2007 and works by delivering shocks to the hypoglossal nerve, moving the patient’s tongue forwards and preventing it obstructing their breathing. With compliance with current OSA devices poor, a positive vote could allow Inspire to breathe new life into the US market.
At the moment, treatment for OSA focuses on continuous positive airway pressure (CPAP) devices, which keep patients’ airways open by using mild air pressure, essentially forcing air down patients’ throats. The patient has to wear a mask covering the nose or mouth or both, and sleep can be disrupted by the sensation of air flow or the noise of the pump.
With this in mind it is easy to see why patients are resistant to using these devices – long-term compliance with CPAP is estimated at around 50-80%, fairly low considering that OSA patients can die in their sleep.
Inspire II is implanted in a similar fashion to Cyberonics’ VNS device, which stimulates the vagus nerve in the neck in order to treat epilepsy (Therapeutic focus – Responsive neurostimulator technology shocks epilepsy market, December 10, 2013). A stimulator (pictured) is placed permanently in the chest, with leads attached to the hypoglossal nerve in the jaw. This requires a second incision just under the chin.
Naturally an implant will eliminate adherence issues, something the FDA will doubtless take into account when considering whether to approve Inspire II. But it will not concern the panel, which will instead focus on data from the US pivotal trial, Star, which enrolled 126 patients with moderate to severe OSA who were intolerant to CPAP.
Use of Inspire II caused a statistically significant 68% median reduction in apnoea hypopnea index (AHI) – a measure of incidences of pauses in breathing of at least 10 seconds and of incidences of shallow breathing. Patients with Inspire II implants had an average of 9.0 events per hour compared with 29.3 events per hour in untreated patients. The device also produced a 70% median reduction in oxygen desaturation index.
In a second phase of the study, 46 patients responding to treatment after a year’s use were randomised to either continue therapy or have the device switched off for a week. A significant difference was seen between the two groups with respect to the change in AHI scores; those whose therapy had been withdrawn had a score of 25.8 compared with 7.6 events per hour in the continuous stimulation group.
The efficacy data look good, then. As for safety, the rate of procedure-related serious adverse events was less than 2%: two patients needed to have the device repositioned to resolve discomfort. Temporary tongue weakness was seen in 18% of patients; this resolved over a period of days to weeks.
The lack of a control group ought to be acceptable given that Inspire is seeking approval in patients who are unsuitable for other therapy.
But almost a third of the patients in the trial saw no benefit from the stimulator, and there are suggestions that it might be unsuitable for obese patients, in whom OSA is more common. The Star trial excluded patients with a body mass index of 32 or more; obesity is defined as a BMI of more than 30.
Perhaps the most probable outcome from the panel meeting will be a recommendation for approval in a fairly narrow population: OSA patients with a body mass index of less than 32 – or maybe less than 30 – who cannot or will not accept CPAP therapy.
Still, a limited approval is still something, and OSA is a growing problem in the US. The panel vote could open a whole new market for neurostimulation.
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