“There’s been a number of developments just in the past year that are altering the field,” Dr. Thomas M. Kaffenberger, MD, said at the start of the Eye & Ear Foundation’s September 24 webinar, “Waking Up to Change: The New Era of Sleep Apnea Treatments.” Dr. Kaffenberger is Assistant Professor of Otolaryngology-Head & Neck Surgery at the University of Pittsburgh and boarded in otolaryngology as well as sleep medicine.
Disease Burden
Obstructive sleep apnea (OSA) impacts approximately 1 billion adults across the world. The U.S. alone has about 54 million people with OSA. This does not even include the number of patients who do not have OSA but who snore. OSA is one of the most common pathologies that otolaryngologists treat. The condition affects quality of life and increases risk of cardiovascular disease and motor vehicle accidents.
Historically there were two main options for OSA treatment: CPAP and sleep surgery via the uvulopalatopharyngoplasty (UPPP). There have been advances since then, and to a certain extent, these silos have “started to merge in a much more fluid, dynamic way across the entire sleep medicine field,” Dr. Kaffenberger said.
OSA Toolbox
The current toolbox for treating OSA includes oral appliances, CPAP, weight loss, nasal surgery, nerve stimulation, pharyngeal surgery, and skeletal surgery.
Pittsburgh is at the forefront of sleep care, including leading advances and building the present toolbox. Dr. Rob Rogers, DMD, is a recently retired Pittsburgh based sleep dentist and one of the founders of the American Academy of Dental Sleep Medicine. He helped build the sleep dentistry field from the ground up in the 1990s.
Respironics – now Phillips Respironics – is also based in Pittsburgh. And UPMC has been intimately involved in implementing hypoglossal nerve stimulation therapies, led by Division Chief Dr. Ryan Soose, MD, and former chair Dr. Jonas Johnson, MD, FACS. Pittsburgh is home to the Center for Sleep and Circadian Science, led by Dr. Dan Buysse MD, “one of the foremost opinion leaders when it comes to sleep and insomnia.” In addition, Pittsburgh has Drs. Sanjay Patel, MD, MS, and Patrick Strollo, MD, FACP, FCCP, FAASM, two of the foremost OSA researchers in the world.
Implantable Neurostimulation System
Hypoglossal nerve stimulation (HGNS) was originally approved in 2014 with the Inspire Medical Systems device. Dr. Kaffenberger likens it to a pacemaker for the tongue. It senses your breathing pattern and pushes the tongue forward. Patients can control it with a remote control, modifying or adjusting the therapy as needed.
HGNS has been a game-changer when it comes to OSA care. Of note, Dr. Soose was the first to implant the device in the United States.
Inspire has now progressed to a new generation, the Inspire V. Drs. Soose and Kaffenberger were the first surgeons to implant the Inspire V in the United States. This newer model now uses two hardware components instead of three. It has more advanced programming, and the surgery is about 20 minutes shorter. At UPMC, the vast majority of cases are now Inspire V; the VA should be transitioning over to it in the next couple of months.
The FDA approved a bilateral HGNS two months ago – the Genio device from Nyxoah. This device uses paddle electrodes that go onto the distal portions of the hypoglossal nerve, requiring just one incision under the skin. There is no respiratory sensing lead, an external battery pack, and it is MRI compatible.
GLP-1
In the past couple of years, due to the introduction of GLP-1s, there have been seismic changes when it comes to weight loss and diabetes medicine. They cause insulin release, act as a brake for the GI system, and result in a feeling of satiety. The RX provides lasting stimulation by decreasing calories and increasing cardiovascular and neural benefits.
From an OSA standpoint, a GLP-1 medication called tirzepatide was used in the SURMOUNT-OSA clinical trial, published in the New England Journal of Medicine. Patients were randomized to receive a weekly injection in addition to diet and exercise. These patients saw a 50% reduction over a year in OSA severity, with 20% weight loss/year. “This is a pretty profound impact, no question about it,” Dr. Kaffenberger said.
However, if you dig into the data and look through the rate of clinically significant reduction (meaning no further treatment may be needed) in OSA, 42-50% patients did not need further treatment. The number drops closer to 26-35% when you account for the treatment effect in the placebo group. Ultimately, there will still be patients who will need some form of treatment after GLP-1 therapy.
This is also a drug that you have to keep taking to maintain weight loss. In a different clinical trial, this one called SURMOUNT-4, patients on tirzepatide were randomized to stop therapy. These patients saw weight return. Ultimately, they had a 10% weight loss compared to 25% in patients who stayed on tirzepatide. This speaks to the importance of adherence, which can be challenged by insurance coverages and medication shortages, Dr. Kaffenberger said.
How to Implement the Current Toolbox?
With the new therapies now out there, how do we expand the toolbox and in what order? What are the opportunities for combination therapy in HGNS? One of Dr. Soose’s brainchilds was to take other types of staging technology – like the ones used in oncology TNM staging – and implement it from an OSA standpoint. This provides more definition and insight into treatment profiles and allows providers to think about what patient type would respond well to which treatment. This new staging will allow them to establish that framework and test combination therapies.
The Future OSA Toolbox
There is a lot in the pipeline. In addition to Inspire and Nyxoah, about six other companies are either starting or ramping up clinical trials. The one closest to FDA approval is LivaNova for the Aura6000. This device is placed on the proximal hypoglossal and has a battery that requires charging. There is no respiratory sensor. A cyclical activation of electrodes prevents muscle fatigue and relies on organization of nerve fascicles to selectively stimulate.
Their Osprey trial had a press release that claimed a comparable reduction in sleep apnea severity as compared to the Inspire STAR trial and Nyxoah DREAM trial.
Dr. Dave Kent, MD, at Vanderbilt is doing pioneering work, taking stimulation in a new direction. He did his otolaryngology residency with Dr. Soose at Pitt. He is looking into lengthening the airway to pull down on the upper airway, stimulating a nerve called the Ansa cervicalis. Several companies are trying to take this to market. Dr. Kaffenberger said, “It’s going to be very exciting.”
Targeted fat loss treatments like coolsculpting are also possibilities. There is good evidence that if fat cells are exposed to cold, they shrink. This has been part of the aesthetics world for a number of years, but a company is now taking this and applying it to the upper airway. The upper airway holds a lot of fat, particularly the tongue. MRI studies can detect and determine the amount of fat.
Cryosa is a company bringing this therapy to market and UPMC is one of six sites for its initial U.S. clinical trial. This is a single treatment done in the operating room in which a probe is placed on the very back of the tongue while the patient is asleep to deliver a cold therapy treatment to the upper airway. The hope is to begin enrollment by the end of the year.
Drug companies are also looking at modifying GLP-1 treatments from injectables to oral medicines. A couple of months ago, the New England Journal of Medicine published a study on early Type 2 diabetes that had impressive results. “I would anticipate that the OSA world will be having these in the not-too-distant future as well,” Dr. Kaffenberger said.
Other pills for sleep apnea are coming. Combining atomoxetine (a stimulant used for ADHD) plus oxybutynin (used for overactive bladder) might be an option. The MARIPOSA Phase 2 clinical trial showed approximately 50% reduction in patients after four weeks of nightly therapy when compared to the placebo. The company, Apnimed, has now completed two Phase 3 Trials, which were led by Drs. Patel and Strollo. According to the company’s press release, SynAIRgy and LunAIRo Phase 3 trials found a 45-51% reduction in OSA severity. This still has to be approved by the FDA but could be a very valuable addition to the toolbox.
As the toolbox continues to expand, there are a ton of things coming out, as well as a lot of work being done trying to implement these treatments in a thoughtful and personalized manner. It is important to note that the “old” therapy – i.e. CPAP and UPPP – have not been static either. Dr. Kaffenberger did not have time to touch on some newer aspects with CPAP and pharyngeal surgery but suffice to say these are also seeing improvements as well.
Take Home Points
Dr. Kaffenberger pointed out that the sleep medicine field is one of the youngest when it comes to medical care, so in many ways it is still early days in terms of experimentation and learning how to best treat patients.
The UPMC Otolaryngology-Head & Neck Surgery Sleep Division is uniquely positioned to figure out how to apply these therapies. In fact, it is the only institution in the world that has three physicians who are dual boarded in sleep medicine and otolaryngology: Dr. Soose, Dr. Rachel Whelan, MD, and Dr. Kaffenberger. In addition, the team has three excellent sleep-focused PAs. “We are uniquely positioned to be leaders at the forefront of this new world of OSA care,” Dr. Kaffenberger said. “It is an extremely exciting time for us.”