← Product Code [MNQ](/productcode/MNQ) · P130008S090 # Inspire Upper Airway Stimulation System (P130008S090) _Inspire Medical Systems · MNQ · Jun 8, 2023 · Anesthesiology · APPR_ **Canonical URL:** https://fda-staging.innolitics.com/device/P130008S090 ## Device Facts - **Applicant:** Inspire Medical Systems - **Product Code:** [MNQ](/productcode/MNQ.md) - **Decision Date:** Jun 8, 2023 - **Decision:** APPR - **Device Class:** Class 3 - **Review Panel:** Anesthesiology - **Attributes:** Therapeutic, Real-World Evidence, Pediatric ## Real-World Evidence | Submission | Device | Sponsor | RWD Sources | RWE Use Summary | Key Tags | | --- | --- | --- | --- | --- | --- | | P130008S090 · Jun 8, 2023 | Inspire Upper Airway Stimulation System | Inspire Medical Systems | ADHERE Registry (multi-center, prospective, observational registry) | The ADHERE registry provided real-world clinical outcomes (AHI, ESS, therapy usage, and adverse events) for patients with AHI >65 and BMI >32 to support the expansion of the device's indications and safety labeling. | ADHERE Registry; Observational Study; Real-world clinical outcomes; Standard of care | ### Clinical Evidence | Study Design | Population | Comparator | Key Endpoints | | --- | --- | --- | --- | | ADHERE Registry; Multi-center, prospective, observational registry; Follow-up/Duration: Annual visits up to 2 years post-implant; Study Period: Data as of July 22, 2022 | Patients implanted with Inspire UAS undergoing standard of care management; Sample Size: 3,988 total enrolled; 57 patients (AHI 65-100) and 279 patients (BMI 32-40) included in specific analyses | Not applicable for this study | AHI, ESS, Therapy Usage, CGI, Patient Satisfaction, and Adverse Events | ## Indications for Use Inspire Upper Airway Stimulation (UAS) is used to treat a subset of patients with moderate to severe obstructive sleep apnea (OSA) (apnea-hypopnea index [AHI] of greater than or equal to 15 and less than or equal to 100). Inspire UAS is used in adult patients 22 years of age and older who have been confirmed to fail or cannot tolerate positive airway pressure (PAP) treatments (such as continuous positive airway pressure [CPAP] or bi-level positive airway pressure [BPAP] machines) and who do not have a complete concentric collapse at the soft palate level. PAP failure is defined as an inability to eliminate OSA (AHI of greater than 15 despite PAP usage), and PAP intolerance is defined as: (1) Inability to use PAP (greater than 5 nights per week of usage; usage defined as greater than 4 hours of use per night), or (2) Unwillingness to use PAP (for example, a patient returns the PAP system after attempting to use it). Inspire UAS is also indicated for use in patients between the ages of 18 to 21 with moderate to severe OSA (15≤AHI≤100), and pediatric patients ages 13 to 18 years with Down syndrome and AHI greater than 10 and less than 50 who: - Do not have complete concentric collapse at the soft palate level - Are contraindicated for or not effectively treated by adenotonsillectomy - Have been confirmed to fail, or cannot tolerate PAP therapy despite attempts to improve compliance - Have followed standard of care in considering all other alternative/adjunct therapies ## Device Story Implantable system treats moderate-to-severe OSA; consists of IPG, stimulation lead, and sensing lead. IPG implanted subcutaneously in upper chest; sensing lead placed in intercostal space; stimulation lead cuff placed around hypoglossal nerve. System detects respiratory effort via piezoelectric pressure sensor; algorithm synchronizes electrical stimulation of hypoglossal nerve to late expiratory/inspiratory phases; causes tongue protrusion to maintain airway patency. Physician configures settings via tablet-based programmer; patient uses handheld remote to activate/deactivate therapy and adjust amplitude within prescribed limits. Used in clinical/home settings. Benefits include reduced OSA severity, improved sleep quality, and increased therapy compliance compared to PAP. Risks include surgical complications, nerve trauma, stimulation discomfort, and potential for lead/IPG revision. ## Clinical Evidence Evidence based on ADHERE Registry (prospective, observational, multi-center). Analysis included 57 patients with 65 This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). 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GENERAL INFORMATION Device Generic Name: Implantable Upper Airway Stimulation for Obstructive Sleep Apnea (OSA) Device Trade Name: Inspire Upper Airway Stimulation System Device Procode: MNQ Applicant's Name and Address: Inspire Medical Systems, Inc. 5500 Wayzata Blvd., Suite 1600 Golden Valley, MN 55416 Date(s) of Panel Recommendation: None Premarket Approval Application (PMA) Number: P130008/S090 Date of FDA Notice of Approval: June 8, 2023 The original PMA (P130008) was approved on April 30, 2014 and is indicated to treat a subset of patients with moderate to severe obstructive sleep apnea (OSA) who have been confirmed to fail or cannot tolerate positive airway pressure (PAP) treatment and who do not have a complete concentric collapse at the soft palate level. The original PMA was approved in adult patients 22 years of age or older. Supplement P130008/S039 expanded the indications for the Inspire UAS system to include adolescent patients between 18 and 21 years of age and supplement P130008/S089 expanded the indications to include pediatric patients with Down syndrome between 13 and 18 years of age. Supplement P130008/S090 expands the indications further to include OSA patients, 18 years of age or older, with AHI ≤100. The supplement also updates the BMI warning to note that the BMI upper limit For which safety and effectiveness data is available has increased from BMI≤32 to BMI≤40. ## II. INDICATIONS FOR USE Inspire Upper Airway Stimulation (UAS) is used to treat a subset of patients with moderate to severe obstructive sleep apnea (OSA) (apnea-hypopnea index [AHI] of greater than or equal to 15 and less than or equal to 100). Inspire UAS is used in adult patients 22 years of age and older who have been confirmed to fail or cannot tolerate positive airway pressure (PAP) treatments (such as continuous positive airway pressure [CPAP] or bi-level positive airway ---PMA P130008-S090: FDA Summary of Safety and Effectiveness Data 1 of 26 {1} pressure [BPAP] machines) and who do not have a complete concentric collapse at the soft palate level. PAP failure is defined as an inability to eliminate OSA (AHI of greater than 15 despite PAP usage), and PAP intolerance is defined as: (1) Inability to use PAP (greater than 5 nights per week of usage; usage defined as greater than 4 hours of use per night), or (2) Unwillingness to use PAP (for example, a patient returns the PAP system after attempting to use it). Inspire UAS is also indicated for use in patients between the ages of 18 to 21 with moderate to severe OSA (15≤AHI≤100), and pediatric patients ages 13 to 18 years with Down syndrome and AHI greater than 10 and less than 50 who: - Do not have complete concentric collapse at the soft palate level - Are contraindicated for or not effectively treated by adenotonsillectomy - Have been confirmed to fail, or cannot tolerate PAP therapy despite attempts to improve compliance - Have followed standard of care in considering all other alternative/adjunct therapies ### III. CONTRAINDICATIONS - Central + mixed apneas > 25% of the total apnea–hypopnea index (AHI) - Any anatomical finding that would compromise the performance of upper airway stimulation, such as the presence of complete concentric collapse of the soft palate - Any condition or procedure that has compromised neurological control of the upper airway - Patients who are unable or do not have the necessary assistance to operate the sleep remote - Patients who are pregnant or plan to become pregnant. UAS therapy has not been evaluated for safety or efficacy during pregnancy. - Patients with an implantable device that may be susceptible to unintended interaction with the Inspire system. Consult the device manufacturer to assess the possibility of interaction. - Patients who require magnetic resonance imaging (MRI) other than what is specified in the MR Conditional labeling PMA P130008-S090: FDA Summary of Safety and Effectiveness Data 2 of 26 {2} #### **IV. WARNINGS AND PRECAUTIONS** The warnings and precautions can be found in the Inspire Upper Airway Stimulation System labeling. #### **V. DEVICE DESCRIPTION** The Inspire UAS system consists of implanted components including the implantable pulse generator (IPG), stimulation lead and sensing lead, and external components such as the physician programmer and the patient remote. See Figure 1 below depicting the implantable components and their relative positioning. The IPG detects the patient's respiratory effort and maintains airway patency with mild stimulation of the hypoglossal nerve during inspiration. The physician is able to configure the stimulation settings using the external physician programmer. The patient sleep remote allows the patient to turn therapy on before they go to sleep and to turn therapy off when they wake up. It also provides the ability to pause therapy and adjust stimulation amplitude within physician-defined limits that are within the therapeutic range of treatment. ![img-0.jpeg](img-0.jpeg) **Figure 1:** Inspire® system components and implant location Table 1 provides a description of the implanted and external components of the Inspire® UAS system. PMA P130008-S090: FDA Summary of Safety and Effectiveness Data 3 of 26 {3} Table 1: Inspire® UAS System Components | Component | Description | | --- | --- | | **Implanted Components:** | | | Model 3028 Implantable Pulse Generator (IPG) | The IPG contains electronics and a battery sealed inside a titanium case. The surgeon implants the IPG subcutaneously, below the clavicle in the upper chest, and connects to the stimulation lead and sensing lead. The algorithm synchronizes stimulation of the hypoglossal nerve to deliver stimulation during the late expiratory and through the inspiratory phase of respiration. Model 3028 is a second generation IPG replacing the Model 3024 and is smaller and MR conditional. | | Model 4063 Stimulation Lead | The stimulation lead includes a cuff electrode with a guarded bipolar configuration. The surgeon positions the cuff around a patient's hypoglossal nerve and connects the connector tip end of the lead to the IPG. The cuff electrodes apply electrical current that stimulates the hypoglossal nerve, which causes the base of the tongue to protrude forward in order to open the upper airway. | | Model 4323 and Model 4340 Sensing Leads | The sensing lead is placed in the intercostal space and contains a piezoelectric differential pressure sensor for detecting respiratory signals. | | **External Components:** | | | Model 2500 and Model 2580 Sleep Remote | The patient sleep remote is a handheld device. It is placed on the skin over the implant and provides a non-invasive means for patient to activate the IPG, to adjust the stimulation parameters (within the physician prescribed limits), and to check battery status. | | Model 2740 Physician Programmer | The physician programmer consists of a tablet computer and a telemetry cable. The telemetry head communicates with the IPG through the skin via short-range radio-frequency (RF) telemetry. Telemetry communication allows the physician to noninvasively interrogate and configure the IPG settings. The physician programmer has the capability to monitor respiratory waveforms, configure stimulation modes, adjust stimulation parameter values, and store waveforms and settings. | # VI. ALTERNATIVE PRACTICES AND PROCEDURES PMA P130008-S090: FDA Summary of Safety and Effectiveness Data 4 of 26 {4} There are several other alternatives for the correction of obstructive sleep apnea in patients with AHI>65 and/or BMI ≤40 who have failed or are intolerant of PAP. These include upper airway surgical procedures and mandibular advancement devices (MAD). Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle. ## **VII. MARKETING HISTORY** The Inspire UAS device has been commercially available in the U.S. since April 30, 2014. The device received CE Mark approval on October 20, 2010, and has been commercially available in the European Union since that time. The device has been commercially available in Japan since June of 2018, and in Australia since June 8, 2020. The Inspire UAS device has not been withdrawn from the market in any country. ## **VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH** Below is a list of the potential adverse effects (e.g., complications) associated with the use of the device. - Damage to blood vessels in the vicinity of implant - Excessive bleeding - Nerve trauma or damage - Allergic and/or rejection response to the implanted materials - Infection - Local irritation, seroma, hematoma, erosion, or swelling - Persistent pain, numbness, or inflammation at the implant site - Discomfort from the stimulation - Tongue movement restrictions, irritation resulting from tongue abrasions on preexisting sharp or broken teeth - Tongue soreness or weakness - Problems with swallowing or speaking - Undesirable change in stimulation over time, possibly related to tissue changes around the electrode(s), shifts in electrode position, loose electrical connections, or lead fractures - Fibrosis to the extent that it makes it difficult to remove the system without damaging surrounding structures - Dry mouth - Other acute symptoms (i.e., headaches, coughing, choking, dysphasia, and speech related events) PMA P130008-S090: FDA Summary of Safety and Effectiveness Data 5 of 26 {5} - Scarring (due to picking at the device/ implant site) and keloid formation from implantation - Cellulitis at surgical site - Insomnia - Pneumothorax - Rhabdomyolysis For the specific adverse events (AE) that occurred in the clinical studies, please see Section X below. # IX. SUMMARY OF NONCLINICAL STUDIES All preclinical data to demonstrate safety and effectiveness of the Inspire UAS system has been reviewed by FDA under the original PMA (P130008) and subsequent supplements. No new preclinical information was required for the expansion of the indications for use (IFU). # X. SUMMARY OF PRIMARY CLINICAL STUDIES Real world evidence data from Inspire Medical's ADHERE Registry (ongoing observational study) was used to support the expanded indication for use and update to the BMI warning. The ADHERE Registry is a multi-center, prospective, observational registry, conducted in the United States and Europe. The ADHERE registry is designed to capture data on 5,000 patients implanted with Inspire UAS, undergoing standard of care management following UAS implant. All patients who undergo implant of the Inspire UAS system are eligible to participate in the registry if they are willing to provide consent and have a life expectancy of at least one year. IRB approval is required for each clinical center to be included in the Registry. In addition, subjects must consent to have their data collected and reported (unless a waiver of consent was provided by the IRB). Out of 3,988 subjects enrolled in the registry as of July 22, 2022, 57 patients were included in the analysis to support expanding the indication of the UAS to patients with 6565 and BMI>32, Inspire evaluated efficacy using data from the ADHERE registry data using at least one of the following values recorded at final visit: AHI, ESS, Therapy Usage, CGI (Clinical Global Impression), and/or Patient Satisfaction data.: Safety was evaluated via an analysis of all reported adverse events. # A. AHI ADHERE DATA ANALYSIS: Table 2 below provides demographic characteristics of patients included in the analysis to support expanding the indication of the Inspire UAS to patients with AHI≤100. For the analysis data from patients with baseline AHI>65 was compared with data from patients PMA P130008-S090: FDA Summary of Safety and Effectiveness Data 6 of 26 {6} with baseline AHI of $15 < \text{AHI} \leq 65$ and data in each table below, therefore, includes these two groups. **Table 2: Demographics of High AHI Patients.** | Variable | AHI≤65 | 6565 (66.7%). Thus, both groups received similarly effective treatment for their OSA. Given this finding, it follows that there was a significant difference when comparing reduction in AHI for these groups, with patients that had an AHI>65 at baseline showing greater reduction in AHI. Further analysis of the ADHERE data similarly showed change from baseline to final ESS for both AHI groups, on average. There also was not a statistical difference in Final ESS or Change in ESS when both AHI groups were compared with each other. Thus, sleepiness symptoms were similar in both groups. The safety profile reported in the population with baseline 6532) in regard to Final AHI and Change in AHI, nor response rate from Baseline to Final Visit. The response rate of both low and high BMI groups is higher than response rates (~50%) for other typical surgical options for OSA. When the data on the BMI groups was further analyzed using groups of BMI≤32, 3265 and BMI ≤ 40 is limited to upper airway surgeries and Mandibular Advancement Devices (MAD) intended to enlarge the airway. Upper airway surgeries often have response rates less than 50%, and even lower response in patients with higher AHI and BMIii,iii. Airway surgeries also have higher post-operative PMA P130008-S090: FDA Summary of Safety and Effectiveness Data 21 of 26 {21} complication rates than Inspire UAS, which may limit adoption of upper airway surgery in more severe OSA and obese patientsiv. Oral Appliances also have challenges in this populationv. Since 2012, it has been widely accepted that oral appliances are primarily indicated for mild-to-moderate OSA. Further, the Agency for Healthcare Research and Quality has also concluded that the clinical evidence for upper airway surgeries efficacy is insufficient.vi Therefore, the clinical needs of the CPAP-intolerant OSA patient population with AHI>65 and/or BMI>32 were not adequately met by currently available treatment options. Inspire therapy provides an alternative treatment option for OSA patients who are not effectively treated by current treatment options. Given the seriousness of the co-morbidities associated with untreated OSA, and the low rate of CPAP compliance, the magnitude of Inspire therapy's benefits is substantial for OSA patient population with 65