ZOLL Announces Five-Year Study Confirming Safety, Efficacy and Beneficial Effects of Long-Term Transvenous Phrenic Nerve Stimulation (the Remedē System)

CONTACT:

Matt Hogan

ZOLL Medical Corporation

ZOLL ANNOUNCES FIVE-YEAR STUDY CONFIRMING SAFETY, EFFICACY AND BENEFICIAL EFFECTS OF LONG-TERM TRANSVENOUS PHRENIC NERVE STIMULATION (THE REMEDĒ SYSTEM)

Study results published in the peer-reviewed Nature and Science of Sleep show sustained improvement in sleep disordered breathing, arousals, sleep architecture, and daytime sleepiness through five years

May 17, 2021 — CHELMSFORD, MASS. — ZOLL^® Medical Corporation, an Asahi Kasei company that manufactures medical devices and related software solutions, announced today that the peer-reviewed journal Nature and Science of Sleep has published five-year results from the remedē System Post Approval Study. The data show sustained safety and efficacy of transvenous phrenic nerve stimulation for the treatment of moderate to severe central sleep apnea (CSA). The remedē^® System, the only implantable device approved by the U.S. Food and Drug Administration (FDA) to treat moderate to severe CSA in adult patients with reduced cardiac function,¹ was developed by Respicardia^®, Inc., which was acquired by ZOLL in April 2021.

The Post Approval Study was led by Dr. Maria Rosa Costanzo, Principal Investigator for the Pivotal Trial of the remedē System and Medical Director at Edward Hospital Center for Advanced Heart Failure and Heart Failure Research at Advocate Heart Institute, with contributions from Dr. Shahrokh Javaheri, Dr. Piotr Ponikowski, Dr. Olaf Oldenburg, Dr. Ralph Augostini, Dr. Lee Goldberg, Dr. Christoph Stellbrink, Dr. Henrik Fox, Dr. Alan Schwartz, Dr. Sanjaya Gupta, Scott McKane, Timothy Meyer, and Dr. William Abraham.

The five-year data show sustained improvements from baseline that were highly consistent with the previously published six-, 12-, 24-, and 36-month results.² The five-year results include:^3,4

96% reduction in central apneas
Overall apnea hypopnea index (AHI) reduced by 22 events/hour of sleep
Arousals reduced by 14 events/hour of sleep
14 percentage point (absolute) increase in deep sleep (N2–REM) and a 19 percentage point decrease in light stage sleep (N1)
Sustained improvement in daytime sleepiness
Consistent safety, in line with previously published data

“It is an important milestone for a therapy to demonstrate sustained patient safety and benefit over five years,” said Dr. Robin Germany, Chief Medical Officer of ZOLL Respicardia. “Phrenic nerve stimulation continues to show a significant and durable improvement in patient outcomes, including reduction in sleep apnea events, improvement in sleep architecture, and improvements in quality of life metrics. We congratulate all of the coauthors, study investigators, and patients who have contributed to the data collection and publication of this five-year study. We will continue to advance research on central sleep apnea and transvenous phrenic nerve stimulation as we increase access to the therapy for patients in need.”

“Patients with central sleep apnea have historically been underserved, both in terms of research into the disease and the development of effective therapies designed to treat it,” said Peter Sommerness, President of ZOLL Respicardia. “Transvenous phrenic nerve stimulation continues to deliver remarkable results, giving clinicians and patients confidence in the long-term safety and efficacy of the therapy.”

The remedē System was approved to treat moderate to severe CSA in adult patients by the FDA in 2017.¹ The remedē System is an implantable device that activates automatically each night to stimulate a nerve in the chest (phrenic nerve) that sends signals to the breathing muscles (diaphragm) to help restore a normal breathing pattern.⁵ The Post Approval Study followed patients from the pivotal trial through five years post implant.

Central sleep apnea (CSA) is a serious breathing disorder that disrupts the normal breathing pattern during sleep and negatively affects sleep quality, quality of life, and is associated with poor outcomes. CSA results from the brain's inability to send appropriate signals to the respiratory muscles to stimulate breathing. Many patients with CSA also have heart disease, especially heart failure.⁶ Within this population, patients with CSA are at increased risk for hospitalizations and even death.^7,8

About ZOLL Medical Corporation

ZOLL Medical Corporation, an Asahi Kasei company, develops and markets medical devices and software solutions that help advance emergency care and save lives, while increasing clinical and operational efficiencies. With products for defibrillation and cardiac monitoring, circulation enhancement and CPR feedback, supersaturated oxygen therapy, data management, ventilation, and therapeutic temperature management, ZOLL provides a comprehensive set of technologies that help clinicians, EMS and fire professionals, as well as lay rescuers, improve patient outcomes in critical cardiopulmonary conditions. For more information, visit www.zoll.com.

About Asahi Kasei

The Asahi Kasei Group contributes to life and living for people around the world. Since its foundation in 1922 with ammonia and cellulose fiber business, Asahi Kasei has consistently grown through the proactive transformation of its business portfolio to meet the evolving needs of every age. With more than 40,000 employees around the world, the company contributes to sustainable society by providing solutions to the world’s challenges through its three business sectors of Material, Homes, and Health Care. Its health care operations include devices and systems for acute critical care, dialysis, therapeutic apheresis, transfusion, and manufacture of biotherapeutics, as well as pharmaceuticals and diagnostic reagents. For more information, visit www.asahi-kasei.com.

IMPORTANT SAFETY INFORMATION

Indications for Use
The remedē^® System is an implantable phrenic nerve stimulator indicated for the treatment of moderate to severe central sleep apnea (CSA) in adult patients.

Contraindications
The remedē System is contraindicated for the following:

Patients with an active infection
Patients known to require magnetic resonance imaging (MRI)

Warnings

Diathermy — Do not use shortwave diathermy, microwave diathermy, or therapeutic ultrasound diathermy (collectively referred to as diathermy) on patients implanted with the remedē System.
Electric Shock — When operating under AC power, the remedē System Programmer must be connected to a grounded power source to avoid risk of electric shock.
Concomitant Active Implantable Devices — Use the remedē System with caution in patients with an active implantable device that may be susceptible to unintended interaction with the remedē System. Consult Respicardia to assess the possibility of interaction.
Patients with Evidence of Phrenic Nerve Palsy — Therapy with the remedē System may be ineffective in patients who have evidence of phrenic nerve palsy.
Pediatric Use — The safety and effectiveness of the remedē System has not been established for pediatric use.

Precautions
It is recommended that testing for oversensing of remedē stimulation therapy by the concomitant cardiac device occur at the time of implant and prior to initiating remedē System therapy in patients with a concomitantly implanted cardiac device. Use remedē System therapy with caution in pacemaker-dependent patients without a physiologic escape rhythm. Device interaction may lead to over or undersensing resulting in a loss of pacing. The safety and effectiveness of the remedē System during pregnancy has not been established. See the Device Manual for detailed information regarding the implant procedure, indications, contraindications, warnings, precautions, and potential complications/adverse events.

Adverse Effects
Possible adverse events which may be associated with the use implantation and use of the remedē System include, but are not limited to, the following: adverse contrast dye reaction such as allergic reaction, pulmonary edema, or worsening renal function, adverse reaction to radiation exposure, thromboembolism, air embolism, bleeding, cardiac perforation including tamponade, hematoma, seroma, local bruising or swelling, hypotension, local wound healing issues at device implant site including wound dehiscence, pocket erosion, extrusion, movement of implanted device, keloid formation, pneumothorax, hemothorax, vascular damage, e.g., venous dissection, perforation, adverse biocompatibility reaction to the implanted system, infection, lead breakage, lead dislodgement, lead not connected or secured appropriately in device header, implantable device malfunction, requirement for more energy to stimulate the nerve or ineffective stimulation, venous occlusion, crosstalk with another implanted device, disrupted sleep, muscle fatigue or discomfort in diaphragm, chest or abdomen from appropriate stimulation, nerve dysfunction, perturbation of blood gases causing hypoxia, hypercapnea and/or hypocapnea, inappropriate sensations, worsening heart failure, respiratory status or overall health, anxiety, arrhythmia, including ventricular fibrillation, death, depression, hypotension, pain, skin irritation or local allergic reaction, thrombus or embolism, potentially leading to pulmonary embolism or stroke.

CAUTION: Federal law (USA) restricts this device to sale by or on the order of a physician. Rx only. Prior to use, please see the complete “Directions for Use” for more information on Indications, Contraindications, Warnings, Precautions, Adverse Events, and Operator’s Instructions.

¹ FDA PMA P160039. https://www.fda.gov/medical-devices/recently-approved-devices/remeder-system-p160039
² Fox H., et al. Sleep. 2019;42:11. https://doi.org/10.1093/sleep/zsz158
³ Costanzo MR, Javaheri S, Ponikowski P, Oldenburg O, Augostini R, Goldberg LR, Stellbrink C, Fox H, Schwartz AR, Gupta S, McKane S, Meyer TE, Abraham WT. Transvenous Phrenic Nerve Stimulation for Treatment of Central Sleep Apnea: Five-Year Safety and Efficacy Outcomes. Nat Sci Sleep. 2021;13:515-526 https://doi.org/10.2147/NSS.S300713
⁴ Javaheri S., et al. Chest. 2020;158:4(suppl): A2412-A2413.
⁵ Costanzo M.R., et al. The Lancet. 2016;388:974–82.
⁶ Bekfani T, Abraham WT. Europace. 2016;18(8):1123–34. Epub 2016 May 26.
⁷ Khayat R, et al. J Card Fail. 2012;18:534–40.
⁸ Khayat, R et al. European Heart J. 2015;36 1463–69.

Copyright © 2021 ZOLL Medical Corporation. All rights reserved. ZOLL is a registered trademark of ZOLL Medical Corporation in the United States and/or other countries. Asahi Kasei is a registered trademark of Asahi Kasei Corporation. All other trademarks are the property of their respective owners. Respicardia and remede are trademarks of Respicardia, Inc. in the United States and/or other countries.

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