About LivaNova PLC

LivaNova PLC operates as a global medical device company. The company designs, develops, manufactures and sells products and therapies that are consistent to provide hope for patients and their families through innovative medical technologies, delivering life-changing improvements for both the Head and Heart. Segments The company operates through three segments: Cardiopulmonary, Neuromodulation, and Advanced Circulatory Support. Cardiopulmonary segment Cardiopulmonary segment engages in the development, production and sale of cardiopulmonary products, including heart-lung machines (HLM), oxygenators, autotransfusion systems, perfusion tubing systems, cannulae and other related accessories. It includes the development of the Essenz Perfusion System, the company’s next-generation HLM and a patient monitor that delivers a patient-tailored approach, supporting data-driven decisions during cardiopulmonary bypass procedures. In the fourth quarter of 2022, the company completed the first clinical cases using Essenz in two major centers in Europe. Cardiopulmonary bypass is commonly used in many operations involving the heart. The technique enables the surgical team to oxygenate and circulate the patient's blood, thus allowing the surgeon to operate on the heart. The most commonly performed procedures requiring cardiopulmonary bypass are conventional coronary artery bypass grafting and valve surgeries. In such procedures, the patient is placed on an extracorporeal circulatory support system that temporarily functions as the patient’s heart and lungs and provides blood flow to the body. The company’s products include systems to enable cardiopulmonary bypass, including HLMs, oxygenators, autotransfusion systems, perfusion tubing sets, cannulae and accessories, as well as related equipment and disposables for autotransfusion and autologous blood washing for neonatal, pediatric and adult patients. The company’s primary cardiopulmonary products include: Heart-Lung Machines: The HLM product group includes HLMs, heater coolers, related cardiac surgery equipment and maintenance and technical services. HLMs temporarily take over the work of the heart and/or lungs, providing blood and oxygen to the body. HLMs are most often used during serious procedures that require the heart to be stopped. Heater coolers are used during surgeries to warm or cool patients as part of their care. They are especially important during surgeries involving the heart and lungs. Oxygenators and Perfusion Tubing Systems: The oxygenators product group, which includes oxygenators and other disposable devices for extracorporeal circulation, includes the Inspire systems. The Inspire range of products consist of 12 models and provides perfusionists with a customizable approach for the benefit of patients. Oxygenators exchange oxygen and carbon dioxide in the blood of patients during surgical procedures. An oxygenator is typically utilized by perfusionists during cardiac surgery in conjunction with a HLM. Oxygenators can also be utilized in extracorporeal membrane oxygenation (ECMO). Autotransfusion Systems: One of the key elements for a complete blood management strategy is autologous blood transfusion. The autotransfusion product group facilitates the collection, processing and reinfusion of the patient’s own blood lost at the surgical site. Cannulae: The company’s cannulae product family is used to connect the extracorporeal circulation to the heart of the patient during cardiac surgery. Neuromodulation segment Neuromodulation segment engages in the design, development and marketing of devices that deliver neuromodulation therapy for treating drug-resistant epilepsy (DRE) and difficult-to-treat depression (DTD). It also encompasses the development and management of clinical testing of its aura6000 System for treating obstructive sleep apnea (OSA) and, until recently, the company’s VITARIA System which was intended to treat heart failure. The company’s principal Neuromodulation product, the LivaNova Vagus Nerve Stimulation Therapy (VNS Therapy) System, is an implantable device authorized for the treatment of DRE and DTD. The VNS Therapy System consists of an implantable pulse generator and connective lead that stimulate the vagus nerve; surgical equipment to assist with the implant procedure; equipment and instruction manuals enabling a treating physician to set parameters for a patient’s pulse generator; and for epilepsy, magnets to manually suspend or induce nerve stimulation. The pulse generator and lead are surgically implanted in a subcutaneous pocket in the upper left chest area, generally during an out-patient procedure. The lead, which does not need to be removed to replace a generator with a depleted battery, is connected to the pulse generator and tunneled under the skin to the vagus nerve in the lower left side of the patient’s neck. The company’s aura6000 device for treating OSA stimulates the hypoglossal nerve, which in turn, engages certain muscles in the tongue to open the airway while a patient is sleeping. Epilepsy There are several broad types of treatment available to patients with epilepsy: multiple anti-seizure medications (ASMs); various forms of the ketogenic diet; vagus nerve stimulation (VNS); resective and ablative brain surgery; and intracranial neurostimulation. ASMs typically serve as a first-line treatment and are prescribed for virtually all patients diagnosed with epilepsy. After two anti-seizure medications fail to deliver seizure control, the epilepsy is characterized as drug-resistant, at which point, adjunctive non-drug options are considered, including VNS therapy, ketogenic diet, resective or ablative surgery and other neuromodulation therapies. The company’s VNS Therapy System was the first medical device treatment approved by the FDA for the treatment of drug-resistant epilepsy, and today is the only neuromodulation device approved for use in DRE patients in the U.S. as young as four years of age with partial onset, or focal, seizures. Other worldwide regulatory bodies have also approved the VNS Therapy System for treating patients with DRE, many without age or seizure-type restrictions. Globally, VNS Therapy is the most widely reimbursed neuromodulation therapy available. In 2020, the U.S. Centers for Medicare and Medicaid Services (CMS) expanded reimbursement for VNS Therapy use in the treatment of Dravet Syndrome and, in January 2022, expanded reimbursement for VNS Therapy use in the treatment of Lennox Gastaut Syndrome. The company distributes multiple VNS Therapy Systems for the treatment of epilepsy, including Model 103 (Demipulse), Model 104 (Demipulse Duo), Model 106 (AspireSR), Model 1000 (SenTiva) and Model 1000D (SenTiva Duo) pulse generators. The company’s AspireSR and SenTiva generators provide the traditional benefits of VNS Therapy but add an additional stimulation capability: closed loop stimulation (AutoStim) which responds to detection of changes in heart rate potentially indicative of a seizure. The SenTiva generator is the smallest and lightest VNS device capable of delivering responsive therapy for epilepsy and includes the additional flexibility of its Scheduled Programming and Day & Night Programming capabilities. In 2017, VNS Therapy devices were FDA approved for expanded magnetic resonance imaging (MRI) access while similar CE Mark approval followed shortly thereafter. SenTiva, AspireHC and AspireSR models of VNS Therapy technology provide for this expanded MRI access. Depression In 2005, the FDA approved the VNS Therapy System for the adjunctive treatment of chronic or recurrent depression for patients 18 years or older who are experiencing a major depressive episode and have not had an adequate response to four or more antidepressant treatments. In 2007, the United States (U.S.) CMS issued a national non-coverage determination (NCD) within the U.S. with respect to reimbursement of the VNS Therapy System for patients with DTD, significantly limiting access to this therapeutic option for most patients. In 2020, the company’s VNS Therapy System, Symmetry received CE mark approval for the treatment of DTD. In 2019, CMS produced a final decision providing coverage for Medicare beneficiaries through Coverage with Evidence Development (CED) when offered in a CMS-approved, double-blind, randomized, placebo-controlled trial with a follow-up duration of at least one year, as well as coverage of VNS Therapy device replacement. The CED also includes the possibility to extend the study to a prospective longitudinal registry. In 2019, CMS accepted the protocol for the company’s RECOVER clinical study and the first patient was enrolled. RECOVER may include up to 500 unipolar and up to 500 bipolar patients at a maximum of 100 sites in the United States in the randomized part of the trial and may include up to an additional 5,800 patients in an open label registry. In 2020, the company announced a research collaboration with Verily, a subsidiary of Alphabet Inc., to capture clinical biomarkers of depression within its RECOVER clinical study. Using technology and analytics by way of the Verily Study Watch and related Verily mobile phone application, LivaNova and Verily aim to gather quantitative data to further understand depressive episodes and a patient’s response to treatment. In March 2022, LivaNova announced the 250th unipolar depression patient was implanted in the RECOVER clinical study. This key milestone preceded conducting the first interim analysis. The study was designed with frequent interim analyses, which occur every 25 patients, to be conducted by an independent Statistical Analysis Committee. The interim analysis assesses if predictive probability of success has been reached for the unipolar cohort of the study, at which point the randomized controlled trial (RCT) enrollment will cease and future patients will be enrolled into the prospective open label longitudinal study for that cohort. Obstructive Sleep Apnea In 2018, the company acquired full ownership of ImThera, a privately held, emerging-growth company developing an implantable neurostimulation device system for the treatment of obstructive sleep apnea. The device stimulates the hypoglossal nerve, which in turn, engages certain muscles in the tongue in order to open the airway while a patient is sleeping. Heart Failure The VITARIA System was intended to treat heart failure through VNS. In 2018, after completion of pilot studies outside the U.S., the company announced the first successful implantation of the VITARIA System in a patient randomized in the ANTHEM-HFrEF clinical trial, an international, multi-center, randomized trial (adaptive sample size) to evaluate the VITARIA System for the treatment of advanced heart failure. During the fourth quarter of 2022, the company randomized the 500th patient in the trial which triggered the second interim analysis. The independent Data and Safety Monitoring Committee (DSMC) evaluated safety, a trend toward the primary endpoint and success in the three functional endpoints. This analysis determined that the U.S. FDA early filing conditions were not met, and the DSMC recommended that enrollment continue in accordance with the current study protocol. However, the company conducted further evaluation of the study data and concluded that such data did not demonstrate a sufficiently strong positive impact on functional or mortality endpoints and that it was unlikely that the continuation of the study would demonstrate such an impact. As a result, on February 22, 2023, it announced that the company is stopping enrollment in the ANTHEM-HFrEF clinical trial, beginning the process to close the clinical study and winding down its heart failure program. Advanced Circulatory Support segment ACS segment engages in the development, production and sale of leading-edge temporary life support products. The company’s ACS products, which include the LifeSPARC platform and ProtekDuo cannula, simplify temporary extracorporeal cardiopulmonary life support solutions for critically ill patients. The LifeSPARC platform includes a common compact console and pump that provides temporary support for emergent rescue patients in a variety of settings. Designed for ease of use, the system offers power and versatility for multi-disciplinary programs to support more patients in more places. The platform is accompanied by four specialized and ready-to-deploy kits, each designed to support diverse cannulation strategies. In November 2022, the FDA approved the company’s LifeSPARC platform for extracorporeal membrane oxygenation (ECMO). This approval allows for the company’s LifeSPARC platform to be used for ECMO beyond six hours for patients in acute respiratory failure or acute cardiopulmonary failure, including but not limited to those receiving treatment for COVID-19. The company previously owned a 3% equity interest in ALung Technologies, Inc. (ALung), a privately-held medical device company focused on creating advanced medical devices for treating respiratory failure. In May 2022, the company acquired the remaining 97% of equity interests. In August 2022, CMS approved a New Technology Add-on Payment (NTAP) for the company’s Hemolung RAS for in-patient care. The NTAP designation is awarded to novel medical technologies and services supported by clinical evidence that are expected to substantially improve the diagnosis or treatment of Medicare beneficiaries. Patents and Licenses The company generally files patent applications in the U.S. and countries where patent protection for its technology is appropriate and available. As of December 31, 2022, the company held more than 840 issued patents worldwide, with approximately 285 pending patent applications that cover various aspects of its technology. Patents typically have a 20-year term from the application filing date. In addition, the company holds exclusive and non-exclusive licenses to a variety of third-party technologies covered by patents and pending patent applications. Markets and Distribution Methods The three largest markets for the company’s medical devices are the U.S., Europe and the Asia-Pacific region (APAC). The company sells most of its medical devices through direct sales representatives in the U.S. and a combination of direct sales representatives and independent distributors in markets outside the U.S. The company’s marketing and sales strategy is focused on rapid, cost-effective delivery of high-quality products to a diverse group of customers worldwide, including perfusionists, neurologists, neurosurgeons and other physicians, hospitals and other medical institutions and healthcare providers. The company maintains a highly knowledgeable and dedicated sales staff that is able to foster strong relationships with its broad range of customers. The company cultivates and maintains close working relationships with professionals in the medical industry. These relationships provide the company with a detailed understanding of therapeutic and diagnostic developments, trends and emerging opportunities, which enable it to respond to the changing needs of providers and patients. The company actively participates in medical meetings and conduct comprehensive training and educational activities to enhance its presence in the medical communities it serves. Competition The company’s primary medical device competitors in the Cardiopulmonary, Neuromodulation and Advanced Circulatory Support product groups are Terumo Medical Corporation, Maquet Medical Systems, Medtronic plc, Haemonetics Corporation, NeuroPace, Inc. and Abbott Laboratories, Inc., although not all competitors are present in all product lines. Seasonality The number of medical procedures incorporating the company’s products is generally lower during the summer months, particularly in European countries, due to summer vacation schedules. Government Regulation and Other Considerations Each medical device the company seeks to distribute commercially in the U.S. must receive 510(k) clearance or pre-market approval (PMA) from the FDA, unless specifically exempted by the agency. The 510(k) process, also known as pre-market notification, requires the company to demonstrate that its new medical device is substantially equivalent to a legally marketed medical device. The PMA process, which is more costly and rigorous than the 510(k) process, requires the company to demonstrate independently that a medical device is safe and effective for its intended use. The company’s worldwide business is subject to the U.S. Foreign Corrupt Practices Act of 1977 (the FCPA), the UK Bribery Act of 2010 (the UK Bribery Act), and other anti-corruption laws and regulations applicable in the jurisdictions where it operates. History LivaNova PLC was founded in 1987. The company was incorporated in 2015.