FDA approved today the MicroTransponder Vivistim Paired VNS System, a first-of-its-kind, drug-free rehabilitation system intended to treat moderate to severe upper extremity motor deficits associated with chronic ischemic stroke using vagus nerve stimulation (VNS).
INBRAIN Neuroelectronics S.L. was funded in Barcelona, Spain in 2019 as a spin-off from Graphene Flagship partners, the Catalan Institute of Nanoscience and Nanotechnology (ICN2) and ICREA. Its subsidiary INNERVIA Bioelectronics is working towards the development and commercialization of graphene-based systems to modulate vagus nerve signals.
INBRAIN announced that it will be collaborating with Merck to co-develop the next generation of graphene bioelectronic vagus nerve therapies targeting severe chronic diseases in Merck’s therapeutic areas.
INBRAIN’s website is at: www.inbrain-neuroelectronics.com
LivaNova and Verily announced that they have enrolled their first patient in a study to evaluate treatment effectiveness for patients living with depression. From the press release:
“The first patient has been enrolled in their collaborative UNCOVER study or “The RECOVER Sub-Study, Which Leverages Quantitative and Credible Research Tools from Verily, Will Provide Assessment Measures for Depressive Episodes.”
The UNCOVER sub-study deploys technology-enabled research tools from Verily to evaluate the real-world effectiveness of VNS Therapy as an adjunctive treatment for difficult-to-treat depression (DTD).
Participants in the UNCOVER sub-study will use two Verily-developed digital tools – a wearable, multi-sensor device (Verily Study Watch) along with an Android smartphone application (Verily Mood App). The Verily tools measure passive and active data, such as the participant’s pulse rate, activity levels and sleep quality. The Mood App also allows participants to record voice diaries to more accurately assess depressive episodes and their effect on daily living.
Quantitative data obtained from these Verily tools will supplement the clinical outcomes collected in the RECOVER study, providing clinicians a more comprehensive view of whether each patient’s depression is improving, staying the same, or worsening.”
SetPoint Medical is a company based in Valencia, California developing an implantable-device-based therapy for chronic autoimmune diseases. It announced in May that it has received FDA IDE approval to study its device in patients with rheumatoid arthritis (RA).
The multicenter, double-blind, randomized, sham controlled pivotal trial will enroll up to 250 patients at 40 sites across the U.S. The trial will evaluate the safety and effectiveness of the SetPoint “microregulator” in patients with moderate-to-severe RA who are incomplete responders or are intolerant to biologic or targeted synthetic disease modifying anti-rheumatic drugs (DMARDs).
Back in July, 2005, the FDA approved Cyberonics (now LivaNova) VNS implant for patients with chronic or recurrent depression, either unipolar or bipolar, with a history of failure of the depression to respond to at least four antidepressant interventions.
However, the U.S. Centers for Medicare & Medicaid Services (CMS) declined covering VNS for serious depression. CMS concluded back in 2007 that VNS’ effectiveness was not compelling enough to expand coverage, leaving drug-resistant epilepsy as its only covered indication.
Ten years later LivaNova presented data from a five-year study of VNS for treating TRD which showed that patients with chronic moderate to severe TRD experienced anti-depressant effects at a significant rate when treated with the therapy.
In response, last month (February 2019) CMS said:
“Based on the evidence, we believe that VNS for TRD seems promising but not convincing.” “To ensure benefits to Medicare beneficiaries we are proposing to cover VNS for the treatment of TRD when offered in double-blind, randomized, placebo-controlled studies.”
Back in 2013 I reported about MicroTransponder’s Serenity System™, which pairs Vagus Nerve Stimulation (VNS) with listening to tones. During the therapy, an individual sits in a comfortable chair and wear headphones. They listen to tones while receiving small bursts of neurostimulation from the implantable vagus-nerve stimulator. UT Dallas says that “preclinical tests demonstrated that this approach “rewires” damaged brain circuitry associated with tinnitus, potentially yielding long-term reversal of symptoms. The initial human trial in Belgium provided encouraging results.”
More recently, MicroTransponder developed the Vivistim™ system intended for the treatment of stroke. The implant is based on the idea that synchronizing vagus nerve stimulation with movement increases neural plasticity in the brain, resulting in enhanced recovery.
In May 2017 MicroTransponder presented results from its Vivistim™ Stroke Rehabilitation trial. The objective of this multicenter, double-blind, randomized, active-controlled trial was to improve upper limb mobility in stroke survivors suffering chronic disability. The data showed 75% of patients had a clinically meaningful response on the Fugl-Meyer Upper Extremity Scale (FMUE) at the end of a six weeks of physical therapy compared to 33% for the control group. 90 days after the six weeks of physical therapy ended 88% of VNS patients had responded compared to 33% in the control arm. And during the long-term portion of the study average FMUE scores continued to increase, with the 6 month and 9 month data showing further gains. All responders indicated they believed their overall health had improved and were satisfied with the therapy.
At the same time, MicroTransponder announced that it had received IDE approval from the FDA to run a 120-patient pivotal trial on the Vivistim™ system.
MicroTransponders website: http://www.microtransponder.com
EnteroMedics reported new clinical trial data for its Maestro system, which is designed to treat obesity through vagus nerve stimulation. The company said that its Maestro RC system lost 25% of their excess weight, or 10% of their total body weight, after 18 months. Patients who received a sham implant lost 12% of excess weight, or 4% of their total weight. The company is running a five-year study of the system. The system is approved in Europe and Australia, but not the U.S.
Cerbomed GmbH, located in Erlangen, Germany, was founded in 2005 to develop transcutaneous Vagus Nerve Stimulation (t-VNS®) neuromodulation systems.
Surgically accessing the Vagus Nerve is not trivial, and implanting a VNS system involving cuff electrodes is risky and recovery is lengthy. Enter t-VNS, which is delivered non-invasively to the auricular branch of the vagus nerve (ABVN), making it an attractive therapy option when compared to implantable vagus nerve stimulators.
The NEMOS tVNS system consists of a handheld stimulator and a dedicated ear electrode, which patients wear like an earphone. According to Cerbomed, intensity, pulse duration and frequency of the t-VNS stimulation have been optimized to induce signals in thick-myelinated Aβ fibres of the ABVN. Like those of the cervical branch of the vagus nerve, these project directly to the nucleus of the solitary tract (NTS) in the brainstem.
In 2010 Cerbomed received the CE mark for its NEMOS® transcutaneous Vagus Nerve Stimulator for the treatment of epilepsy and depression. In 2012, the indication was expanded to include the treatment of pain.
In September 2012, Cerbomed entered into a strategic partnership with Cyberonics, Inc., the global market leader in vagus nerve stimulation. Cyberonics made an initial investment of €2 million to fund Cerbomed’s epilepsy clinical trial in Germany, with further investments of up to €5.5 million, subject to the achievement of certain clinical milestones. Cyberonics is a minority shareholder with certain rights, including representation on Cerbomed’s advisory board and an exclusive option for worldwide sales and distribution of NEMOS.
A position paper was published yesterday by the European Heart Rhythm Association reporting on the performance of new devices for the treatment of heart failure (HF). The report has been endorsed by the Heart Failure Association.
The abstract for the paper titled “New devices in heart failure: an European Heart Rhythm Association report” reads:
Several new devices for the treatment of heart failure (HF) patients have been introduced and are increasingly used in clinical practice or are under clinical evaluation in either observational and/or randomized clinical trials. These devices include cardiac contractility modulation, spinal cord stimulation, carotid sinus nerve stimulation, cervical vagal stimulation, intracardiac atrioventricular nodal vagal stimulation, and implantable hemodynamic monitoring devices. This task force believes that an overview on these technologies is important. Special focus is given to patients with HF New York Heart Association Classes III and IV and narrow QRS complex, who represent the largest group in HF compared with patients with wide QRS complex. An overview on potential device options in addition to optimal medical therapy will be helpful for all physicians treating HF patients.
The report places special focus to patients with HF New York Heart Association (NYHA) Classes III and IV and narrow QRS complex, who represent the largest group in HF compared with patients with wide QRS complex (who are candidates for treatment with cardiac resynchronization therapy – CRT).
MicroTransponder, Inc. of Dallas, TX has raised $3.4 million to carry out clinical trials of its Vivistim System to help restore functionality in the upper limbs of stroke patients, and its Serenity System designed to “rewire” the auditory cortex of tinnitus patients. The company intends to secure a CE mark for both systems next year, and then raise more funds to support a clinical trial for a pre-market approval in the U.S.
According to the company’s website, the Serenity System™ pairs Vagus Nerve Stimulation (VNS) with listening to tones. VNS is approved by the FDA and has been used to treat over 60,000 patients for epilepsy and depression, but has not yet been evaluated for safety or efficacy to treat tinnitus. The device is fully implantable and can easily be used at home. During the therapy, an individual sits in a comfortable chair and wear headphones. They listen to tones while receiving small bursts of neurostimulation, which activate the vagus nerve. UT Dallas says that “preclinical tests demonstrated that this approach “rewires” damaged brain circuitry associated with tinnitus, potentially yielding long-term reversal of symptoms. The initial human trial in Belgium provided encouraging results.”
Surgically accessing the Vagus Nerve is not trivial, and implanting a VNS system involving cuff electrodes is risky and recovery is lengthy. Enter ElectroCore Medical of Bernards Township, New Jersey – it is developing non-invasive VNS therapies that treat or prevent symptoms of serious headache conditions, including migraines and cluster headaches, and bronchoconstriction including asthma and chronic obstructive pulmonary disorder (COPD).
Its gammaCore® therapy is applied using a hand-held, non-invasive neurostimulator device, and is used to treat primary headaches in adults, including migraine, cluster headache, and medication overuse headache. According to ElectroCore, “gammaCore relies on the activation of afferent A-fibers in the vagus nerve which is not implicated in negative cardiac or respiratory effects.” Results from studies of the therapy as both an acute and preventative against these headache types have been promising, and are ongoing around the world.
I found online the PowerPoint presentation for: R Zitnik, Y Levine, M Faltys, T Arnold, “Harnessing the Inflammatory Reflex: Using Neuromodulation as a Novel Approach to Treat Chronic Inflammatory Diseases”, North American Neuromodulation Society Meeting 2012.
The presentation shows some preliminary animal results, presents an artist’s conception of the implantable system, and concludes as follows:
“- Inflammatory diseases are a $30B market with significant unmet need
– Using neuromodulation to drive the inflammatory reflex has a sound biological foundation: Use in clinic is supported by strong preclinical evidence
– This is the first demonstration that an implantable neuromodulation device improves clinical manifestations of RA:
- Significant and clinically meaningful improvement in signs and symptoms
- Response rates were comparable to those with current biologic agents
- Further larger controlled studies in RA and other chronic inflammatory diseases are warranted.
- Our microregulator offers significant advantages over current vagal nerve stimulation devices
SetPoint intends to offer a novel therapy that will significantly increases patient QOL, while bending per-patient cost curves down by more than 60%”
Net product sales increased 12.4% to $67.4 million in the first fiscal quarter ended July 26 for Cyberonics, Inc. of Houston, TX. Including license revenue, sales were up 14.2% overall, with Europe in particular contributing a strong performance. Diluted earnings per share were adjusted by $0.17 cents due to a litigation settlement.
According to the Aug. 22, 2013 press release, “operating results for the first quarter of fiscal 2014 compared to the first quarter of fiscal 2013, and other achievements, include:
- Net product sales of $67.4 million, an increase of 12.4%;
- Net sales of $68.9 million (including $1.5 million of license revenue), an increase of 14.2%;
- Worldwide unit sales of 3,354, an increase of 9.8%;
- Record U.S. net product sales of $56.4 million, an increase of 10.8%;
- Strong International unit sales of 899, an increase of 20.8%;
- Adjusted non-GAAP income from operations increased by 21.9% to $21.0 million and adjusted non-GAAP income per diluted share increased by 27.9% to $0.48;¹
- Share repurchases of $13 million; and
- Significant progress in three clinical studies, E-36, E-37, and ANTHEM.”
SetPoint Medical, headquartered in Valencia, California, is developing neuromodulation therapies for patients with inflammatory autoimmune diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), psoriasis, diabetes, heart disease, and multiple sclerosis. SetPoint’s proprietary neuromodulation platform consists of an implantable “microregulator”, wireless charger and iPad prescription pad application.
SetPoint announced today that it has secured $27 million in financing from its current investors along with new investors Covidien Ventures, Action Potential Venture Capital Limited, the new GlaxoSmithKline (GSK) strategic venture capital fund for bioelectronic medicines and technologies, and Boston Scientific. The proceeds of the financing will be used to expand ongoing clinical development of the SetPoint bioelectronics therapy approach in rheumatoid arthritis and Crohn’s disease and advance development of the SetPoint proprietary neuromodulation platform.
In June 2012 Neurotech s.a. (http://www.neurotech-int.eu), a Belgium based developer and manufacturer of neurostimulation devices, obtained the CE Mark for its ADNS-300 system for the treatment of refractory epilepsy. According to the press release:
“Advens therapy” uses the ADNS-300 stimulator as a therapeutic option for those patients who are refractory to anti-epileptic drugs and are not eligible for epilepsy (brain) surgery. The ADNS-300 is the world’s first rechargeable neurostimulator for vagus nerve stimulation. The device includes an innovative electrode and a promising “sensing” feature that may prove to be a significant technological breakthrough in the control of response to the therapy. Patients use a remote controller and charger to turn the system on/off and to recharge the neurostimulator. “Rechargeable systems may prove to be more cost-effective, especially if surgical operations to replace batteries are avoided over time. This helps patients to maintain a more independent life, with a lower risk of potential complications associated with battery replacement surgery.” ‘The role of Rechargeable Systems in Neuromodulation Paul Eldridge et al.’