Peripheral artery disease (PAD), a circulatory condition in which narrowed arteries reduce blood flow to the extremities, is projected to affect over 21 million patients in the United States by 2020. Common treatments include balloon angioplasty, atherectomy, stenting, and bypass, all of which require physicians to use tools which enter the patients arteries in order to address the build up of arterial plaque. In order to guide the physician during these procedures, imaging techniques like fluoroscopy, which use X-rays, help to track the position of medical devices within the patient while tactile feedback is used to make sure the intervention is being applied in the right location. While this is the state of the art today, the use of fluoroscopy exposes both patients and clinicians to radiation while providing very limited visibility to the work area.
To address these challenges and completely revamp the concept of imaging during PAD treatment is medical device company Avinger. The California-based business has developed the Lumivascular Platform which includes a suite of technologies representing the world’s only real-time, intravascular imaging technology to allow direct visualization within the artery during PAD treatment using optical coherence tomography (OCT). This approach is radiation free and, for the first time, allows direct visualization of the arterial lumen in the vicinity of the device during surgery. Clinical studies have already shown excellent patient outcomes and an improvement in treatment side effects such as adventitial disruption (1% in the Avinger VISION trial compared to 53% with traditional atherectomy).
To learn more about Avinger and the company’s growing suite of technologies, Medgadget had a chance to connect with CEO and President Jeff Soinski.
Michael Batista, Medgadget: What are the common treatment options for PAD today?
Jeff Soinski: There are a wide variety of treatments currently used for the treatment of PAD, ranging from highly invasive bypass surgery to minimally invasive endovascular treatments, such as balloon angioplasty, the placement of stents, and atherectomy, which is the use of a catheter-based device for the removal of plaque.
Medgadget: How do physicians normally navigate a patient’s arteries in order to conduct these procedures?
Soinski: Physicians treating PAD with current non-imaging devices must rely solely on X-ray (fluoroscopy) as well as tactile feedback to guide their interventions while treating complicated arterial disease. They have no means of visualizing inside the vessel to discriminate between diseased tissue and the healthy arterial structures during treatment.
Medgadget: What are the limitations of current approaches to treating PAD and the imaging techniques they employ?
Soinski: Current treatments all have limitations in their safety or efficacy profiles and frequently result in recurrence of the disease, also known as restenosis. We believe one of the main contributing factors to high restenosis rates for PAD patients treated with endovascular technologies is the amount of vascular injury that occurs during an intervention.
Medgadget: What has Avinger developed to address these challenges and what sets Avinger’s technologies apart from the competition?
Soinski: Our Lumivascular platform is the only technology that offers real-time visualization of the inside of the artery during PAD treatment through the use of optical coherence tomography (OCT), a high resolution, light-based, radiation-free imaging technology. Our Lumivascular platform provides physicians with real-time OCT images from the inside of an artery that are displayed on our proprietary Lightbox imaging console during treatment. Our Ocelot and Pantheris image-guided catheters are the first products to offer intravascular visualization during chronic total occlusion (CTO) crossing and atherectomy, respectively. We believe this approach will significantly improve patient outcomes by providing physicians with a clearer picture of the artery during treatment, enabling them to better differentiate between plaque and healthy arterial structures. Our Lumivascular platform is designed to improve patient safety by enabling physicians to direct treatment towards the plaque, while avoiding damage to healthy portions of the artery.
Medgadget: What are Avinger’s unique technology innovations or insights that has allowed the company to push the technology envelope for PAD treatment?
Soinski: The major innovation driving our unique approach to the treatment of PAD is the combination of real-time intravascular imaging with highly effective therapeutic catheters in a single device. This represents a tremendous technological hurdle given the small size requirements for the devices and the need for the image to be captured at the point of interaction between the vessel and the therapeutic catheter. Our catheters are also designed to provide precise control by physicians during a therapeutic procedure, so they can provide their patients with the full benefit of the information provided by real-time intravascular imaging during treatment. We are not aware of any other company that has developed or is close to developing endovascular therapies for the treatment of PAD that combine real-time intravascular imaging via OCT or any other imaging modality with therapeutic catheters in a single device.
Medgadget: Avinger’s technologies have been used in a number of clinical trials. Can you share some highlights of those studies?
Soinski: The clinical trial for Avinger’s Ocelot device, known as CONNECT II, was a prospective, multi-center, non-randomized trial that evaluated the safety and efficacy of Ocelot in crossing chronic total occlusions (CTOs) or a complete blockage in arteries of the upper leg using OCT intravascular imaging. The CONNECT II trial enrolled 100 patients with CTOs at 14 centers in the United States and two centers in Europe. Patients were followed for 30 days post-procedure and an independent group of physicians verified the results to confirm the primary efficacy and safety endpoints. Results from the CONNECT II trial demonstrated that Ocelot surpassed its primary efficacy endpoint by successfully crossing the CTO in 97% of the cases following unsuccessful attempts to cross with standard guidewire techniques. Ocelot exhibited an excellent safety profile and achieved these rates with 98% freedom from major adverse events (MAEs). We are not aware of any other published studies that delivered more positive results than Ocelot in the CONNECT II study.
VISION was our pivotal, non-randomized, prospective, single-arm trial to evaluate the safety and effectiveness of Pantheris across 20 sites within the United States and Europe. The objective of the clinical trial was to demonstrate that Pantheris can be used to effectively remove plaque from diseased lower extremity arteries while using on-board visualization as an adjunct to fluoroscopy. Two groups of patients were treated in VISION: (1) optional roll-ins, which are typically the first two procedures at a site, and (2) the primary cohort, which are the analyzable group of patients. Based on final enrollment, the primary cohort included 130 patients.
VISON’s primary efficacy endpoint required that at least 87% of lesions treated by physicians using Pantheris have a residual stenosis of less than 50%, as verified by an independent core laboratory. The primary safety endpoint required that less than 43% of patients experience an MAE through six-month follow-up as adjudicated by an independent Clinical Events Committee, or CEC. MAEs as defined in VISION included cardiovascular-related death, unplanned major index limb amputation, clinically driven target lesion revascularization, or TLR, heart attack, clinically significant perforation, dissection, embolus, and pseudoaneurysm. Results from the VISION trial demonstrated that Pantheris surpassed its primary efficacy and safety endpoints; with residual restenosis of less than 50% achieved in 96.3% of lesions treated in the primary cohort.
Although not mandated by the FDA to support the market clearance of Pantheris, the protocol for the VISION trial allowed for routine histopathological analysis of the tissue extracted by Pantheris to be conducted. This process allowed us to determine the amount of adventitia present in the tissue, which in turn indicated the extent to which the external elastic lamina had been disrupted during Pantheris procedures. We completed histopathological analysis on tissue from 129 patients in the primary cohort, representing 162 lesions and determined that the average percent area of adventitia was only 1.0% of the total excised tissue. We believe the low level of EEL disruption will correlate to lower restenosis rates and improved long-term outcomes for patients treated with Pantheris. We published the results of the histopathological analysis in conjunction with the primary safety and efficacy endpoint data from the VISION trial.
Although the original VISION study protocol was not designed to follow patients beyond six months, in 2016 we began working with 18 of the VISION sites to re-consent patients in order for them to be evaluated for patient outcomes through 12 and 24 months following initial treatment. Data collection for patients from participating sites was completed in May 2017, and we released the final 12- and 24-month results for a total of 73 patients and 89 lesions in July 2017. The key metrics reported for this group were freedom from target lesion revascularization, or TLR, at 12 months and 24 months, which were 82% and 74% by patient and 83% and 76% by lesion, respectively, based on Kaplan-Meier curve assessments, extremely positive results compared to those achieved in studies for other non-imaging atherectomy devices.
Medgadget: What are some of the next steps for Avinger’s different product lines?
Soinski: We have a number of important product and clinical milestones to look forward to in 2018 with the objective of continuing to advance and develop our Lumivascular platform and products and continuing to build the body of clinical evidence in support of our Lumivascular approach to the treatment of PAD.
In December 2017, we submitted a 510(k) application for clearance of a next generation Pantheris image-guided atherectomy catheter, which incorporates a number of new features and improvements, and are hopeful that we will receive FDA clearance to allow for introduction of this improved device into the U.S. market in the first half of this year. We received CE-marking for the next generation Pantheris device in December and have physicians in Europe have been reporting extremely positive clinical experience with this new device since that time.
In addition, we expect to submit a 510(k) application for clearance of a lower profile version of Pantheris for smaller vessels, including those below-the-knee, by mid-year 2018. We expect to receive CE-marking for this new device around the same time we file our 510(k) in the US, which would provide the opportunity for early clinical experience with this new lower-profile device in Europe soon after filing. We are excited about the prospects for this important new expansion of our Pantheris product line, since we believe our outstanding safety profile and the information provided by real-time imaging inside the artery will be critical differentiators for the treatment of smaller vessels, especially those below-the-knee.
Medgadget: What about Avinger’s Ocelot technologies?
Soinski: Our R&D team has also made excellent progress in the development of our next generation CTO-crossing device. Our Ocelot family of catheters are the only image-guided CTO-crossing catheters on the market, and have some of the strongest clinical data ever recorded for a CTO-crossing device with 97% success in crossing CTOs in peripheral arteries and 98% freedom from major adverse events in the 100-patient CONNECT II study, which supported Ocelot’s FDA clearance in 2012. This more mature product line is highly reliable and continues to deliver strong clinical results every day, and remains an important contributor to our Lumivascular franchise. However, we see an opportunity to improve and expand this platform with a next generation device, which we are calling Ocelaris.
Ocelaris will have faster rotation speeds and a unique “steerable” proprietary tip design, which we expect to result in even higher-definition real-time imaging and enhanced CTO-crossing capability in a variety of lesion types. This new catheter is also expected to feature a low-profile design, which would be suitable for use in smaller vessels, including those below-the-knee. We anticipate completing development of this next generation device in 2018 and submitting a 510(k) application for use in the peripheral arteries prior to the end of this year.
Medgadget: You’ve already had some excellent clinial trial results, are any others underway or on the horizon?
Soinski: In October 2017, we announced that we began enrollment of our INSIGHT IDE trial, our pivotal clinical study to evaluate the safety and effectiveness of Pantheris in treating in-stent restenosis, or ISR. While Pantheris is not contraindicated for ISR, the results of this study are intended to support a 510(k) submission with the FDA to expand the Pantheris product label to specifically include the ISR indication, which would enable us to directly promote Pantheris for this purpose in the US. We are optimistic about Pantheris’ potential role in this challenging area, which represents approximately 20% of PAD procedures in the US. Our trial is approved for up to 140 patients at up to 20 sites. We expect most of the enrollment in this trial to take place once the next generation Pantheris is commercially available in the US, and plan to complete enrollment of the INSIGHT trial this year.
Medgadget: With all that product development and enhancement, there’s a lot on your plate! Are there any other important initiatives Avinger is engaged with that you’d like to share?
Soinski: In addition to our product development and clinical activities, we also have important reimbursement initiatives underway. We plan to file an application for a new CPT code for OCT diagnostic reimbursement by the end of the second quarter. Our goal is to gain incremental reimbursement for OCT diagnostic imaging for our devices in the peripheral arteries, similar to the reimbursement currently provided for the use of intravascular ultrasound or IVUS in this setting. While the FDA has already cleared OCT diagnostic claims for our Pantheris and Ocelot devices, we anticipate that this CPT application would be supported by a small scale clinical trial, which we are in the process of initiating here in the US, that compares OCT diagnostic imaging to IVUS in the peripheral arteries. Strong reimbursement already exists for atherectomy procedures in the peripheral arteries – reimbursement that our Pantheris device already qualifies for. If we are successful in obtaining this new CPT code for OCT diagnostic reimbursement, we expect it would be incremental to current reimbursement levels, and we anticipate the new code would apply to any of our Lumivascular devices – Pantheris, Ocelot or future OCT image-guided products.
Medgadget: Finally, you’ve highlighted how Avinger’s technology is radiation free. Radiation is not just a concern for patients but also for the physicians conducting procedures on patients. Can you comment on the challenge of radiation exposure to physicians and how Avinger is addressing the issue?
Soinski: During a typical catheter lab procedure, X-ray scanning is performed to guide the physician and technologists. For the patient, this may amount to insignificant radiation exposure. However, the physicians and healthcare workers in the catheter lab environment do not leave the lab after one patient. For them, the process repeats itself – often for many years. They are exposed to more radiation in a single week than a patient might receive in their lifetime and there is growing evidence that this has associated physical risks (see image below). However, through the use of Lumivascular catheters with real-time optical coherence tomography (OCT) guidance, physicians have an opportunity to reduce their utilization of fluoroscopy/radiation without having to sacrifice their view of the patient’s anatomy. In fact, the OCT image may provide more information about the patient than other imaging modalities. See more, radiate less: that’s the goal of Lumivascular Image Guided Therapy.
Flashbacks: Avinger Ocelot Catheter with Optical Coherence Tomography Cleared by FDA for PAD…; Avinger’s New Pantheris OCT Image Guided Atherectomy Device Cleared by FDA…; Avinger’s Wildcat Catheter for Crossing Chronic Total Occlusions in PAD…
Link: Avinger homepage…