In the long standing debate over advanced, potentially more expensive, treatments for early-stage prostate cancer, a new study has recently been published in which five year outcomes data has been collected and reviewed for patients receiving CyberKnife prostate cancer treatment. As one of the early and most commonly treated indications on this platform, clinicians, patients, and professional societies have been long awaiting longer term outcome data. While the study, published in Radiation Oncology in January 2011, indicated that the therapy is both safe and effective based on a sample size of 41 low-risk prostate cancer patients, the study references the ideal need for larger and multi-center trials to continue to examine clinical outcomes.
Also noted in the study were a number of other trials slated to release five year outcomes data in the near future, run through a range of other early CyberKnife adopter institutions. Overall, there remains a lack of comparative data to put these treatment outcomes data into perspective, but this is often the case in radiation therapy. Furthermore, as these additional studies progress and the data mature, it is likely the industry will face a growing pool of data upon which to evaluate these treatments.
Meeting on January 20th, the Peripheral and Central Nervous System Drugs Advisory Committee of the FDA met to discuss potential approval for Amyvid, a novel radiotracer used to image beta amyloid plaque in the brain. Manufactured by Eli Lilly, Amyvid (florbetapir) is a PET radiotracer which binds to beta amyloid plaque, identified as an indicator of the progression of Alzheimer's disease. The Committee voted not to fully approve the new radiotracer, but rather, to give conditional approval should the manufacturer provide a sufficient training program for readers. Previous studies demonstrated significant variation in readers' ability to extract and interpret data, resulting in a high false-positive rate. The FDA is not calling for more research trials, but rather, that once a training program has been developed, the FDA will likely approve the radiotracer.
To date, the use of PET for neuroimaging has previously been challenging due to the lack of brain-specific radiotracers given existing limitations of using FDG-glucose. High metabolism in the brain renders standard glucose-based imaging unreliable, and PET has thus far been used primarily for oncologic imaging. Amyvid avoids this setback by binding directly to beta amyloid plaque, rather than tracking a specific metabolic process. While Amyvid will not likely be able to definitively diagnose Alzheimer's disease, it can confidently rule it out in favor of other neurodegenerative disorders.
While the availability of Amyvid marks an important step in the evolution of PET imaging to assess myriad neurodegenerative diseases, there is still uncertainty within the medical field regarding the value of detecting precursors to Alzheimer's disease. Without a valid treatment plan, questions remain as to the anxiety placed on the patient and their family in knowing that Alzheimer's is potentially impending. Confidently ruling out Alzheimer's can redirect physician attention to other diseases but detection of beta amyloid plaque does not always indicate Alzheimer's will be present. However, conditional approval of Amyvid and more widespread use of the neuro PET imaging agent can help to further answer these questions and determine an appropriate course of action.
Two-year trial results for Cook Medical's drug-eluting peripheral stent, Zilver PTX, were presented last week at the 23rd Annual International Symposium on Endovascular Therapy meeting in Miami Beach, FL. These findings follow the positive 12-month data presented at TCT in September of last year. The trial, which enrolled 478 patients with symptomatic, above-the-knee femoropopliteal disease, randomized patients to either treatment with the Zilver PTX stent or balloon angioplasty. Patients who experienced suboptimal angioplasty results (120) were then randomized a second time and treated with the Zilver PTX or the Zilver bare metal stent (BMS).
Expanding on the original Zilver bare-metal platform, the Zilver PTX represents the first drug-eluting stent of its kind. Although the self-expanding nitinol stent employs Paclitaxel, the drug used in the coronary drug-eluting stent (DES), TAXUS, it differs from coronary stents in that it is polymer-free, making it specially designed for use in the peripheral arteries.
In October, 12-month data showed that 90 percent of patients treated with the Zilver PTX achieved the safety endpoint--survival, free from amputation--versus 83 percent in the angioplasty group. These results dropped to 87 percent for the Zilver PTX group at 24 months. At both 12 and 24 months, the primary efficacy endpoint evaluated the patency rate for patients undergoing angioplasty or Zilver PTX in either randomization group. At 12 months in the first randomization group, the Zilver PTX, which displayed 83 percent patency, outperformed angioplasty, which only showed 33 percent patency. This trend continued to hold true for the second randomization group, with the Zilver PTX obtaining 90 percent patency versus 73 percent patency in the BMS group. At 24 months, the Zilver PTX continued to show positive outcomes, achieving 75 percent patency against angioplasty (for which 24-month data was unavailable), and 81 percent patency for the second randomization compared to the BMS group's 63 percent patency rate.
For Cook Medical, which hopes to receive FDA approval for the Zilver PTX stent in the near future, these findings show great promise for a strong market entrance and potentially beyond. As the first of its kind amidst a flurry of vascular devices released in recent years, the Zilver PTX's true market potential is not yet known. However, it could play a significant role as a standalone therapy. This is particularly true given the fact that, thus far, physician preferences, paired with the high costs of individual devices, have complicated cost-effective device management for many hospital administrators. To date, Cook has submitted its application to the FDA and is projecting approval in the next six to 12 months. Technology Insights will continue to track trial results and updates on this device.
Medtronic has received FDA approval to alter the design of its clinical trial for the transcatheter CoreValve device. CoreValve--an investigational device designed as an interventional alternative to traditional aortic valve replacement--is under evaluation in its pivotal FDA trial, which began enrolling patients in the past several weeks. With this announcement, the FDA has approved Medtronic's request to drop its randomization of patients receiving the device versus medical therapy in the inoperable cohort. The announcement comes on the heels of the positive results seen in the PARTNER trial studying Edwards LifeSciences' transcatheter SAPIEN device.
In September of last year, PARTNER researchers published extremely positive data for Cohort B of their pivotal trial. Cohort B randomized inoperable patients to either treatment with the transcatheter SAPIEN device or standard therapy. Data announced at TCT 2010 and published in the New England Journal of Medicine showed a 46 percent relative risk reduction in mortality for those patients receiving the device. Given that the CoreValve trial design was modeled off of PARTNER, many in the field expressed concerns about randomizing inoperable patients to an inferior therapy. The FDA has since examined PARTNER's data and subsequently decided to allow inoperable patients treated in the CoreValve trial to forgo randomization; instead, they will receive the device and be enrolled into a data registry. This decision is not only favorable for Medtronic's trial enrollment, but supports industry predictions that the SAPIEN device will receive initial approval late this year.
Patients enrolled in the CoreValve trial who are deemed high-risk for standard surgery will still undergo randomization in their cohort. This high-risk cohort will randomize patients to either treatment with the CoreValve device or standard surgical aortic valve replacement. Medtronic has started enrolling patients at a few of the 40 trial sites selected. Investigators hope to have the trial fully enrolled in 2012, a goal that is likely supported by this announcement.
Technology Insights will continue to monitor and provide updates regarding the trial.
Boston Scientific announced today that it will be purchasing Atritech, a company well known for making the "Watchman," a device for individuals with atrial fibrillation (AF) that is able to block the left atrial appendage, thus lowering the risk of clot formation and strokes in this patient population. The acquisition--totaling up to $375 million pending financial performance and regulatory approval by 2015--points to the Watchman's potential to aid a broad patient base and possibly serve as an alternative to anticoagulants for people with AF at high risk for ischemic strokes.
The 3 million people in the U.S. with AF, an arrhythmia causing irregular heartbeat, are often at increased risk for stroke because the heart's irregular contraction can lead to pooled blood and clots, particularly in the left atrial appendage. The Watchman works by blocking the opening between the left atrial appendage and the rest of the atrium, preventing clots in this area from dislodging into the bloodstream and causing a blockage. The device received CE Mark approval in 2009 and has already undergone the PROTECT-AF clinical trial that demonstrated a 38 percent reduced risk of stroke, cardiovascular death, and systemic embolism with the Watchman compared to patients on anticoagulants. However, in March of last year the FDA delayed the Watchman's approval requesting additional study of the device. The PREVAIL trial, expected to be the pivotal trial that could lead to the device's FDA approval, is currently enrolling patients.
Technology Insights will continue to follow updates to this trial and the progress of other novel devices in this space.
Today, the U.S. Preventive Services Task Force (USPSTF) issued updated guidelines for the screening of osteoporosis, a disease characterized by thinning bone tissue and loss of bone density. Osteoporosis overwhelmingly affects women, and accordingly, the guidelines recommend that all women over 65 and all women under 65 that have similar risk factors be screened routinely.
True to its name, the USPSTF's focused on enhancing screening with the aim of preventing acute events--in this case fractures. It's estimated that 1 in 2 women are at risk of an osteoporosis-related fracture during their lifetime, and with direct medical costs associated with these fractures estimated to be between $12.2 and $17.9 billion, the case for preventive care is strong. While no controlled studies have evaluated the effect of screening for osteoporosis on rates of fractures, early detection can reduce the risk of fractures.
As readers of this blog have seen recently, we've been especially interested in the role of disease management within musculoskeletal conditions, especially as it relates to expensive interventions such as joint replacement and spine surgery. With osteoporosis a leading cause of vertebral compression fracture that may require interventions (vertebroplasty, kyphoplasty) as well as hip fractures that may lead to hip replacement, the potential that more aggressive, early therapy could obviate the need for surgery is alluring.
From a strictly cost/benefit perspective, the role of early management can be difficult to justify. Often, the expense of the additional procedures--both the screenings and the resulting therapy--can more than offset the benefit of avoided surgeries (and may not avoid them anyway). With osteoporosis, the case may be a bit different: the imaging modalities used are basic, and therapy can often be dietary changes, exercise, and calcium supplements. The indirect benefits may be more substantial here, inasmuch as the therapy can improve the overall health of the patient, undoubtedly a major goal in disease management programs of care.
Last week, I blogged about the potential to take a more disease-management approach to osteoarthritis. The posting suggested that the maturity and clinical acceptance of joint replacement surgery may make osteoarthritis less of a priority as providers begin to develop new delivery models of care for chronic diseases.
In the past week, however, a new study emerged that may reawaken this conversation. Doctors from the University of Sydney in Australia and New England Baptist Hospital in Boston have just published a study in the American College of Rheumatology's journal, Arthritis Care & Research, that argues standard clinical practice often differs from the evidence based recommendations for the treatment of osteoarthritis (OA).
The authors suggest that current treatment patterns for OA do not aim at improvement in joint structure but rather aim to manage symptoms such as pain and joint function. Aggressive weight management and exercise programs can be incredibly beneficial and should be integral to the management of OA. The authors highlight that a high volume of unnecessary procedures--both surgical and ancillary such as imaging--are adding cost to an already burdened health care system, and that by more conservative wellness improvement, quality outcomes may be possible at a much lower cost.
These are important arguments to the health care debate, and will be welcome as researchers and practitioners work together to provide the best possible care without crippling the delivery system. We at Technology Insights are looking critically at the latest evidence available and speaking with leading programs constantly so that we can stay ahead of the curve on these exciting developments.
Abbott Vascular announced today that it received CE Mark approval for its drug-eluting bioabsorbable vascular scaffold (BVS), ABSORB. Approved in Europe to treat coronary artery disease, ABSORB will be the first of its kind available for commercial use. Like the traditional metal scaffold drug-eluting stents (DES), Abbott's ABSORB works to restore blood flow to a diseased vessel. However, unlike it's DES alternatives, the ABSORB stent slowly dissolves overtime leaving patients without a permanent metal implant.
ABSORB has previously demonstrated positive results both in the US and Europe, however, now with commercialization, cardiologists will have a therapeutic that enables them to restore natural vessel function without leaving a device in the body. This could mean that vessels treated with ABSORB have greater flexibility than those treated with traditional DES. More impactful however, will be research indicating the ability to reduce or stop long-term dual anti-platelet therapy (DAPT) for patients undergoing percutaneous coronary intervention. At present, following stent implantation, patients must follow a long-term DAPT regime; however, since the ABSORB trial dissolves the scaffold in the body, this could eliminate or greatly reduce this current requirement. Nevertheless, additional trials will be necessary to determine ABSORB's long-term potential as well as its potential effect on DAPT.
At present ABSORB will only be available to a handful of institutions in Europe with full European commercial approval expected by late 2012. To accommodate this, Abbott is launching a new clinical trial to study ABSORB in expanded indications. The study will enroll 500 patients at 40 European sites and will compare ABSORB to the currently available DES Xience PRIME, and Xience.
While ABSORB is not approved at present in the US, CE Mark often signals the first foray into the US market. It is likely that as adoption grows in Europe, US clinical trials will not be far behind.