HOFFMAN ESTATES, Ill. -- Siemens Healthcare (NYSE: SI) is the first company worldwide to announce a complete integrated diagnostic imaging solution proposed for the detection of amyloid plaques -- one of the necessary pathological features of Alzheimer's disease(1,2,3) -- in the living brain. The latest elements of Siemens' integrated solution came today with the company's U.S. Food and Drug Administration (FDA) 510(k) application for its syngo(®).PET Amyloid Plaque(4) proprietary neurology quantification software, as well as the recent FDA approval of Eli Lilly and Company's Amyvid(TM) (Florbetapir F 18 Injection), a radioactive diagnostic agent indicated for brain imaging of beta-amyloid plaques in patients with cognitive impairment who are being evaluated for Alzheimer's disease and other causes of cognitive decline.(5)
Siemens integrated amyloid imaging solution encompasses three unique elements -- the new Biograph mCT(TM) PET-CT scanner, FDA 510(k)-pending syngo.PET Amyloid Plaque neurology quantification software and the manufacturing and distribution of Amyvid. All are examples of Siemens Healthcare's innovative power and competitiveness, which are two goals of the company's global initiative, Agenda 2013.
As the largest producer and distributor of Amyvid, PETNET Solutions, Siemens' network of PET drug manufacturing establishments, will begin supplying Amyvid to imaging centers in limited U.S. markets beginning in June 2012. Complementing the new radioactive diagnostic agent, Siemens pending software could potentially support the quantification of amyloid plaque in the brain. Combined with the company's family of high-resolution PET imaging scanners, Siemens now announces for the first time an integrated diagnostic tool for patients with cognitive impairment who are being evaluated for Alzheimer's disease and other causes of cognitive decline.
"Siemens is proud to be the first and only company to implement an integrated solution to support the evaluation of Alzheimer's disease and other causes of cognitive decline," said Britta Fuenfstueck, CEO of Molecular Imaging, Siemens Healthcare. "The combination of reliable manufacturing and distribution of Amyvid with Siemens' new Biograph mCT PET-CT and our pending syngo.PET Amyloid Plaque neurology quantification software will give physicians in the U.S. additional tools for the evaluation of Alzheimer's disease and other neurologic conditions."
A negative Amyvid scan indicates sparse to no amyloid plaques are currently present, which is inconsistent with a neuropathological diagnosis of Alzheimer's disease and reduces the likelihood that a patient's cognitive impairment is due to Alzheimer's disease.(1,6)( )A positive Amyvid scan indicates moderate to frequent amyloid plaques are present; this amount of amyloid plaque is present in patients with Alzheimer's disease, but may also be present in patients with other types of neurologic conditions and in older people with normal cognition.(3, 5, 7)
It is important to note that Amyvid is an adjunct to other diagnostic evaluations. A positive Amyvid scan does not establish a diagnosis of Alzheimer's disease or other cognitive disorder. Additionally, the safety and effectiveness of Amyvid have not been established for predicting development of dementia or other neurologic condition, or monitoring responses to therapies.(5)
Amyvid images should be interpreted only by readers who successfully complete a special training program, which will be provided by Lilly.
Siemens PETNET Solutions to supply Amyvid to imaging centers across the U.S.
The combination of higher purity demands and the complex nature of F-18 amyloid imaging compounds introduces the need for rigorous purification techniques, as well as new manual and automated manufacturing steps. As a result, the standard manufacturing process for novel, non-traditional imaging biomarkers presents greater opportunity for failure and consequently lower delivery reliability compared with traditional PET radiopharmaceuticals. To overcome this, Siemens PETNET Solutions employs standardized and validated equipment, dedicated and experienced scientists and pharmacists, and automated processes in combination with unique redundant back-up production. As such, the company is able to offer reliable access to Amyvid.
With a commitment to high quality and industry leadership, Siemens PETNET Solutions, a wholly owned subsidiary of Siemens Medical Solutions USA, Inc., has established a manufacturing and distribution agreement with Eli Lilly and Company, serving as the largest U.S. supplier of Amyvid. Siemens PETNET Solutions will begin supplying the radioactive diagnostic agent to imaging centers in limited U.S. markets beginning in June 2012. By the end of the year, the companyanticipates having 25 cGMP-certified manufacturing centers and co-located radiopharmacies commercially offering the compound.
Quantification and localization of Amyloid may enable accurate, more confident interpretation
Because some amyloid tracer is naturally retained in the normal brain, it is important to appropriately differentiate between white matter uptake and gray matter amyloid plaque deposits. While amyloid within the brain's white matter is, in most cases, considered normal, uptake in the gray matter may indicate abnormal activity.(8) Because gray and white matter are interlaced in such a compact way, distinguishing the two can be challenging. Once localized, accurately quantifying the presence of amyloid plaques may help to more confidently interpret an amyloid scan.(9) In cases where the intensity of amyloid uptake is insufficient, it may become challenging to accurately interpret based on visual assessment alone. Therefore, equally important to localization is quantification.(8,9)
Traditional scanners in use today often lack the fine volumetric resolution and high-contrast ratio required to precisely differentiate between gray and white matter. Inherent scanner drift as well as inaccurate attenuation correction impact the accuracy of acquired quantitative data. In addition, conventional interpretation software does not offer automatic quantification and leaves the reader to rely solely on subjective interpretation.
With the new Biograph mCT from Siemens, physicians can attain the highest image quality(10) and quantifiable results that are accurate. With its OptisoHD Detection System, UltraHD-PET and acquisition matrix of 400 x 400, Biograph mCT enables physicians to visualize different brain matter with the industry's finest volumetric resolution(11) of 87mm(3) and four times improvement in contrast (signal to noise). With its unique combination of daily calibration and precise anatomical and functional co-registration, Biograph mCT can make a quantifiable improvement in diagnostic confidence in dementia diagnosis.
syngo.PET Amyloid Plaque, Siemens' proprietary quantification software, is intended to take a patient's PET amyloid exam and automatically register it against a reference model of a PET amyloid brain. Siemens' proprietary affine registration algorithm has been shown in research(12) to have a correlation coefficient of 0.98 to the Fleisher method.(8) Pioneered by Dr. Adam Fleisher, this reference model identifies six optimal zones to evaluate pathological levels of amyloid plaque burden. syngo.PET Amyloid Plaque enables physicians to calculate uptake ratios. Uptake ratios, such as SUVr, can be compared to Fleisher thresholds, thus allowing to reflect pathological levels of amyloid.(8) Combined with visual assessment, these capabilities may give physicians added confidence in determining amyloid plaque burden -- for instance, in borderline cases, which otherwise could result in inconclusive or false scanning reports.(9)
Support for establishing new imaging services
Siemens has a recognized portfolio of programs to help customers establish and grow their PET imaging offerings and provide new services to their communities. Siemens imaging outreach program includes a broad range of exclusive offerings, including business plan development, site readiness consulting, optimized scanner protocols, workflow consulting, training and marketing support.
The impact of Alzheimer's disease
With aging populations and extended life expectancies, the number of Alzheimer's cases in the United States and worldwide is growing at epidemic levels. Progressing steadily and unmercifully, Alzheimer's disease is now the sixth leading cause of death in the United States. With 5.4 million Americans living with the disease -- and another person joining that group every 69 seconds -- this number is predicted to triple by 2050.(3) As deaths from stroke, cancer and heart disease decreased significantly between 2000 and 2008, Alzheimer's-related deaths rose 66%.(3) It is estimated that one in five patients diagnosed with probable Alzheimer's disease do not end up having Alzheimer's disease pathology upon autopsy.(13,14)
Indication and Important Safety Information About Amyvid
Indications and Usage
Amyvid is indicated for Positron Emission Tomography (PET) imaging of the brain to estimate beta-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's Disease (AD) and other causes of cognitive decline.
A negative Amyvid scan indicates sparse to no neuritic plaques and is inconsistent with a neuropathological diagnosis of AD at the time of image acquisition; a negative scan result reduces the likelihood that a patient's cognitive impairment is due to AD. A positive Amyvid scan indicates moderate to frequent amyloid neuritic plaques; neuropathological examination has shown this amount of amyloid neuritic plaque is present in patients with AD, but may also be present in patients with other types of neurologic conditions as well as older people with normal cognition. Amyvid is an adjunct to other diagnostic evaluations.( )
Limitations of Use:
A positive Amyvid scan does not establish a diagnosis of AD or other cognitive disorder. Additionally, the safety and effectiveness of Amyvid have not been established for predicting development of dementia or other neurologic condition or monitoring responses to therapies.(1)
Amyvid is supplied in 10 mL, 30 mL, or 50 mL multidose vials containing 500-1900 MBq/mL Florbetapir F 18.
Important Safety Information
WARNINGS AND PRECAUTIONS
Risk for Image Misinterpretation and Other Errors
Errors may occur in the Amyvid estimation of brain neuritic plaque density during image interpretation.
Image interpretation should be performed independently of the patient's clinical information. The use of clinical information in the interpretation of Amyvid images has not been evaluated and may lead to errors. Other errors may be due to extensive brain atrophy that limits the ability to distinguish gray and white matter on the Amyvid scan as well as motion artifacts that distort the image.
Amyvid scan results are indicative of the brain neuritic amyloid plaque content only at the time of image acquisition and a negative scan result does not preclude the development of brain amyloid in the future.
Amyvid, similar to other radiopharmaceuticals, contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer. Ensure safe handling to protect patients and health care workers from unintentional radiation exposure.
MOST COMMON ADVERSE REACTIONS
The most common adverse reactions reported in clinical trials were headache (1.8 percent), musculoskeletal pain (0.8 percent), fatigue (0.6 percent), nausea (0.6 percent), anxiety (0.4 percent), back pain (0.4 percent), blood pressure increased (0.4 percent), claustrophobia (0.4 percent), feeling cold (0.4 percent), insomnia (0.4 percent), and neck pain (0.4 percent).
Pharmacodynamic drug-drug interaction studies have not been performed in patients to establish the extent, if any, to which concomitant medications may alter Amyvid image results.
For Full Prescribing Information, visit http://pi.lilly.com/us/amyvid-uspi.pdf.
AM HCP ISI 06APR2012
About Agenda 2013
Launched recently by Siemens Healthcare Sector, Agenda 2013 is a two-year global initiative to further strengthen the Healthcare Sector's innovative power and competitiveness. Specific measures will be implemented in four fields of action: Innovation, Competitiveness, Regional Footprint and People Development.
About Siemens Healthcare
The Siemens Healthcare Sector is one of the world's largest suppliers to the healthcare industry and a trendsetter in medical imaging, laboratory diagnostics, medical information technology and hearing aids. Siemens offers its customers products and solutions for the entire range of patient care from a single source - from prevention and early detection to diagnosis, and on to treatment and aftercare. By optimizing clinical workflows for the most common diseases, Siemens also makes healthcare faster, better and more cost-effective. Siemens Healthcare employs some 51,000 employees worldwide and operates around the world. In fiscal year 2011 (to September 30), the Sector posted revenue of 12.5 billion euros and profit of around 1.3 billion euros. For further information please visit: www.siemens.com/healthcare.
Amyvid(TM) is a trademark of Eli Lilly and Company. AM77835
(1) Hyman BT, Phelps CH, Beach TG, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's Disease. Alzheimers Dement. 2012;8:1-13.
(2) Mirra SS, Heyman A, McKeel D, et al; and participating CERAD neuropathologists. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD): part II: standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991;41(4):479-486.
(3) Thies W, Bleiler L; Alzheimer's Association. Alzheimer's Association report: 2012 Alzheimer's disease facts and figures. Alzheimers Dement. 2012;8:131-168.
(4) The syngo.PET Amyloid Plaque neurology software is pending 510(k) clearance, and is not yet commercially available.
(5) Amyvid [package insert]. Indianapolis, IN: Eli Lilly and Company; 2012.
(6) McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's Disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's Disease. Alzheimers Dement. 2011;7:263-269.
(7) Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer's Disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's Disease. Alzheimers Dement. 2011;7(3):280-292.
(8) Adam S. Fleisher et al: "Using Positron Emission Tomography and Florbetapir F 18 to Image Cortical Amyloid in Patients With Mild Cognitive Impairment or Dementia Due to Alzheimer Disease", Archives of Neurology, July 12, 2011
(9) Camus et al EJNMMI (2012) 39:621-631; Using PET with 18F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment; Qualitative visual assessment of the PET scansshowed a sensitivity of 84.6%; however, the quantitative assessment of the global cortex SUVr showed a sensitivity of 92.3%.
(10) 2011 PET Image Quality Survey conducted in the U.S. and Europe as a custom study by IMV, a neutral third party market research company.
(11) Based on Competitive literature available at time of publications. Data on file.
(12)J.-M. Peyrat, A. Joshi, M. Mintun, J. Declerck: "An automatic method for the quantification of uptake with Florbetapir imaging", SNM Publication No.: 210, Reference #: 1311229, http://www.snm.org/index.cfm?PageID=11533
(13) Lim A, Tsuang D, Kukull W, et al. Clinico-neuropathological correlation of Alzheimer's disease in a community-based case series. J Am Geriatr Soc. 1999;47(5):564-569.
(14) Petrovitch H, White LR, Ross GW, et al. Accuracy of clinical criteria for AD in the Honolulu-Asia Aging Study, a population-based study. Neurology. 2001;57(2):226-234
SOURCE Siemens Healthcare