January 17, 2011 — GE Healthcare has announced Food and Drug Administration (FDA) approval of ioflupane iodine-123 injection (DaTscan), a contrast agent for use with single-photon emission computed tomography (SPECT) for detecting dopamine transporters (DaT) in suspected parkinsonian syndromes.
The agent is indicated for striatal DaT visualization to help differentiate essential tremor from tremor due to parkinsonian syndromes, including idiopathic Parkinson's disease, multiple-system atrophy, and progressive supranuclear palsy, as an adjunct to other diagnostic modalities.
With use of the new agent, SPECT scans show abnormal distribution of DaT in parkinsonian syndromes but are normal in other conditions, such as essential tremor and Alzheimer's disease. In August 2009, the FDA's Peripheral and Central Nervous System Drugs Advisory Committee voted 11 to 2, with 1 abstention, in favor of the agent providing a favorable risk/benefit ratio and being a useful adjunctive diagnostic tool.
The FDA granted the agent priority review because of "an unmet clinical need for an imaging agent to assist physicians in managing patients according to their dopaminergic status," notes a statement from GE Healthcare released January 14.
New Diagnostic Adjunct
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| Normal (left) and abnormal (right) DaTscan results. |
Currently, movement disorders are diagnosed with clinical and laboratory tests as well as neuropsychological evaluations, "which are not conclusive and may lead to misdiagnosis," Mark Stacy, MD, neurologist and director of the Duke Movement Disorders Clinic at Duke University Medical Center in Durham, North Carolina, comments in the company statement. "A new diagnostic adjunct to existing clinical assessments represents a meaningful contribution to the movement disorders field."
Approval of the agent was based on 2 phase 3 trials that confirmed the efficacy of the agent for visualization of DaT in the striatum, the company notes. "These studies, evaluating 284 adult patients with tremor, demonstrated the consistent performance of DaTscan in the visual detection of DaT distribution in the brain when compared with a reference clinical diagnosis."
The agent has been available in Europe since 2000 and has been used in nearly 300,000 patients in 32 countries, the company points out. It is classified as a schedule II controlled substance, accepted for medical use in the United States (with or without severe restrictions), and has a high potential for abuse that may lead to severe psychological or physical dependence as determined by the Controlled Substances Act, the company notes.
FDA Advisory Panel
During the FDA advisory panel meeting, reported by Medscape Medical News in August 2010, panelists were mainly positive about the product.
"This might make a real difference in 5% of patients seen by movement disorders specialists and 15% of patients seen by general practitioners, and that's an important number of patients," committee member Nathan Fountain, MD, associate professor of neurology at the University of Virginia, Charlottesville, told Medscape at that time. Dr. Fountain voted in favor of the agent.
"There are many circumstances I can think of and imagine where this could be a benefit, and the risks are very low," said Karl Kierburtz, MD, MPH, committee member and professor of neurology and community and preventive medicine at the University of Rochester, New York.
Dr. Kierburtz noted that in many instances DaTscan could help improve the diagnostic accuracy by clinicians and decrease some of the problems associated with other means of differential diagnosis — such as medication challenges, which often work poorly in the elderly or patients with dementia.
However, although the committee members pointed out the benefits of the agent, they also voiced concerns about how it might be used. "I have reservations about how widely and in what clinical situations it might be used," said committee member Peter Herscovitch, MD, from the National Institutes of Health Clinical Center, Bethesda, Maryland. "I'd be concerned that if it was widely available, it could be used if there is even a suspicion of a movement disorder."
Committee members emphasized that DaTscan was not suitable for screening or prognosis on its own. "We don't want to make this the gold standard for diagnosing Parkinson's disease. This should not be the comparator," added Gregory Holmes, MD, professor of medicine at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, who also voted in favor of the agent.
Efficacy and Safety Concerns
Those who voted against the agent did so because of safety concerns and doubts that GE Healthcare had proven the drug's clinical utility. Wilson DeCamp, PhD, the patient representative on the committee, voiced concerns that there had been 5 deaths in 8 completed clinical studies on the drug.
Company representatives responded that the deaths were unrelated to the agent, but Dr. DeCamp pointed out that DaTscan had been used in over 200,000 patients since it was approved for marketing in Europe in 2000 at that time, and "the risk to patients may have been underestimated," he said.
Stacy Rudnicki, MD, who also voted against the agent, voiced concerns that it had not been proven to be an aid in clinical management of patients with Parkinson's disease or dementia. She also noted that the question of whether DaTscan could influence outcomes was largely unanswered. Dr. Rudnicki is professor of neurology at the University of Arkansas, Little Rock.
In a presentation before the committee, Joel Perlmutter, MD, professor of neurology at Washington University School of Medicine, St. Louis, Missouri, said that after reviewing the scientific literature, he did not think that DaTscan was cost-effective.
He highlighted the difference in cost between DaTscan ($1500 per scan) and a month's trial of carbidopa or levodopa for a patient with possible PD ($150). "I don't think the data is sufficiently compelling, and the cost/benefit is marginal," he said. "It wouldn't change how I would treat a patient."
The agent is contraindicated for patients with known sensitivity to the active substance, any of the excipients, or iodine, the GE Healthcare statement notes. Warnings and precautions include hypersensitivity reactions (generally skin erythema and pruritus) or thyroid accumulation.
The injection may contain up to 6% free iodide (iodine 123 or I-123), the release notes. "To decrease thyroid accumulation of I-123, block the thyroid gland at least 1 hour before administration of DaTscan; failure to do so may increase the long term risk for thyroid neoplasia," the statement says.
In clinical trials, adverse reactions such as headache, nausea, vertigo, dry mouth, and mild to moderate dizziness were reported, the company notes. In postmarketing experience, hypersensitivity reaction and injection site pain have been reported.
Dr. Stacy has served as a consultant for GE Healthcare in the development of DaTscan. He has also received support through Duke University for the study of this agent.
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Cite this: FDA Approves DaTscan for Imaging of Dopamine Transporters - Medscape - Jan 18, 2011.
