The focus, in this instance, is not a therapeutic intervention, but rather a test using a radioactive imaging agent– a dye, brand name, Amyvid (florbetapir)–which is to be used in brain PET scans to identify amyloid clumps. The presence of amyloid in the brains of Alzheimer’s patients has been observed post mortem in autopsies. However, amyloid plaques have also been found in the brains of at least 20% of healthy elder adults with no cognitive problems. Thus, the finding of amyloids doesn’t mean the person has Alzheimer’s.
Furthermore, FDA acknowledges that most doctors are not trained to interpret brain scan results–raising further doubts about the justification for its marketing approval of Amyvid. The test will likely result in a high percentage of false-positives greatly expanding the number of people mistakenly identified as having Alzheimer’s. Such a flawed test is of no clinical value–it will increase anxiety, add confusion for seniors and their families, and it will increase healthcare costs without any benefit for patients with Alzheimer’s.
As a thoughtful comment on Forbes website points out, "(sadly) amyloid imaging does nothing to contribute in any substantive way to a change in standard or attempted management of dementia."
The dye was developed at the University of Pennsylvania which reaped a hefty profit when Eli Lilly bought it for $800 million. News of FDA’s approval–a move, which Forbes reported, "took most people who watch pharmaceutical companies by surprise"– was accompanied by flim flam hype in an effort to overcome its negative aspects by claiming those aspects to be positives.: "We’re excited. The approval means that this product will finally be available to the patients who need, and can benefit from, this," said Avid Radiopharmaceuticals’ founder and chief executive officer, Daniel Skovronsky, 39, a Penn neuropathologist.
In point of fact, Lilly nadmits in the drug’s label that: “A positive Amyvid scan does not establish a diagnosis of AD or other cognitive disorder.”
To overcome the lack of professional competence to read PET scans, the FDA worked with Eli Lilly to develop a three-hour online crash training program for doctors!!
However, the professional incompetence problem is hardly resolved.
Forbes reports that Lilly’s Amyvid prescribing label discloses that in a 59-patient study in which ALL Amyvid readers of a patient’s Alzheimer’s status–that was later determined by autopsy–got at least 5% and up to 14% of diagnoses wrong. This inconsistency indicates that the test is inaccurate, not objective, is dependent on subjective interpretation.
Though it lacks a clinical justification for its use, Amyvid has a commercial use for drug developers.
Shirley Wang of The Wall Street Journal notes that those who favor using Amyvid and similar agents currently under development have said that such technology will accelerate research by helping to identify people at high risk of developing Alzheimer’s and to enroll such people in clinical drug trials. Matthew Herper of Forbes states: "Where tests like Amyvid will obviously be very useful is in testing new drugs. If drug companies can screen out patients who are likely not to have Alzheimer’s, they are far more likely to be able to show that medicines aimed at Alzheimer’s are effective in clinical trials…. This really is a clever move by Lilly to make some profit on a research tool. "
What an ingenious utilitarian use for a flawed, inaccurate screening test! Eli Lilly will be marketing a test–with FDA’s seal of approval–that will stigmatize and traumatize hundreds of thousands of elder people who will then be corralled to serve as free human drug testing subjects!
Eli Lilly has been enormously successful in marketing clinically useless drugs with debilitating side-effects that became blockbuster sellers, thanks to aggressive, unethical marketing tactics –Oraflex, Evista, Prozac, Zyprexa, Xigris, to name a few.
In 2001, having gained FDA approval of Xigris for the treatment of sepsis, which it sold for $6,800, then raised to $8,000 per 4-day course of treatment,
Eli Lilly’s chairman, president and CEO, Sidney Taurel, told shareholders: "No medicine better symbolizes our mission than Xigris," calling it "one of our industry’s genuine breakthroughs."
But Xigris was found to be worthless for the treatment of sepsis shock–it failed to show a survival benefit. To promote the use of Xigris, Lilly embarked on a deceptive marketing campaign to overcome negative evidence–i.e. increased bleeding and deaths in clinical trials. Lilly’s aggressive marketing blitz included manipulating–with cash payments–a task force of 20 scientists and hospital directors charged with formulating sepsis clinical guidelines. The guidelines recommended Xigris despite negative evidence from clinical trials. The company ultimately withdrew Xigris in 2011 after cashing in about $1 Billion.
If the FDA’s goal in its licensing determinations is to bankrupt the nation’s healthcare budget by approving worthless, all-too-often hazardous drugs, vaccines, and drug devices that undermine rather than improve health, it is doing a commendable job!
Vera Sharav
THE WALL STREET JOURNAL
Alzheimer Diagnosis Possible With Scan
By SHIRLEY S. WANG
A much-anticipated test developed by Eli Lilly & Co. that detects the presence of proteins in the brain that are related to Alzheimer’s disease was approved Friday by the Food and Drug Administration.
The tool could enable clinicians to detect Alzheimer’s earlier and more accurately in patients at the earliest sign of memory problems—a potential boon to treatment and developing drugs against the disease.
The test uses a chemical called florbetapir, known by the brand name Amyvid, which is a radioactive agent that tags clumps of a sticky substance called an amyloid. Amyloid proteins are hallmarks of Alzheimer’s disease. The chemical, which costs $1,600 per dose, then is detected using a brain imaging technique called positron emission tomography, known as PET scans.
For patients who already have some symptoms of cognitive decline, a positive scan suggests that moderate to frequent amyloid plaques are present in the brain, which is consistent with Alzheimer’s disease.
If the scan is negative, indicating no clumps or few clumps of amyloid, "that gives the clinician a clue that Alzheimer’s is less likely to be the cause of those symptoms," said Daniel Skovronsky, who developed the agent and is the global brand-development leader for Amyvid at Lilly. For those patients, doctors can then look for other potential causes of the memory decline, which may have another prognosis or be treated differentially than Alzheimer’s, he said.
The imaging agent can’t be used to diagnose someone with Alzheimer’s disease if the individual doesn’t experience memory impairment because the presence of amyloid in the brain doesn’t alone suggest that someone has Alzheimer’s.
Before the development of imaging agents, amyloid plaques could be determined only after death, by examining the brain during an autopsy.
Some 20% of cognitively healthy older adults have been found during autopsies to have large quantities of amyloid in the brain, according to Denise Park, director of the Center for Vital Longevity at the University of Texas at Dallas.
"It is likely to play an important role in learning both how to diagnose and treat the disease, but it’s still an open question at this point for asymptomatic people," said Dr. Park, a behavioral and brain-sciences professor who uses Amyvid in her research on aging of healthy older adults.
Amyvid will be available in limited quantities starting in June, Lilly said.
New techniques, including advances in brain scans, are helping to reveal the hidden anatomy of brain wiring and giving scientists a new understanding of how thoughts, memories and emotions are formed. WSJ’s Robert Lee Hotz reports.
A lack of ability to reliably diagnose patients in the early stages of the Alzheimer’s disease has hampered research. Some experts believe that investigational drug trials have failed because patients enrolled in such studies already had progressed too far for the treatments to be effective.
Proponents of using florbetapir and similar agents that are being developed have said that such technology will accelerate research by helping to accurately identify people at high risk of developing the condition and to enroll such people in therapeutic trials.
It also may be useful in tracking disease progression in the brain.
Some experts have questioned how useful the test is since no treatments are available that significantly alter the course of the disease. But some doctors believe that patients may find a diagnosis helpful for planning purposes or just to know for certain that they have Alzheimer’s.
Another concern expressed by the FDA is whether doctors can read the scan results accurately and consistently. The agency in March of last year declined to approve the compound and said the company needed to establish a program to train doctors to interpret accurately the scan results.
Lilly has worked with the FDA and experts to develop three-hour online and in-person training programs for physicians.
"There are a lot of patients who have been groping in the dark for some time now, and here’s an opportunity to shine a light in their brain and find out if there’s amyloid or not," Dr. Skovronsky said.
Write to Shirley S. Wang at shirley.wang@wsj.com
A version of this article appeared April 9, 2012, on page B1 in some U.S. editions of The Wall Street Journal, with the headline: Alzheimer Diagnosis Possible With Scan.
Copyright 2012 Dow Jones & Company, Inc. All Rights Reserved
~~~~~~~~~~~~FORBES
Why Eli Lilly’s Alzheimer’s Imaging Test Is No Breakthrough
by Matthew Herper
Sometimes (not always, certainly, but sometimes), Mr. Market is pretty smart.
Take the way shares of Eli Lilly are reacting to the news that the Food and Drug Administration, in a move that took most people who watch pharmaceutical companies by surprise, approved the company’s imaging agent for understanding and diagnosing Alzheimer’s disease. Lilly shares have fallen 1.3% along with the broader market. Not exactly what you’d expect if the drug, Amyvid (generic name: florbetapir) is going to be widely used to diagnose one of the most dreaded diseases in the world, as you might expect after reading this Wall Street Journal article.
The problem, straight from the drug’s label: “A positive Amyvid scan does not establish a diagnosis of AD or other cognitive disorder.”
The idea behind the drug is wonderful, and really could change the way Alzheimer’s is diagnosed and treated over the long-term. It’s an imaging agent that allows radiologists to see signs of the diseases on a Positron Emission Tomography (PET) scan, potentially allowing for earlier diagnosis. Right now, the test will be used mainly to rule out Alzheimer’s — patients who have no brain plaque don’t have Alzheimer’s. A positive result actually doesn’t mean the patient has Alzheimer’s.
It’s unlikely that the drug will be used as an important diagnostic in the near term. ISI Group pharmaceuticals analyst Mark Schoenebaum darted off a note to his clients over the weekend showing that right now, the potential sales for Amyvid will be less than $100 million a year. The reason: right now, the Centers for Medicare and Medicaid Services (CMS) won’t pay for the drug. Lilly told Schoenebaum that it is working with CMS to “new path forward for PET coverage.”
What if CMS does decide to pay? Schoenebaum estimates that even then, it’s not a huge opportunity. There are 450,000 new Alzheimer’s disease cases every year, he writes. The wholesale acquisition cost of Amyvid is $1600. Assuming the drug is sold at a 10% discount, that means that the potential U.S. market is $650 million. But General Electric, Bayer, and other companies are developing rival products.
Amyvid was rejected last year because the FDA thought Lilly needed a better training program in place to make sure different doctors come to similar conclusions when they read the scans. Because the resulting program looks burdensome, Schoenebaum thinks that Amyvid only gets a third of this new market, making total U.S. sales $200 million. Another $300 million in sales are possible in Europe if the drug is approved there. Even in the best-case scenario, this isn’t a huge product, financially.
But an even bigger concern, as former fund manager Nathan Sadeghi-Nejad said on Twitter, is how useful such a test would be clinically. In a 59-patient study in which a patient’s Alzheimer’s status was later determined by autopsy, all Amyvid readers got at least 5% and up to 14% of diagnoses wrong. Having multiple readers helps with this, but it still indicates that this is a subjective test.
Where tests like Amyvid will obviously be very useful is in testing new drugs. If drug companies can screen out patients who are likely not to have Alzheimer’s, they are far more likely to be able to show that medicines aimed at Alzheimer’s are effective in clinical trials. Having those non-Alzheimer’s patients in a study is going to wash out the efficacy of a new drug. And it’s possible that if a drug affects an Amyvid scan, that could be correlated with changes in memory. This really is a clever move by Lilly to make some profit on a research tool.
Someday these imaging tests — or better yet, blood tests that are in the early stages of development — may really help us detect Alzheimer’s before symptoms occur. That will dramatically increase our chances of treating it. But the approval of this test is only a step in that direction.