The new radioactive imaging agent has been bought from its developer, Germany’s Bayer AG by Indian drugmaker Piramal Healthcare.
Now in late clinical trials and likely to be approved by federal drug regulators late this year, florbetaben — an experimental radioactive agent — is expected to help doctors make an early diagnosis of Alzheimer’s disease in people suffering the serious memory and cognitive problems of dementia.
That’s good news for millions of people worldwide who are at risk of developing the feared mind-robbing disease. An early way to detect the disease will help scientists find a cure for Alzheimer’s, which has been elusive so far. Medical experts believe that the drugs being investigated in clinical trials to treat this neurodegenerative disease have failed mainly because the patients enrolled in such trials are suffering late-stage Alzheimer’s that’s progressed too far for the drugs to be effective.
The most common cause of dementia, Alzheimer’s is often called a mind-robbing disease because those who have it eventually lose their memory, their cognitive skills, and even the capacity to feed themselves. A progressive disease that mostly affects people over 60 years old, it can lead to premature death.
More than 26 million people worldwide were suffering from Alzheimer’s in 2006, and health experts estimate that this number could reach more than 100 million by 2020.
In the United States, about 5.4 million people are living with Alzheimer’s disease, and there are 15.2 million caregivers of people with Alzheimer’s and other dementias, according to the Alzheimer’s Association.
But there’s no drug so far that can stop the march of this dreaded disease — treatments are meant to alleviate symptoms and, combined with the services and support, improve the quality of life for millions of sufferers.
Experts say the search for a cure has been hampered the inability to diagnose Alzheimer’s patients reliably in the early stages of the disease. So now that florbetaben — and other similar radioactive agents — have been developed, clinicians will have a tool to detect Alzheimer’s accurately at the earliest sign of memory problems.
Like a similar agent from Lily & Co. named Amyvid — which was approved in mid April by the U.S. Food and Drug Administration — florbetaben is a new radioactive agent that tags the amyloid plaque that builds up in the brains of people with Alzheimer’s disease.
The buildup of amyloid, a sticky protein, is one of the hallmarks of Alzheimer’s and radioactive imaging agents like florbetaben tags clumps of this protein.
Dr. Marwan Sabbagh, of Banner Sun Health Research Institute in Sun City, Arizona explains that florbetaben is injected into the brain of a patient, who is then made to undergo a brain imaging scan called positron emission tomography (PET). Under a PET, and with florbetaben, the plaques light, he explains.
Dr. Sabbagh and colleagues conducted a late-stage testing comparing PET scans using florbetaben on brain tissue from 31 people in the months before they died to tissue taken after death, at autopsy. Currently, the presence of amyloid plaque at autopsy is the only way to confirm a diagnosis of Alzheimer’s. Their study was funded by maker Bayer Healthcare Berlin, which plans to submit the results with an application for FDA approval.
The scans correctly identified 100 percent of people who had plaque at autopsy. But WebMD reports a small dent in the test’s accuracy: one person who tested positive for plaque didn’t end up having any.
The findings are scheduled to be presented at the annual meeting of the American Academy of Neurology in New Orleans, Louisiana, to held on April 21-28. Since they have not undergone the peer review in which outside experts scrutinize the data prior to their publication in a medical journal, the findings are considered preliminary.
Improving the life quality of Alzheimer’s patients
Some doctors argue that it’s pointless to have a radioactive agent that will help diagnose Alzheimer’s when there’s still no drug to cure the disease. But Dr. Sabbagh argues that early diagnosis allows patients to take medications and undergo other interventions that can keep dementia at bay for longer.
More importantly, Dr. Sabbagh notes that medications that can actually slow the progression of the disease are now in late-stage testing. Once these drugs become available, the tests could help doctors select patients for early treatment — and this can really spell the difference for people with Alzheimer’s.
A diagnosis can also help families create plans to help patients, notes Dr. Rachelle S. Doody, director of the Alzheimer’s Disease and Memory Disorders Center at the Baylor College of Medicine in Houston, Texas.
Radioactive agents have limits
But the new radioactive imaging agents can’t pinpoint people with Alzheimer’s. This is because the scans detect amyloid plaque in the brain — but not Alzheimer’s itself. People with Alzheimer’s always have amyloid plaque — but having the plaque does not mean a person has Alzheimer’s. This is why the imaging tests shouldn’t be performed on people who don’t have symptoms of Alzheimer’s and memory problems, Dr. Doody explains.
“A diagnosis of Alzheimer’s requires lots of bits of information. This is not a revolution for the diagnosis of Alzheimer’s but one of those bits of information that can be helpful,” says Dr. Doody, who was not involved with the work.
But the florbetaben and similar agents can provide skilled doctors a vital piece of information that can be used to diagnose Alzheimer’s — or rule it out, experts say.
For people with memory problems, disorientation, and other symptoms of Alzheimer’s, a positive scan would mean there’s a “high probability of Alzheimer’s or that Alzheimer’s is contributing to the patient’s (memory problems),” Dr. Sabbagh tells WebMD. A negative scan in a person with symptoms would mean the probability of Alzheimer’s is extremely low, he explains.
What’s more, the tests should only be performed by a skilled doctor with experience in diagnosing Alzheimer’s, Dr. Doody warns, because the scan results need to be read accurately and consistently. But like the makers of similar agents, Bayer will likely develop a program to train doctors to interpret the results for its drug.
Better than its cousins?
Right now, no one knows for sure which radioactive agent works best, since florbetaben and similar agents haven’t been compared in a head-to-head study.
But Dr. Sabbagh argues that one advantage of florbetaben is that it appears to last relatively long before it loses its radioactivity. That means — unlike the imaging agents that can only be used at the institution where they are made — florbetaben can be shipped and used at centers worldwide.
The most common side effects found in Dr. Sabbagh’s study –which were also found to be short-lived — were discomfort and bruising in the area where the drug is injected, headache and flushing.
Bought by Indian drug maker
On April 16, Indian drugmaker Piramal Healthcare bought the rights for florbetaben from Germany’s Bayer AG, seeing revenue potential of US$1.5 billion from this new imaging agent.
“There are about 25 million patients of Alzheimer’s disease globally and it would grow to 100 million by 2020 … hence the segment has a huge revenue potential and has lower competition,” Piramal Chairman Ajay Piramal told reporters. “Post U.S., we plan to file for approvals in Europe and Japan as well,” he also said.
The global market is currently estimated at anywhere from US$1 billion to US$5 billion, and florbetaben is competing head with similar Alzheimer’s imaging agents from global pharmaceutical companies such as Eli Lilly and Co, Pfizer Inc and General Electric Co. to dominate this market.
As part of the deal, Piramal will acquire intellectual property, worldwide development, marketing and distribution rights of florbetaben and other clinical and pre-clinical assets of Bayer’s molecular imaging business. The deal’s financial aspects were not available.
The Indian company — which currently makes over-the-counter drugs and manufactures pharmaceutical products on a contractual basis — is making the acquisition through a newly created unit, Piramal Imaging SA. It is also setting up a dedicated global commercial team for florbetaben.
The imaging agents are expensive. No cost has been established for florbetaben but Amyvid is estimated to cost US$1,600 a dose. The PET scan that is used with the test can cost between US$3,000 and US$6,000. Worse, Medicare and most other insurers aren’t expected to immediately cover the imaging expense, when these agents become available in the U.S. market this year.