are using a new and unproven endpoint to measure the memory and mental status of patients in phase III trials of their experimental Alzheimer's drug bapineuzumab, say sources familiar with the studies' protocols.
By creating their own test to measure bapineuzumab's efficacy, Elan and Wyeth are seeking an alternative to the so-called ADAS-cog, despite that test's imprimatur as the gold standard measure of cognitive function. The ADAS-cog has been used as the basis for approval for all Alzheimer's disease drugs to date.
Elan has devised a new clinical endpoint, which it calls the Neuropsychological Test Battery, or NTB. The Irish drugmaker has used the NTB in previous studies of its Alzheimer's drugs to demonstrate improvements in the mental status of patients when similar measurements using ADAS-cog showed no benefit.
This is the first time, however, that Elan and partner Wyeth will attempt to convince regulatory authorities in the U.S. and Europe that the NTB should be considered as the basis to approve a new Alzheimer's drug.
The companies are pushing the test even though the NTB has not yet been independently validated by anyone outside the two companies, nor has it ever been used as a primary endpoint in any pivotal trial for Alzheimer's.
The ADAS-cog test, by comparison, is the most widely recognized and utilized measure of cognition in Alzheimer's drug trials.
All four Alzheimer's drugs currently on the market used the ADAS-cog test as the endpoint of their phase III trials. As well, the only other two drug companies with experimental Alzheimer's drugs in phase III studies right now --
(MYGN - Get Report)
(MDVN - Get Report)
-- are using the measure as their primary endpoint in their respective studies.
Dr. Peter Davies, an Alzheimer's researcher at New York's Albert Einstein College of Medicine, questions why any company would seek to develop an alternative cognitive test when the standard and well-understood ADAS-cog test has proven time and time again to be entirely adequate.
"What we need are better Alzheimer's disease drugs, not better tests," says Davies. "If a drug cannot show improvement in cognitive function using the ADAS-cog test, then the drug is not worth bothering with."
There is intense interest in bapineuzumab, both from the Alzheimer's research community and Wall Street, because it is the first antibody drug in Alzheimer's to reach phase III studies. Bapineuzumab is so closely tracked because it has been designed to actually improve a patient's memory and mental status instead of merely temporarily treating the symptoms of Alzheimer's.
Any drug that can modify or reverse the course of Alzheimer's will generate billions of dollars in sales. The potential for blockbuster profits from bapineuzumab has pushed Elan's stock price higher. Shares hit $26 earlier this month, a level they hadn't seen since 2005.
Elan and Wyeth have announced plans to conduct four bapineuzumab phase III trials, which will track approximately 4,000 patients with mild to moderate forms of Alzheimer's. Two of those studies began enrolling North American patients in December; the remaining two studies, to be conducted in Europe and the rest of the world, are expected to begin soon.
To date, neither Elan nor Wyeth has announced publicly the primary efficacy endpoints of these studies. The companies have stated only that the efficacy of bapineuzumab will be measured using one cognitive and one functional endpoint.
Two Alzheimer's researchers familiar with the study protocols for the bapineuzumab phase III studies have confirmed that NTB was chosen as the primary endpoint, with the ADAS-cog test listed as a secondary endpoint.