reported mixed results from a midstage test of bapineuzumab in patients with Alzheimer's disease Tuesday.
Overall, bapineuzumab conferred no statistically significant benefit on the 240 patients enrolled in the phase II study. However, the drug was at least partially effective in a subgroup of patients lacking a higher genetic risk for developing Alzheimer's, the companies said Tuesday.
Based on these overall results, Elan and Wyeth said the ongoing phase III clinical trials of bapineuzumab will continue, although the companies did not say whether changes would be made to these studies.
Elan shares closed Monday at $27.11. Wyeth shares closed at $43.08.
Given the high stakes surrounding bapineuzumab, Tuesday's results from the phase II study are easily the most
highly anticipated biotech event
of the year. Elan and Wyeth are developing bapineuzumab to be the first Alzheimer's drug to modify the course of the disease and not just treat its symptoms.
Such a drug, if approved, might be the biggest ever sold, with sales potentially reaching $10 billion or more.
It remains to be seen whether bapineuzumab can be that mega-blockbuster Alzheimer's drug. The case laid out by Elan and Wyeth Tuesday morning has something for bulls and bears to feast on. The companies held back much of the data from the phase II study so that it can be presented at a meeting of Alzheimer's researchers in late July.
In Tuesday's announcement, Elan and Wyeth chose not to say much at all about the overall treatment effect of bapineuzumab compared to placebo on the entire group of patients with mild to moderate Alzheimer's enrolled in the study, which was the prospectively defined goal of the study. Instead, the companies broke down the results based on two retrospectively defined subgroups -- patients with and without a gene called ApoE4.
Patients who are non-carriers of the ApoE4 gene are not at an increased risk for developing Alzheimer's. These "non-carriers" make up between 40% and 70% of the overall population.
In these non-carrier patients, treatment with bapineuzumab compared to placebo resulted in a statistically significant benefit in two measures of cognitive function -- the so-called ADAS-cog test and the Neuropsychological Test Battery, or NTB.
Furthermore, non APoE4 patients reported a statistically significant result compared to placebo on one of two measures of functional benefit -- the Clinical Dementia Rating -- Sum of Boxes (CDR-SB). However, this was only a tertiary functional endpoint of the study. On the prespecified cognitive primary endpoint, the Disability Assessment Scale of Dementia (DAD), there was only a trend in favor of bapineuzumab.
These patients also had less loss of brain volume after treatment with bapineuzumab compared to similar patients treated with placebo.
Elan and Wyeth did not provide any information regarding the numerical magnitude of the functional or cognitive benefit resulting from bapineuzumab treatment, nor did the companies disclose which of the three doses of drug used in the study was the most effective.
Patients who carry the ApoE4 gene have a higher risk for developing Alzheimer's. In these "carrier patients," however, bapineuzumab was ineffective on all cognitive and functional endpoints.
On the safety side of the study, there was a higher rate of brain swelling, or vasogenic edema, reported in ApoE4 carriers treated with bapineuzumab compared to placebo.
Elan and Wyeth began phase III studies of bapineuzumab late last year. Two studies are testing multiple doses of the drug in patients who do not carry the ApoE4 gene, while another two studies are testing a single dose of the drug in patients with the ApoE4 gene. Results are not expected for another two years.
There has been some hope amongst Elan and Wyeth supporters, fueled by talk from the companies themselves, that these phase II data would be strong enough to support approval of the drug. Tuesday, the companies made no mention of that accelerated approval strategy.
One of the leading theories for Alzheimer's says that sticky plaques, or clumps of protein, called beta amyloid attach to nerve cells in the brain. These beta amyloid plaques are toxic and gradually break down the nerve cells, causing the loss of cognition and function that are the hallmarks of Alzheimer's.
Bapineuzumab is an antibody that is injected into a patient. Once there, the drug is supposed to seek out and attach itself to these beta amyloid plaques; doing so allows the body's immune system to clear them from the brain.
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