Keenly awaited details on Elan and Wyeth's new Alzheimer's drug bapineuzumab show it raised the risk of a potentially serious side effect, especially in people with a genetic risk of the disease, the companies said on Tuesday.
They said 12 people with mild-to-moderate Alzheimer's, who were treated with the drug, developed a build-up of fluid in the brain called vasogenic edema.
Ten of those cases were in people who have the ApoE4 gene, which significantly raises their risk of developing Alzheimer's disease. The other two were in non-carriers of the gene.
"Usually this occurred after the first or second dose," Dr Ronald Black, assistant vice president in neuroscience research at Wyeth, said in an interview. "About half of them had no symptoms at all, and about a third had minor symptoms."
Black said the side effect appeared to be "strongly related" to the dose of the drug people took. "The higher doses get more," he said.
None of those who received a placebo developed the brain-swelling condition. All those who suffered the side effect recovered from it, Black said.
The update on the antibody medicine, also known as AAB-001, has been closely watched by investors. If proven to work, the drug could be the first to modify the course of Alzheimer's disease, rather than just offering symptom relief.
Some analysts have forecast eventual annual sales of $13 billion.
Details of the study, presented at the Alzheimer's Association International Conference on Alzheimer's Disease in Chicago, help fill out the picture on the drug, which aims to fight deposits called beta amyloid plaques linked to the degenerative brain condition.
Genetic Differences
Preliminary findings released last month showed the drug failed to boost memory and functionality in most of 234 patients over 18 months.
Carriers of ApoE4, 60 percent of those who got the drug and 70 percent who got the placebo, did not show any improvement in their ability to think or function.
But in the non-carriers of ApoE4, the companies did find a statistically significant improvement in these measures.
"You can't conclude anything about the efficacy of the drug from this trial," said Dr Ronald Petersen of the Mayo Clinic in Rochester, Minnesota, who was briefed on the results.
"It's a secondary analysis. You have to go with what they pre-specified and what their endpoints were, and they didn't make those," said Petersen, incoming chairman of the Alzheimer's Association's scientific board and chairman of a safety monitoring board for a therapeutic vaccine Wyeth and Elan are working on for Alzheimer's.
The companies decided to conduct larger studies aimed at proving bapineuzumab worked in ApoE4 non-carriers, who make up about half of all Alzheimer's patients.
Black said the big difference in vasogenic edema between ApoE4 carriers and non-carriers prompted the companies to analyze the groups separately.
In the phase 3 study, the companies plan to give higher doses of the drug to people who do not carry the ApoE4 gene, and a single low dose to the ApoE4 carriers.
The companies plan to meet with regulators about the final design of the four late-stage clinical trials, which will involve 4,100 patients, Black said.