The companies said they would discontinue all other studies of the drug bapineuzumab in its intravenous (IV) form, including two more late stage trials and follow-up extension studies, in patients with mild to moderate Alzheimer's.

The result marked the second such failure announced in recent weeks and was especially disappointing as bapineuzumab had been given a better chance of success in the patients studied in the second trial.

Attention will now turn to solanezumab, a similar drug being developed by Eli Lilly & Co that is also considered a long-shot to succeed, but will still carry fading hopes at least until some late stage results on that medicine are released later this year.

Shares in Pfizer, J&J and Lilly all fell in after-hours trading following news of the latest disappointment.

Industry analysts have said that many investors were holding Pfizer and Lilly shares as an insurance policy in case the Alzheimer's drugs were to succeed. Any successful Alzheimer's treatment is likely to reap many billions of dollars in sales.

Analysts had annual sales forecasts for bapineuzumab ranging from zero to more than $1 billion. ISI Group analyst Mark Schoenebaum, in a research note, said the scrapping of the drug would lower his Pfizer share price estimate by about $1.

J&J said it would take a charge of $300 million to $400 million in the third quarter related to discontinuation of the bapineuzumab Phase III clinical trial program.

Bapineuzumab failed to improve cognitive or functional performance compared with placebo in patients who did not carry a variation of a gene called ApoE4, according to initial results of the Phase III study released on Monday.

Pfizer on July 23 announced the failure in the first of four high-stakes trials, in patients with the ApoE4 gene variation. That trial was considered more of a long-shot based on poor results in earlier trials, but hopes were high that the data would prove more encouraging in ApoE4 non-carriers.

"We are obviously very disappointed in the outcomes of this trial. We are also saddened by the lost opportunity to provide a meaningful advance for patients afflicted with mild-to-moderate Alzheimer's disease and their caregivers," Steven Romano, head of Pfizer's Medicines Development Group, said in a statement.

EARLIER STAGE TREATMENT SEEN AS CRITICAL

While the bapineuzumab IV program is dead, the companies said a Phase II study of a subcutaneous formulation of the drug would continue. There were no plans at this time to study bapineuzumab in asymptomatic patients or those with an earlier stage form of the disease, a spokeswomen for Pfizer and J&J said.

Many scientists and researchers believe any treatment to be successful must be used at a very early stage of the disease or even before it occurs in high risk patients. Many had predicted the late stage studies of bapineuzumab would fail because they were treating patients whose brains were already damaged.

Dr. Sam Gandy of the Alzheimer's Disease Research Center at Mount Sinai School of Medicine in New York said in an email he "would have loved to have been pleasantly surprised and wrong," but he is neither.

William Thies, chief scientific officer of the Alzheimer's Association, said despite the trial failures he was anxious to see a full analysis of the results.

"These studies are terribly important for us to learn about Alzheimer's disease, and that part of the process is just starting as the data continues to be crunched in a variety of ways," Thies said.

He said the results in mild to moderate patients would not necessarily exclude bapineuzumab from prevention trials, such as the Dominately Inherited Alzheimer's Network (DIAN) - a consortium that enrolls people who are genetically predisposed to develop the disease at an early age. The drugs to be used in that study are expected to be announced by year's end.

"One of the strong thoughts in the field is that you really have to treat people before they become demented," said Thies, noting that is the point of the DIAN study. "Out of hand this does not automatically exclude bapineuzumab from that study."

Bapineuzumab IV is an injectable monoclonal antibody that works by attacking a protein called beta-amyloid that is believed by many researchers to be a leading cause of Alzheimer's disease.

Morningstar analyst Damien Conover said most investors did not expect bapineuzumab to succeed, but were hoping for a home run because of the large unmet need for such a treatment.

Alzheimer's is the most common form of dementia and the sixth leading cause of death in the United States. An estimated 5 million Americans are believed to have the disease. An estimated 36 million people worldwide are believed to have dementia, including Alzheimer's disease.

"The probability of success in these trials was very low in the minds of most investors," said Anthony Butler, an analyst with Barclays Capital. "The overall impact financially is negligible. But it's a sentimental negative, for sure, and I think that's critical."

He said the news was likely to have a negative impact on Lilly as well since its drug works in a similar manner to bapineuzumab.

Pfizer shares fell 3 percent to $23.54, J&J shares slid 1.2 percent to $68, and Eli Lilly shares were down 2.2 percent to $42.75 in extended trading.

(Additional reporting by Susan Kelly and Julie Steenhuysen in Chicago and Anna Yukhananov in Washington; editing by Matthew Lewis and Richard Chang)

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