Alzheimer's drug from Pfizer, J&J may prove safer

Wed Jul 20, 2011 1:30am EDT

* Brain swelling problem may decrease over time

* Drug well tolerated in long-term study

* Some cases of mild vasogenic edema were undetected

* Studies may build confidence in once-battered drug

By Julie Steenhuysen

PARIS, July 20 (Reuters) - Experimental Alzheimer's drug bapineuzumab, from Pfizer (PFE.N) and Johnson & Johnson (JNJ.N), may be safer than originally thought, according to two studies by U.S. researchers released on Wednesday.

They said that a brain swelling condition called vasogenic edema, which caused a lot of worry over the drug's safety early on, may decrease over time.

"It looks like we can treat people for a number of years safely," Dr. Steven Salloway of Butler Hospital and Brown University in Providence, Rhode Island, told the Alzheimer's Association International Conference in Paris.

Salloway looked at the long-term safety of 194 patients in a mid-stage trial of the drug that stayed on treatment after the initial phase ended. Of those, 86 patients got the drug for at least 3 years and 43 were treated for at least 4 years.

About 24 percent of the patients had side effects possibly related to the drug, and some 85 percent of these were considered mild to moderate.

Cases of vasogenic edema, now called ARIA-E or Amyloid Related Imaging Abnormalities with Parenchymal Edema, appeared to lessen over time.

The risk of developing ARIA-E dropped from 6.7 percent in the first three infusions of the drug, to 2.7 percent for the fourth through the 10th treatment.

"That is very encouraging to me," Salloway said in an interview. "I think this is a transient condition."

"We've treated a lot of patients at at our center. I think it is very well tolerated," he said.

Larger, late-stage clinical trials will be needed to determine whether the drug works. Those studies are expected to stop enrolling patients in mid-2012.

There is no current treatment for Alzheimer's, which affects nearly 36 million people worldwide.

SWELLING WITHOUT SYMPTOMS

In a separate study of the drug, a team led by Dr. Reisa Sperling of Brigham and Women's Hospital and Harvard Medical School in Boston reviewed more than 2,000 MRI scans from 262 patients who participated in mid-stage studies of bapineuzumab.

She looked for cases of amyloid-related abnormalities on the scans that might represent vasogenic edema or tiny leaks in blood vessels.

The radiologists in the study were specifically looking for amyloid abnormalities in the brain that might have gone undetected because patients had no symptoms.

The team found 36 cases thought to be linked to treatment with bapineuzumab, including 15 new cases. None of these patients had symptoms of ARIA-E, which can include headache, memory loss, loss of coordination and disorientation.

Since these cases were not identified, many of these patients continued to be treated with bapineuzumab.

"They were treated through their ARIA and remained asymptomatic," Sperling said in an interview.

"For me that was reassuring. You see these changes in the MRI and they look a little frightening. The fact that they can potentially be treated and remain OK is reassuring."

The team also found that people treated with higher doses of bapineuzumab who have an Alzheimer's risk gene called APOE-4 tend to have more ARIA-E side effects, confirming the companies' decision to lower the dose of the drug in these patients.

Salloway said the mid-stage study he looked at was not meant to show whether the drug helped improve clinical symptoms, but the researchers were encouraged to see it appears to be safe.

Many researchers think patients with mild to moderate Alzheimer's disease are too far gone to have any significant benefit from drugs like bapineuzumab.

Salloway says he is hopeful the drug will work, but he will not fret if the late-stage results do not improve symptoms.

"I don't think it would kill the drug or the amyloid hypothesis," he said. Drugs like bapineuzumab remove deposits of beta amyloid from the brain, on the theory that will help improve memory problems in people with Alzheimer's disease.

Despite several attempts, no anti-amyloid drug has shown a benefit, but all of them have been tried in people with more advanced disease.

Researchers are now looking for safe ways to test people in the earliest stages of Alzheimer's, in some cases even before symptoms appear.

J&J and Pfizer are developing bapineuzumab jointly. Elan Corp ELN.I, one of the drug's original developers, still retains a financial stake.

(Editing by Bernard Orr)

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