Johnson & Johnson (JNJ) and Pfizer Inc. (PFE)’s bapineuzumab, an experimental drug that failed to help Alzheimer’s symptoms in a study, showed signs of reducing physical damage in the brain, according to a deeper analysis.
The medicine lessened a measure of nerve cell damage in the brain and the buildup of amyloid plaque, hallmarks of Alzheimer’s, in people who are genetically predisposed to the disease, the research found. Test results released last month showed that bapineuzumab and a similar drug from Eli Lilly & Co. (LLY), solanezumab, didn’t improve patients’ memory or thinking.
Today’s report at a medical meeting in Sweden renews hope that medicines designed to attack amyloid may be beneficial when given before irreparable harm occurs to brain cells, said Reisa Sperling, a professor of neurology at Harvard Medical School. U.S.-funded studies testing the theory in high-risk people are being planned and may take three to five years to complete.
“The disease begins 10 to 20 years before there are any symptoms, and now we are better at detecting some of those changes,” said Steve Salloway, director of Neurology and the Memory and Aging Program at Butler Hospital and professor of neurology at Brown University in Providence, Rhode Island. “Drugs like this that lower amyloid will probably have their greatest impact earlier on. We have to test that.”
Pfizer gained less than 1 percent to $24.17 at the close in New York while J&J also rose less than 1 percent to $68.20. Pfizer has increased 32 percent in the past 12 months, while J&J has advanced 7.2 percent.
Drugs to slow the progression of Alzheimer’s disease could have created a market worth $20 billion, said Barbara Ryan, an analyst with Deutsche Bank, in a June note to clients. It will take years for additional studies to determine if the drugs prevent disease when given earlier, eating into their patent lives. A positive result would create an even larger market as more people take the medicines for longer.
The research led by New Brunswick, New Jersey-based J&J was presented at the European Federation of Neurological Societies meeting in Stockholm. Two additional clinical trials conducted outside the U.S. by New York-based Pfizer were halted last month. The companies are still studying a version of the drug that’s given as a shot, rather than intravenously.
The findings are weak and at best suggestive that targeting amyloid may be beneficial, said Erik Gordon, a professor at the University of Michigan’s Ross School of Business, in an e-mail. While the idea that amyloid is a trigger for Alzheimer’s disease is popular, it hasn’t been proven, he said.
“We are so desperate, given the failures in Alzheimer’s, that we cling to the slimmest threads,” Gordon said. “Trials that are failures but not total failures are considered successes.”
There are about 5.4 million Americans with Alzheimer’s disease, and the number is expected to surge as the population ages, according to the Alzheimer’s Association. The only drugs available currently for the condition temporarily treat its symptoms, rather than slowing or reversing it the brain-wasting disease.
One study involved about 1,100 people with mild-to-moderate Alzheimer’s who had a gene known as ApoE4 that puts them at risk for the condition and leads to increased amyloid buildup.
Patients getting bapineuzumab had significantly less amyloid in the brain on advanced imaging tests and lower levels of phospho-tau in their spinal fluid, a marker of nerve cell injury, said Sperling, who led one of the studies.
The drug didn’t appear to slow brain shrinkage, the study found. About 15 percent of patients getting bapineuzumab developed a condition marked by fluid leaking into the brain from blood vessels, compared with 0.2 percent of placebo patients. Most had no symptoms, and many were able to resume taking the drug after a break in treatment. Seizures were also more common in the drug-treated patients.
Six bapineuzumab patients developed cancer and died, compared with none of those getting a placebo, the study found. A panel of safety experts reviewed the cancer finding and looked at the results of other studies as well. No one cancer stood out and the increased risk ebbed when the data from all the research was collated, Sperling said.
Bapineuzumab is affecting the brain at the intended target and may influence the biology of the disease, Sperling said. Declining levels of phospho-tau, also a chemical sign of Alzheimer’s progression that is measured in cerebral spinal fluid, are compelling, she said.
“We have seen that in people who are already in advanced stages of Alzheimer’s, it’s very hard to move this disease,” said Maria Carrillo, the Alzheimer’s Association’s director of medical and scientific relations. “The scientific community is recognizing that the potential we are looking for, a delay in the disease progression, may come if we go earlier.”
Doctors are getting new tools that allow them to peer into the brain to detect Alzheimer’s disease based on amyloid buildup that starts years before symptoms. Amyvid from Indianapolis- based Lilly won U.S. approval earlier this year to help spot the protein deposits that previously were found only during autopsy. General Electric Co., based in Fairfield, Connecticut, says it will file for a similar product by the end of 2012.
The researchers haven’t yet analyzed the data to determine whether patients with the mildest symptoms, presumably earlier in the disease process, fared better than those with moderate levels of dementia, Salloway said. Additional analysis for biological markers of the disease also is under way, he said.
The second study, involving 1,331 patients without the ApoE4 gene, included two different doses of bapineuzumab. The researchers found no differences in amyloid buildup, phospho-tau or brain volume, Salloway said.
Patients getting the higher dose had lower phospho-tau levels and there was a trend in the imaging scans for less amyloid buildup in the brain, Salloway said in a telephone interview. The risk of fluid buildup and bleeding in the brain and seizures rose in conjunction with the drug dose, though there weren’t more cancer deaths in bapineuzumab patients.
While patients in the study were considered to have mild or moderate dementia, it’s important to fully understand what that means, he said.
“It’s mild in the degree of dementia, but it’s not mild in terms of what is happening in the brain,” he said. “To be diagnosed with dementia, you have to have significant impairment and neuronal injury.”
The idea that amyloid triggers a cascade of events that damage the brain is the leading hypothesis for the cause of Alzheimer’s disease, said Ronald Petersen, a neurologist at the Mayo Clinic in Rochester, Minnesota.
Now researchers need to determine if stopping the amyloid earlier will improve the health of patients, he said.
“This is encouraging, but the proof is in the pudding down the road here,” he said in an interview. “Now we need to determine if it has a biological effect that leads to prevention.”
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