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Potential Alzheimer’s drug fails first of four key trials

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Pfizer Inc., Johnson & Johnson and Elan Corp.’s experimental Alzheimer’s treatment failed to improve symptoms of dementia in the first of four pivotal studies testing the drug.

Bapineuzumab, designed to target the brain plaques that serve as a hallmark of Alzheimer’s, didn’t aid cognitive or functional ability in patients who carry a gene, called ApoE4, that makes them more likely to get the disease, Pfizer said Monday in a prepared statement. Doctors now await results from trials in patients without the higher genetic risk.

Bapineuzumab is in a race with a similar product from Indianapolis-based Eli Lilly and Co. to become the first therapy to target a cause for Alzheimer’s, rather than just its symptoms. While patients in the failed study, dubbed 302, have now been taken off the drug, the other trials will continue, New York-based Pfizer said in its statement.

“There was no reason to believe, unless there was a miracle, that this would be positive,” said Rudolph Tanzi, professor of neurology at Harvard Medical School in Boston. “It will only be the results of the non-ApoE4 carriers that will inform us about the future.”

Both bapineuzumab and the Lilly drug work by slowing the production of beta amyloid, the protein that makes up the plaques. Since research began on these drugs, other theories of the disease have developed, including activity by a protein called tau that tangles in the brains of patients.

It’s still too early to determine which therapy may work best to eliminate the disease, researchers said,

“While we are disappointed in the topline results of Study 302, a more complete understanding of bapineuzumab and its potential utility in mild-to-moderate Alzheimer’s disease will be gained,” said Steven Romano, Pfizer’s head of medicine development for primary care, in the statement.

The first Alzheimer’s drugs, should they prove successful, would lead to a market for the treatments worth $20 billion, according to Barbara Ryan, an analyst with Deutsche Bank, in a June note to clients.

The companies are conducting trials in two groups of patients, in four total studies. The data outlined Monday were from U.S. patients with the ApoE4 gene, who tend to show symptoms of Alzheimer’s earlier in life.

Researchers haven’t been optimistic that the drug would be effective in patients with the gene, said Tanzi.

Patients with the Alzheimer’s gene didn’t benefit from treatment in earlier studies, and they were given a lower dose because of side effects, he said in a telephone interview.

The companies will “expedite the completion” of a second study in patients with the gene outside the U.S. That data should come this summer, said Mackay Jimeson, a Pfizer spokesman, and the companies will do additional analyses of patients in the failed study.

Full data are expected in September, when the companies have said they will present findings from people without the ApoE4 gene in Stockholm at the European Federation of Neurological Societies meeting.

“While we are disappointed in the results of this first study, the phase 2 trials suggested that ApoE4 non-carriers may have a better chance of benefiting from bapineuzumab than ApoE4 carriers, and the results of the second study in non-carriers due later this summer will shed more light on this possibility,” J&J spokesman Bill Price said in a statement.

Pfizer decided to announce the trial had failed now because it had patients stop taking the drug and was concerned news would leak out before it could complete other trials, Jimeson said. The companies previously said that they would release results from the two U.S. studies at the same time.

The failure was no surprise, said Mark Schoenebaum, an analyst with ISI Group in New York. “Our current model carries a 25-percent probability of success,” he said in a client note.

The Pfizer-J&J drug and the one from Lilly are based on one of the first research strategies designed to combat the disease.

After autopsies of Alzheimer’s victims showed an accumulation of beta amyloid plaques in their brains, drugmakers began focusing on that as a potential cause. Since then, other contributing factors have surfaced, including the overdevelopment of a different protein, known as tau.

While most of the strategies currently in the third and final stage of testing required for regulatory approval target amyloid, the field is now moving beyond amyloid-only targets, said Maria Carrillo, director of medical and scientific relations for the Alzheimer’s Association.

There are more than 40 different compounds currently in mid-stage tests for the disease, according to an accounting from the association.

“We don’t think amyloid is going to be a magic bullet, but it is important,” Carrillo said in an interview at the association’s annual meeting last week. “This is a maturing field with a variety of approaches, and we’re going to need multiple approaches. We feel very hopeful about the maturation of the field and the variety of approaches in development.”

One main complaint about the current studies with bapineuzumab and Lilly’s drug solanezumab is that they were given to patients who already displayed dementia.

New research shows that amyloid build up begins decades before symptoms start, leaving patients potentially too damaged to benefit from treatment. Studies are now planned to test treatments in people at risk for the disease before signs of dementia appear, based on brain imaging scans, age and genetics.

“We know a heck of a lot more now than we did 15 years ago, when the first studies of bapineuzumab were being designed,” Carrillo said prior to the latest findings being released. “We are slowly moving the needle back in time for these amyloid plaque busters.”
 

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