When 70-year-old Bill Price signed on in 2006 to become one of the early testers of the Alzheimer’s drug bapineuzumab, he held high hopes the injections would stop the disease that was starting to claim his memory.
Intended to eliminate plaques in the brain that are a hallmark of the illness, bapineuzumab is a project of Johnson & Johnson, Pfizer Inc. and Elan Corp. The three companies are racing Indianapolis-based Eli Lilly and Co. to market the first broadly available drug designed to target a cause of Alzheimer’s, rather than just its symptoms.
For Price, the drug was a disappointment. He left the trial early after experiencing headaches and hallucinations, side effects that may have been due to brain swelling. Such drawbacks aren’t the only issue facing bapineuzumab. Early data suggests that even if it shrinks plaques, the drug may not greatly aid cognition. Price is hopeful the study’s final data will show that other patients were helped though he was not.
“I see the handwriting on the wall,” Price, a former teacher who lives in Opelika, Ala., said. “I’m desperately trying to do whatever I can to keep the disease in check. I feel the onslaught.”
While details of late-stage data on the two drugs aren’t scheduled to be reported before October, the therapies will be discussed among researchers and geriatric specialists at next week’s Alzheimer’s Association International Conference in Vancouver, according to William Thies, the chief medical and scientific officer of the Chicago-based Alzheimer’s Association.
Patients, doctors, drugmakers and investors share Price’s sense of urgency. If the drugs work well, they could be paired with recent testing advances to alter the landscape of health care in the U.S., curbing an illness that may affect 16 million Americans by 2050, an increase from 5.4 million now, according to U.S. health officials. In 2012, the cost of care for those with the disease will be $200 billion, the association said.
“Alzheimer’s disease ends your dignity, separates you from all your resources and torments your family,” Thies said in a telephone interview. “There is more and more concern that we can’t afford the end stage that we are going to experience in the middle of the century. Its impact on various segments of the economy is becoming clearer and clearer as the cost it presents to Medicare and Medicaid goes up.”
The treatments may help reinvigorate an industry grappling with patent losses estimated to wipe out $171 billion in sales by 2015, according to research group IMS Health, based in Norwalk, Connecticut. The market could quickly exceed $10 billion a year, said David Heupel, a Minneapolis, Minn-based portfolio manager with Thrivant Financial for Lutherans.
“In large-cap health care, that’s about as big as it gets,” Heupel said.
If the drugs fail, it may be years before the next promising therapy comes into focus.
Mark Schoenebaum, an analyst at the ISI group in New York, gives only a 25-percent chance of approval for bapineuzumab from New Brunswick, N.Y.-based J&J, New York-based Pfizer and Elan, based in Dublin. Indianapolis-based Lilly’s solanezumab has a 15-percent chance, he said.
The drugs 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.
Bapineuzumab and solanezumab “represent a crucial test of the current dogma,” said Jordan Holtzman, a professor of medicine at the University of Minnesota in Minneapolis. “If they fail to show a significant benefit, it would be imperative for the pharmaceutical industry to search for new models.”
The only therapy on the immediate horizon that has shown success against the illness in mid-stage human trials is Baxter International Inc.’s Gammagard, an expensive, relatively scarce treatment derived from donated blood plasma that replaces antibodies in people whose immune systems can’t protect them from infection.
It’s not clear precisely how Gammagard, on the market for years, works against Alzheimer’s. Early results suggest it may raise the level of antibodies to beta amyloid in the blood and spinal fluid of patients. The Deerfield, Illinois-based company is betting the result will be to slow or stop the disease and a final-phase study may be completed next year.
Another approach targets the tau protein that was first characterized in 1975. By the mid-1980s, it was thought to play a role in some brain disorders. It wasn’t until the 1990s, though, that evidence began to accumulate that tau deposits more closely reflected a patient’s mental state than beta amyloid plaques.
In its healthy form, tau helps supply nutrients to cells in the brain. When damaged, it becomes tangled, chopping off the supply lines and becoming part of the mass of plaques seen in the brains of people with the disease.
A closely held company, TauRx, based in Singapore, is developing drugs based on the tau model. TauRx’s tau aggregation inhibitors have been tested in Phase 2 clinical trials, and the company plans to make an announcement about its Phase 3 clinical trials later this year, said Claude Wischik, the executive chairman and co-founder of the company.
Other theories are being explored, including malfunctioning mitochondria, the part of cells that convert nutrients into energy. The brain may also start using insulin inefficiently, leading some to speculate the condition is “diabetes of the brain.” Others are examining whether the coating that protects nerves in the brain, called myelin, has been damaged.
Even if bapineuzumab and solanezumab are found in the latest studies not to work, they shouldn’t be dismissed, said Randall Bateman, a professor of neurology at Washington University School of Medicine in St. Louis.
The findings may just be a reflection of bad timing, while the brain-swelling that chased Bill Price away from the trial may be an immune reaction that must be monitored but will likely dim over time, Bateman said.
The drugs may have been given “too late, after other degenerative processes have already begun or there’s too much damage done,” he said
It’s like treating a heart-attack patient with a cholesterol-lowering statin, he said: While that may prevent future damage, it doesn’t reverse trauma that already occurred.
Trials are being planned to evaluate whether earlier intervention will help people who are at added risk for Alzheimer’s due to family history or because they carry certain biomarkers for the disease without showing impairment. Those trials will be discussed at the Vancouver meeting, he said.
The impetus for the newer studies is that it’s still not clear when it’s best to begin treatment, said Bateman, who is an investigator in the planned clinical trials. Brain changes that presage Alzheimer’s begin about 15 years to 20 years before patients become symptomatic.
The trials involving bapineuzumab and solanezumab “will be very valuable whether the drugs work or not,” said Thies of the Alzheimer’s Association. “If they work, that leads us relatively quickly to a therapeutic. There would be great pressure to treat people as early as possible, to stabilize them at the highest quality of life possible, and lower costs because they won’t need as much care.”
If they don’t work, “it rapidly tells us that maybe we need to change the way we are using these medications or the kinds of medications we are testing.”
Price, who taught English as a second language on an Indian reservation in Arizona before retiring to Alabama, has an early stage of the disease, he said. He is still able to drive, help shop and prepare meals and contribute to his family.
If an effective treatment is found quickly, he and others with a similar stage of the disease are most likely to benefit. If not, he says he will try to participate in other clinical trials.
“I feel like before I go into oblivion, I want to help other people and maybe even help myself if it’s not too late,” Price said. “I want to help find an answer to the Alzheimer’s dilemma.”