Big Pharma Targets Alzheimer's

This degenerative brain disease will claim even more victims in the coming decades. Drug companies are racing to improve treatments and find a vaccine

Approximately 5 million Americans currently suffer from Alzheimer's disease, and medical experts foresee that number growing to more than 16 million by 2050. It is already the seventh-leading cause of death in the U.S., according to the National Center for Health Statistics. It's no surprise that the health-care industry is carefully studying the disease to determine its causes, in hopes of finding a cure or remedy.

The disease is most prevalent in people over the age of 70, though early-onset Alzheimer's can attack people younger than 65. For people over the age of 85, the risk of developing Alzheimer's is 50%. Many medical professionals believe the increased incidence of Alzheimer's can be linked directly to longevity. In other words, simply because people are living longer lives than they used to, they are more likely to suffer from old-age diseases including Alzheimer's.

But that doesn't mean the medical research community is complacent or unconcerned. While efforts to develop a cure are still very much in early stages, several small biotechnology and larger pharmaceutical companies are already testing drugs and compounds to stem the spread of this disease. Five Food & Drug Administration-approved drugs are already available for Alzheimer's patients. Researchers are busily developing different versions of these existing drugs, as well as new treatments for the disease.

Cause and Effect

To find ways to attack the disease, scientists must first understand what causes it. Most Alzheimer's research is still very much in its infancy. Alzheimer's was first identified in 1906. Autopsies of the first identified victim—and many subsequent victims—show significant shrinkage of the cortex, the part of the brain associated with memory and speech.

The autopsies also show a buildup of fatty deposits and plaque, consisting of a protein called beta-amyloid. This plaque fills in the spaces between the brain's nerve cells in Alzheimer's patients. Many medical researchers believe this plaque disrupts normal "communications" between brain cells. Some believe the plaque also keeps cells from regenerating themselves, leading to the shrinkage seen in the brains of those with Alzheimer's. Many Alzheimer's research efforts are centered on clearing the beta-amyloid buildup from the brain or, preferably, preventing it in the first place.

Breakthrough Studies

Eli Lilly (LLY; S&P investment rank 3-STARS; hold: $57), for example, is currently in phase II trials for its compound, LY2062430, which the company hopes can slow the buildup of beta-amyloid.

Investigating a widely held scientific theory that the buildup of beta-amyloid takes place because of a deficiency of an essential brain messenger chemical, called acetylcholine, Wyeth (WYE; 3-STARS; $46) has developed a compound, called lecozotan (SRA-333), to increase levels of acetylcholine—and another nerve-cell communication chemical, glutamate—in Alzheimer's patients. This compound is in phase II trials.

A phase III study sponsored by Martek Biosciences (MATK; 3-STARS; $27) and the National Institute on Aging is testing whether the omega-3 fatty acid, docosahexaenoic acid, can slow cognitive and functional decline in people with mild to moderate Alzheimer's disease.

A phase II study sponsored by Memory Pharmaceuticals (MEMY; $2) is testing whether MEM 1003, a drug that helps regulate brain calcium levels, is helpful in mild to moderate Alzheimer's disease.

Myriad Genetics (MYGN; $47) is in the midst of a phase III trial of its compound, Flurizan, which the company calls the first in a new class of drugs known as selective amyloid-lowering agents, or SALAs. Other SALAs are in development.

Room for Improvement

While these new treatments are studied, existing treatments are being explored for ways to improve their efficacy. The five FDA-approved Alzheimer's drugs are Aricept, developed and sold by Eisai and Pfizer (PFE; 3-STARS; $25); Exelon, from Novartis (NVS; 5-STARS, strong buy; $55); Razadyne, from Johnson & Johnson (JNJ; 4-STARS, buy; $64); Cognex; and Namenda, from Forest Laboratories (FRX; 4-STARS; $38). (Although it was the first to win FDA approval, Cognex is seldom prescribed today because it is associated with increased risk of liver damage.)

The first four are cholinesterase inhibitors, and they work by preventing the breakdown of acetylcholine. The fifth, Namenda, works by regulating the activity of glutamate in the brain and nervous system.

There are many clinical trials, in different phases, testing these existing compounds in different formations and dosages or in conjunction with other drugs—all in the quest to find a cure for Alzheimer's.

Potential Vaccines

At the same time, there is much work being done to develop a vaccine against Alzheimer's. Such a vaccine can't come soon enough for some people; the risk of developing the disease increases significantly if one has a parent or sibling suffering from it.

In 2000, Wyeth and Elan Pharmaceuticals (ELN; $19), an Irish biopharmaceutical company, started a clinical trial of a vaccine that stimulates beta-amyloid antibodies. The trial was halted when several of the participants developed severe inflammation of the brain. However, the researchers noted that patients did show a significant slowing of cognitive decline. The two companies are now testing a revised version of the vaccine, which, they hope, will not cause brain inflammation.

Meanwhile, Merck (MRK; 4-STARS; $51) is testing V950, another potential vaccine, in a phase I trial. This compound is intended to prevent the buildup of beta-amyloid before it interferes with the brain's communication systems.

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