Biotech Values

[DewDiligence]

Tuesday’s WSJ reviews some Alzheimer’s drug candidates in early and mid-stage development:

[For other discussions of AD, please see #msg-2797088, #msg-2829448, #msg-2872262, and #msg-2836718. Sorry –no link for today’s WSJ article.]

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A New Approach
To Fighting Alzheimer's

Major Clinical Trial Is Set
To Begin, as Wave of Drugs
Aims to Halt the Disease

By ANDREA PETERSEN
Staff Reporter of THE WALL STREET JOURNAL
June 29, 2004

In a significant advancement for the next generation of Alzheimer's treatments, Neurochem Inc. says it will begin recruiting patients for a large efficacy trial of its drug Alzhemed in the next few weeks.

The drug is at the leading edge of a wave of coming treatments that offer some hope to the 4.5 million Americans struck with the memory-robbing illness. Unlike current drugs, which generally treat the symptoms of Alzheimer's, the new drugs target the underlying illness itself. The aspiration is that these medicines will be able to halt the devastating progression of the disease -- or prevent it entirely.

Alzhemed, which helps prevent the formation of the plaques many scientists believe are the culprit in Alzheimer's disease, could be on the market within four years. The new study will enroll 950 patients over 18 months, at 70 sites in the U.S. and Canada.

Eli Lilly & Co. is at an earlier stage in its testing of a drug that inhibits an enzyme involved in plaque formation. That drug is in early trials and could be available to consumers in three to five years. Further down the road are so-called vaccines that aim to clean out the plaques after they have formed in the brain. Eli Lilly and Wyeth are working on such treatments.

At the same time, researchers are conducting large clinical trials of existing drugs, vitamins and herbs to see if they might be useful in combating or preventing Alzheimer's. For example, data suggest that people who have taken cholesterol-lowering statins and anti-inflammatory drugs for arthritis have a lower incidence of Alzheimer's disease. And the Chinese herb huperazine has been found to have many of the same properties as certain Alzheimer's drugs.

A new drug called memantine, sold under the brand name Namenda, was approved in the fall by the Food and Drug Administration. Memantine reduces excess levels of the brain chemical glutamate, an action which may help prevent brain-cell death. Physicians who have been using it in their patients say the drug can slow cognitive decline somewhat, but the impact hasn't been significant. [Sales have been pretty good, however.] Memantine was developed by Merz GmbH of Germany and is marketed in the U.S. by Forest Laboratories Inc.

"For a long time [Alzheimer's research] was a depressing area," says Steven Ferris, director of the Alzheimer's disease center at the Silberstein Institute for Aging and Dementia at the New York University School of Medicine. "Now I think things are really starting to look promising."

New Alzheimer's Patients

The new developments come at a critical time. Alzheimer's drugs are already a $1.18 billion business, according to IMS Health, a market-research firm. [This sounds much too low and must be based on a highly restrictive definition.] And doctors expect the numbers of Alzheimer's patients to sharply increase during the coming decades, as people live longer and as huge numbers of baby boomers enter the years where they are at highest risk for the disease. By 2050, the number of Americans with Alzheimer's is expected to reach between 11.3 million to 16 million, up from the current 4.5 million, according to the Alzheimer's Association.

Much of the excitement over the new drugs is a response to the lackluster performance of existing treatments. The three veteran drugs are Aricept by Pfizer Inc. and Eisai Co.; Exelon by Novartis AG; and Reminyl by Johnson & Johnson and Shire Pharmaceuticals Group PLC. Dubbed cholinesterase inhibitors, these drugs work by boosting the levels of acetylcholine, a neurotransmitter that is important for memory and learning. In clinical trials, the drugs -- which cost about $4 a pill -- have been shown to slow the cognitive decline in Alzheimer's patients somewhat. Doctors, however, say the drugs' effects are often difficult to see. [This echoes the sentiments in #msg-2797088.]

"It doesn't take you anywhere near normal," says Claudia H. Kawas, professor of neurology, neurobiology and behavior at the University of California, Irvine.

Targeting Plaques

The new drugs target what many scientists believe is the key to Alzheimer's destructive power -- plaques made of the protein beta-amyloid that build up in the brain. The Eli Lilly drug, which hasn't been named, aims to prevent beta-amyloid from forming by inhibiting the enzyme gamma secretase. Alzhemed, the Neurochem drug, works later, by preventing strings of beta-amyloid from clumping together, an activity that has to happen to form the dangerous plaques. The vaccines from Lilly and Wyeth act later still to prevent the disease, by flushing away the plaques after they've formed.

All of the drugs have some hurdles to clear before patients could benefit. Research is continuing. And while many suspect that beta-amyloid is a critical player in Alzheimer's disease, scientists aren't certain that it is the only player. So destroying the plaques may not be enough to thwart the disease. Also, doctors are concerned about scary side effects. Already, Wyeth and Elan Corp. have halted testing of an earlier version of a vaccine after more than a dozen people developed a dangerous inflammation of the brain.

Still, preliminary data on some of the new drugs are promising. In April, Neurochem announced results of a very small study of Alzhemed with 18 patients that had mild to moderate Alzheimer's disease. The company said that 80% of its mild patients had stable cognitive function, with no decline or a slight improvement, over 16 months. Patients interested in the upcoming new trial can check out the company's Web site for more information, at www.neurochem.com.

The use of existing drugs that are approved for other uses is also a growing area of Alzheimer's research. The National Institute on Aging is in the middle of three trials testing anti-inflammatory drugs and one testing a statin. The government's Alzheimer's Disease Education and Referral Center at www.alzheimers.org has information on how to participate in any open trials. Doctors have been discouraged by a few studies that showed anti-inflammatory drugs didn't stem cognitive decline, but some researchers believe the drugs may need to be given earlier than they were in those studies.

Researchers are also studying several vitamins and herbs for use with Alzheimer's, and a variety of clinical trials are recruiting participants. The research is preliminary, but there is evidence that anti-oxidants such as vitamin E and C may help. Scientists are exploring substances such as certain B vitamins and folate that can lower blood levels of homocysteine, an amino acid linked to Alzheimer's and heart disease.

Herbal Remedies

Arms of the National Institutes of Health are studying ginkgo biloba, an herbal remedy that may have some memory-enhancing effects, and huperazine, which has similarities to the existing cholinesterase inhibitor drugs. Information on all the government trials is available at the www.alzheimers.org site.

Doctors say that no one drug is likely to emerge as a cure, and that the most effective treatment may be a combination of medications.
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