Alzheimers Angst Builds For Elan, Wyeth as Adversary Drugs Fail
More than a dozen drugs now in human testing were designed to slow progression of the illness by blocking the proteins that form clumps in the brain. While the medicines may reduce the levels of this substance, they have shown little sustained ability to improve memory or mental function. And a more complex picture is emerging from laboratories: the beta amyloid protein that scientists think kills neurons isnt always bad.
“Drug companies are betting billions that beta amyloid is a cause of Alzheimers, and I desperately hope they are right,” Paul Rosenberg, assistant professor of psychiatry at Johns Hopkins University School of Medicine, said in a telephone interview. “My optimism is somewhat tempered because Im not sure our hypothesis is really solid.”
Treatments are urgently needed as the number of dementia patients worldwide is expected to swell to 120 million by 2050, according to Anders Wimo, professor at the Alzheimers Disease Research Center at Karolinska Institute in Stockholm. In the U.S., almost 73,000 people died from the illness in 2006, a 47 percent increase in just six years, according to the Alzheimers Association. Now, no drugs can stop the disease.
Researchers announced setbacks with experimental treatments from GlaxoSmithKline Plc, AstraZeneca Plc, Martek Biosciences Corp., Johnson & Johnson, Abbott Laboratories and Myriad Genetics Inc. at the International Conference on Alzheimers Disease in Vienna last week. The trials used a variety of approaches, ranging from nutritional supplements to nerve cell receptors. All failed to improve symptoms or slow the disease.
Frustrated
“Despite 20 years of really committed approaches to new therapies, it has not proven easy to develop new standard-of- care treatments,” said Randy Schiffer, director of the Cleveland Clinic Center for Brain Health. “Everybody is frustrated about that. Maybe were starting these trials too late, maybe we dont fully understand the disease, maybe were not following people long enough. Its a matter of concern to all of us.”
After these failures, the most highly anticipated therapy is Dublin-based Elan and Wyeths bapineuzumab, which analysts predict may generate $5 billion in annual sales if it can avoid the setbacks that have plagued the field. Elan and Madison, New Jersey-based Wyeth have begun the final phase of testing and data from the trial “may be available in the second half of 2010,” Elan spokeswoman Niamh Lyons said July 16 in an e-mail.
Bated Breath
“Everyone is waiting with bated breath on bapineuzumab,” said Michael Gold, London-based Glaxos vice president of neurosciences, in an interview. “If that one fails, then everyone will say we have to rethink the amyloid hypothesis.”
Bapineuzumab showed no benefit for most patients in an earlier study, though it slowed memory loss better than existing treatments for those without a genetic predisposition to the disease. The final trial groups patients based on genetic makeup to pinpoint how people respond to the drug. Johnson & Johnson bought access to Elans Alzheimers program with a $1 billion investment earlier this month.
Companies are looking to fight the disease with more than 600 drugs in development. Four of the seven medicines in the final stage of testing aim to treat Alzheimers by reducing amyloid levels. In addition to the Elan and Wyeth medicine, Eli Lilly & Co. has two drugs that attack the protein through different routes. Baxter International Inc. also has a late- stage therapy.
An earlier study of Lillys LY450139 compound showed that it reduced the amount of beta amyloid in the blood. Another of the companys experimental medicines, LY2062430, kept the protein from clumping in the brain in an earlier test. A study of Baxters Gammagard, which has been approved to treat an immune disorder, showed that patients taking the medicine did better on tests of mental and physical functioning than those taking a placebo.
The amyloid hypothesis is a leading theory for how Alzheimers disease develops and progresses. Named for the protein that is the main component in the plaques found clogging the brains of patients during an autopsy, recent scientific findings show its an active molecule with some beneficial properties.
Researchers studying beta amyloid found it may be a byproduct of the synaptic transmission thats essential for learning and memory. Advanced imaging technologies that accurately measure amyloid in the brain find up to 20 percent of the elderly with no memory problems have amyloid plaques, studies at the meeting showed.
Striking Results
Further clouding the picture last week was Pfizer and Medivation Inc.s experimental drug Dimebon. It has posted some of the most striking results in slowing disease so far, leading some doctors to consider findings with the medicine once sold in Russia as an allergy drug as too good to be true. In mice, it raised amyloid levels.
“This certainly causes one to question whether we should be aiming for amyloid lowering agents,” said lead researcher Samuel Gandy, associate director of the Alzheimers Disease Research Center at Mount Sinai School of Medicine in New York, who has worked on understanding the action of the protein in the brain for two decades. “It makes me wonder whats going on in these patients long-term.”
The illness typically begins with mild forgetfulness and worsens until patients forget how to brush their teeth, change their clothes, or recognize once-familiar people. Ultimately, they become confused and agitated and eventually require constant care, the U.S. National Institute on Aging says.