Drug makers enter crucial phase in search for Alzheimer’s disease treatments
Reporting from Chicago — After decades of research and multiple failed attempts to find a treatment, the pharmaceutical industry is entering a crucial phase in the search for a drug that can slow, or stop, the progression of Alzheimer’s disease.
Drug makers see huge moneymaking potential because of the aging population. Alzheimer’s afflicts more than 5 million Americans and is one of the leading causes of death in the United States, according to the Centers for Disease Control and Prevention. The market of patients globally is estimated to rise from about 30 million in 2010 to 120 million by 2050, opening the door to billions of dollars in sales.
There are an unprecedented five drugs being developed to modify the insidious disease that are in the Phase 3 final stage of U.S.-approved clinical trials. These “interventional drugs,” if approved, would be markedly different from what’s available, including Pfizer Inc.’s much-promoted Aricept, which temporarily treats symptoms of Alzheimer’s.
Exactly when one of these experimental treatments might be submitted to the U.S. Food and Drug Administration for approval is unclear, and there is no guarantee they will reach consumers. But researchers and some Wall Street analysts are speculating that a disease-modifying product could be on the U.S. market within five years.
“This is really the last stage of scientific study before you actually have a product to put on the market,” said William Thies, chief medical and scientific officer for the Alzheimer’s Assn. “It’s really an important mark as to how far we have come. You are now seeing the first maturation of the development of the second-generation of drugs for Alzheimer’s disease.”
One such product being watched closely is a biologic drug derived from plasma that is sold by Deerfield, Ill.-based Baxter International Inc. as a treatment for immune system disorders.
Last month, researchers led by Dr. Norman Relkin from New York-Presbyterian Hospital/Weill Cornell Medical Center presented a 24-patient study that showed Baxter’s drug, Gammagard, as having promise as an effective therapy for Alzheimer’s patients. Researchers saw a reduced rate of brain shrinkage and improved “thinking abilities” in the 16 patients in the trial who received Gammagard intravenously. Baxter plans to expand the research in a final-stage U.S. clinical trial.
The idea behind Baxter’s drug is that it can help the body’s immune system to clear the brain of amyloid, a sticky, plaquelike substance thought to be key in the development and progression of Alzheimer’s.
Jason Marder, 67, and his wife, Karin, of New York, believe his twice-monthly Gammagard infusions have helped to slow the disease since he started receiving them in 2006 as a patient of Relkin’s in the clinical trial.
“The incredible thing is that there has been no decline in Jason,” said Karin Marder, his wife of 17 years.
The Marders understand that no one can be sure it’s the drug that allows him to enjoy an active lifestyle. And they know about the risks of Gammagard for elderly patients, including heart attack or stroke, and side effects such as rash or changes in blood pressure, doctors say.
The Marders say they’re willing to take the risks after having witnessed the devastating effects of the disease on Jason Marder’s brother, who died in his late 40s.
“I had noticed changes in Jason that were not the normal aging process,” Karin Marder said. “I would be sitting with him and he would say, ‘Didn’t we go to a great movie last night?’ And I would say, ‘We did not go to a movie last night.’ ”
Jason Marder continues to have similar forgetful conversations. But his wife thinks the episodes would be more frequent and that he would be less independent if he hadn’t been on Gammagard. Seven years since being diagnosed with Alzheimer’s, Jason Marder continues to take the subway from their Manhattan home, go grocery shopping and prepare meals on his own.
“I was close to his brother, Mitchell. We knew the progression, and it was absolutely devastating,” Karin Marder said. “I have seen the decline, and Jason is no longer in decline. With the baby boomers now, this is going to be an epidemic, and we have to do something about it.”
Baxter is not alone in its hunt for an Alzheimer’s therapy. The world’s largest drug companies also have disease-modifying Alzheimer’s treatments in Phase 3 trials and are investing hundreds of millions of dollars in research.
New York-based Pfizer is collaborating with a subsidiary of New Jersey-based giant Johnson & Johnson to research, develop and commercialize products to treat or prevent neurodegenerative conditions. The venture’s lead compound is bapineuzumab, which uses antibodies to remove amyloid.
“Our bapineuzumab program is a modifying therapy [being studied] with hopes of modifying the course of Alzheimer’s,” said Dr. Steve Romano, a Pfizer vice president and head of medical affairs for the company’s primary care business.
Despite a study two years ago that linked the drug to brain swelling, Pfizer has forged ahead with patient trials of bapineuzumab. The J&J-Pfizer venture hopes to ramp up clinical trials to study up to 4,000 patients worldwide. Analysts say North American trials could be completed in 2012, but the company is not speculating on a potential submission to the FDA.
Pfizer knows the risks too well. In March, a study of Pfizer’s once-promising Alzheimer’s drug Dimebon showed that it was no more effective than a placebo in a Phase 3 study. Pfizer said it was continuing to evaluate Dimebon as a possible Alzheimer’s treatment.
“Even though there have been failures, you have to consider you are looking at novel mechanisms and trying to take the treatment to another level,” Romano said. “There are risks, but they are worth it.”
The last three years have brought other high-profile failures in late-stage trials, such as the drug Flurizan, developed by Myriad Genetics Inc., and Neurochem Inc.’s Alzhemed.
Baxter Chief Executive Bob Parkinson calls the Gammagard-Alzheimer’s project a “wild card,” but analysts who follow the company see it as potentially a blockbuster that could one day generate more than $1 billion in annual sales.
Baxter is proceeding with caution, which industry analysts say is warranted given the study of Gammagard has been on so few patients. A larger study of 360 patients in more than two dozen sites across the country and a recently announced concurrent study over the next two to three years will reveal more about Gammagard’s future as an Alzheimer’s treatment.
“While the Phase 2 results are encouraging for patients who have few clinical options, the sample size was small, and we will need to wait for results from the two Phase 3 studies to have a clear sense of the clinical benefit from this treatment,” said Ben Andrew, an analyst with Chicago investment bank William Blair & Co.
Even faced with the prospect of additional failures, researchers say continued study will help the medical community better understand how drugs can affect the progression of Alzheimer’s. The Weill Cornell trial of Baxter’s drug used magnetic resonance imaging of patients’ brains to provide a more definitive measure showing “less whole-brain atrophy.”
“The use of MRI technology gives us encouragement that the combination of traditional clinical test outcomes and biological markers like those from brain imaging can facilitate Alzheimer’s clinical trials,” Relkin said. “The [use of MRI technology] may increase the accuracy of the tests themselves. This may spur other trials.”
