Help finally could be on the way for victims of Alzheimer’s disease.
After decades of arduous work, drug makers and academic researchers believe they’ve made considerable progress in bringing a new generation of treatments to market that may ease symptoms of the devastating brain disease and might even stop its progression.
Several compounds are in mid- and late-stage clinical trials, and the first new drugs could hit the market in as soon as three years.
“The rate of Alzheimer’s is going to explode as the baby boomers hit 65,” said Dr. Sam Gandy, a leading researcher at Mount Sinai Medical Center and chairman of the Alzheimer’s Association’s medical board.
The current size of Alzheimer’s-drug market is an estimated $3 billion, with up to 12 million people suffering from the condition in the U.S., Europe and Japan. The market could possibly surpass $20 billion if the newer drugs prove to be highly effective, according to UBS analyst Roopesh Patel.
The key growth driver for Alzheimer’s drugs is undoubtedly an aging population.
When Dr. Alois Alzheimer, a German physician, identified the disease in early 1900s, he described the illness as rare. But at that point, the average American’s life expectancy was 50. Today it’s 78.
Today about 5.2 million Americans suffer from the neurological disease. About 13% of all people aged 65 and over are believed to be afflicted, with that number rocketing to about 50% at age 85. By 2030, an estimated 7.7 million will be living with the disease, according to the Alzheimer’s Association.
That’s grim news for American families. Because Alzheimer’s patients eventually require some type of round-the-clock care, having a family member stricken with the disease can be a heavy burden, emotionally and financially. And although many patients do end up spending their final days in a nursing facility, an estimated 70% are cared for at home.
“When half of the baby boomers over 85 years old become demented, it’s going to create a crisis,” said Gandy. “The cost of Alzheimer’s will break the bank of Medicare.”
Only four drugs have been approved to treat Alzheimer’s in the U.S., and they come with limitations. They’re generally capable, at best, of boosting memory for up to 18 months. After that, patients continue to decline as the disease progresses.
Disease-arresting drugs, however, would be a game changer. If they work, doctors could administer the drugs during the earlier stages of the disease, when brain damage caused by disease is still manageable. The drugs could then be used to keep the disease in check, giving patients the prospect of going on to live relatively normal lives.
Eli Lilly & Co. (LLY), Baxter International (BAX) and Medivation (MDVN) all have candidates in Phase III clinical testing. Wyeth (WYE), along with partner Elan Corp. (ELN), has said it still plans to persevere with Phase III trials for its candidate, despite some high-profile setbacks. GlaxoSmithKline (GSK) and partner Epix Pharmaceuticals (EPIXD) are in Phase II testing with their drug candidate, as is Australian-based Prana Biotechnology Ltd. (PRAN).
But the path to success hasn’t been an easy one for researchers.
In June, Myriad Genetics (MYGN) was forced to pull the plug on the hotly anticipated Alzheimer’s drug Flurizan after a Phase III trial showed it wasn’t effective. Myriad had spent $60 million in the first six months of 2008 alone on the product.
In late July, shares of Wyeth and Elan were hammered on mixed Phase II news for their highly-touted antibody therapy bapineuzumab. The results showed that while the drug appeared to be quite effective on some Alzheimer’s patients, it may have triggered brain swelling in a small number of other users. Wyeth and Elan are still moving ahead with Phase III trials.
The only four medications approved to treat it are Pfizer Inc.’s (PFE) Aricept, Novartis AG’s (NVS) Exelon, Johnson & Johnson’s (JNJ) Razadyne, and Forest Laboratories’ (FRX) Namenda.
All four entries essentially stoke the “firing power” of the brain cells that haven’t been destroyed yet by the disease. But while they can temporarily help patients think or remember things more clearly, they can’t stop the disease’s progression. And the drugs usually are effective for no more than 18 months.
“The current drugs out there treat symptoms of the disease,” said Dr. Eric Siemers, medical director for Eli Lilly & Co.’s Alzheimer’s program. “They can boost memory, but they don’t get to the underlying cause of the disease.”
By contrast, most of the new candidates are targeted at stopping what many researchers believe is the root cause of Alzheimer’s: a buildup of a protein called beta-amyloid, or a-beta, that is poisonous to brain cells.
While younger brains are able to keep levels of beta-amyloid in check, for reasons still unknown, some older brains lose that ability. Autopsies of patients with Alzheimer’s show their brains are riddled with piles of beta- amyloid, often referred to as plaque.
The build-up is toxic to brain cells, resulting in severe brain damage over the course of several years. Researchers estimate that Alzheimer’s sufferers lose up to 6% of brain mass every year. By interfering with beta-amyloid accumulation, researchers hope to halt that destructive process.
“The drugs we’re developing are unlike any being developed before,” said Gandy. “It’s largely uncharted territory.”
Here’s a rundown of some of the most talked about drugs in development that might be able to halt the progression of Alzheimer’s.
Lilly’s duo
Indianapolis-based Lilly (LLY) has been working on two Alzheimer’s treatments that stimulate the immune system to ward off plaque.
Currently in Phase III clinical testing, LY450139 is aimed at inhibiting an enzyme called gamma-secretase, which plays a role in the production of amyloid- beta.
Lilly is also developing an antibody-based product code-named LY2062430. On July 30, the drugmaker announced it plans to begin Phase III testing for the therapy in 2009.
Lilly added that the product, as opposed to some other antibody therapies, did not appear to trigger any treatment-related brain-swelling, bleeding or similar negative side effects.
“The Phase III drug (LY450139) slows down the body’s ability to make amyloid- beta,” explained Siemers. “The antibody helps get amyloid-beta out of the brain.”
Wyeth and Elan aim for direct hit
Madison, N.J.-based Wyeth and Irish drugmaker Elan have teamed up on two Alzheimer’s-drug candidates: an antibody treatment called bapineuzumab and a vaccine called ACC-001.
According to Menelas Pangalos, who heads Wyeth’s Alzheimer’s program, the antibody binds to a-beta plaque deposits and removes them from the brain.
“We’re hoping it stops disease progression,” said Pangalos. “We’re actually trying to hit the disease process itself.”
Pangalos said that, if all goes well, bapineuzumab could be on the market in three to five years. The drug began Phase III trials in December.
ACC-001 is intended to stimulate a patient’s immune system to manufacture antibodies that recognize a-beta in their system. The product is in Phase II testing.
Both drugs, however, have been haunted by safety concerns.
On July 29, Wyeth and Elan unveiled relatively favorable Phase II results for bapineuzumab. But the study also showed the compound was ineffective on a subgroup of patients who have a genetic mutation called ApoE4, which has been associated with an inherited form of Alzheimer’s.
Even more worrisome, a handful of bapineuzumab users, particularly those who had the ApoE4 mutation, developed brain swelling.
The ACC-001 program has also had trouble. It was put on hold earlier this year after a patient developed a potentially dangerous skin reaction. Wyeth received the green light from regulators to resume clinical testing in May.
Baxter seeks to extend immune-system drug
Deerfield, Ill.-based Baxter International (BAX) has been testing the hematology drug GammaGard as a treatment for Alzheimer’s.
Originally used to treat children with severe immune deficiencies, GammaGard is really a mélange of antibodies derived from human blood. The product is known generically as immune globulin intravenous, or IGIV.
IGIV researchers have said they think the therapy can battle Alzheimer’s by stimulating the body to generate antibodies that discourage plaque build-up.
“It’s like a gentle vacuuming,” said Dr. Norman Relkin, a leading Alzheimer’s researcher at Weill Cornell Medical Center in New York City. He added that because the product has already been on the market for decades, its safety profile has been well-established.
GammaGard is about to begin Phase III clinical trials for Alzheimer’s. According to Baxter, the company could be ready to file for regulatory approval for that indication between 2011 and 2012.
One potential downside of the product, however, is that, because it is garnered from donated blood, IGIV is often in short supply.
Relkin said the key to addressing this issue will be researchers’ capacity to home in on exactly what mechanism is at work in the blood-derived product and then try to synthesize it in a laboratory setting.
Repurposing at Medivation
Medivation (MDVN), like Baxter, is also trying to teach an old drug new tricks.
Originally approved about 25 years ago in Russia as an antihistamine, Dimebon is being tested by the San Francisco-based Medivation not only for Alzheimer’s but for the equally devastating Huntington’s disease as well.
According to Medivation Chief Executive Officer David Hung, an M.D., Dimebon works by tinkering with a cellular component called mitochondria, which plays a role in cellular death. The drug is currently in Phase III testing for Alzheimer’s.
“We’ve shown in pre-clinical trials that Dimebon inhibits neuron death,” said Hung, taking note of the 6% annual brain-mass loss Alzheimer’s patients are believed to suffer.
A recent study published in the prestigious British medical journal Lancet also found that Dimelbon users appeared to steadily improve over the course of a 12-month period, rather than just level off, as users of current medications tend to do.
Hung said the company plans to file for U.S. regulatory approval in 2010.
Epix and Glaxo’s ‘brain booster’
Lexington, Mass.-based Epix Pharmaceuticals (EPIXD) has teamed up with U.K. pharmaceutical giant GlaxoSmithKline (GSK) on a drug code-named PRX-03140.
Currently in Phase II testing, Epix researchers said they’ve been primarily testing the product as a “brain booster,” to help improve cognitive function. But they add that the drug, at least in animal studies, appears to be able to slow progression of the disease.
The company has particularly been heartened by Phase IIa results for the product, released at the beginning of the year.
“We saw significant improvement in cognition in just two weeks,” former Epix Chief Executive Officer Michael Kauffman told MarketWatch in late June. He noted that drugs currently on the market can take up to six months to have an effect.
Epix said the drug works in part by stimulating neurons that researchers believe become dormant in the brains of Alzheimer’s patients.
“The fact we’re able to get an effect that quickly indicates you’re taking the neurons that were asleep and waking them up, and also making the existing neurons work harder,” said Kauffman.
Prana aims to ‘nip it in the bud’
Australia-based Prana Biotechnology Ltd. is also diligently working on a beta- amyloid inhibitor, called PBT2.
According to Prana’s co-founder, Harvard University geneticist Rudolph Tanzi, PBT2 is based on the theory that the metals copper and zinc play a key part in the toxicity of beta-amyloid. PBT2 neutralizes toxicity of beta-amyloid by blocking the interaction with these metals.
“The product disrupts the aggregation of a-beta [beta-amyloid],” said Tanzi. ” It works in the ‘nip it in the bud’ stage, before the buildup.”
Prana released positive Phase IIa data on PBT2 in February.
SOURCE/RESOURCE: money.cnn.com on 8/14/08.
