Bright Future For New Breed Of Alzheimer’s Drugs
Until this year, Alzheimer’s disease was a mystery to physicians and researches alike. Although it had become increasingly more common in the population, it had remained elusive in the laboratory. However, this year has seen an explosion in research findings regarding Alzheimer’s disease that has many companies geared up to find the first blockbuster treatment.
While some type of pharmaceutical treatment is on the market for most diseases, Alzheimer’s is not one of them. Pfizer is the only company with a drug approved by the FDA to treat Alzheimer’s disease. But while the drug, Aricept, temporarily relieves the symptoms, it does nothing to stop the progression of the disease.
The market for pharmaceutical treatments is wide open. The race is on to be the first to develop an effective drug to treat this increasingly prevalent disease.
Market Share: The sky is the limit
How big is the Alzheimer’s disease market? Today, 10% of persons over 65 have this disease, and it is seen in 50% of those over the age of 80. Currently, at least five to six million people in this country are affected by it, with a yearly health care cost of $80 to $90 billion. Also, the market is growing each year as the baby boomer generation ages.
The aforementioned drug being used to treat symptoms merely delays the inevitable. Yet the current drug cost to society is $600 million and is expected to reach well over $2 billion by the year 2003. The pharmaceutical industry is well aware of the market potential for an effective treatment of Alzheimer’s disease; many are starting up clinical trials given the recent scientific advances.
Understanding the disease?
Most likely, many people reading this article have a relative or know of someone with Alzheimer’s disease. According to clinicians, Alzheimer’s is a progressive degenerative disease of nerve cells in strategic locations in the brain, leading to memory loss, cognitive disabilities, and ultimately death. It is primarily seen in the older population; the specific cause is not known. However, researchers have recently made great inroads into deciphering its mystery.
It is now known that most Alzheimer’s patients have a buildup of plaque, known as beta-amyloid, in the brain. This plaque is a normal byproduct of nerve cells. In the normal brain, it is easily re-absorbed and is of no consequence.
However, in patients with Alzheimer’s disease, something happens to the normal disposal mechanisms, causing the plaque to build up in key areas of the brain. The plaque accumulates where memory, thinking and emotions are processed, entangling itself around individual nerve cells and ultimately strangling them. In addition, the excess plaque induces an inflammatory reaction in the brain, causing further damage to nerve cells. We do not know why this occurs, but recent discoveries may have the answer.
Latest discoveries
This year has seen the discovery of what may lead to the first wave of Alzheimer’s drugs within the next few years. In April, researchers at Harvard University discovered an enzyme that may be involved in the production of the plaque seen in the brain of Alzheimer’s patients. This enzyme, called gamma-secretase, was discovered in mice and is now known to play a crucial role in the making of amyloid.
In October of this year, scientists at Amgen reported the discovery of another enzyme, beta-secretase, crucial to the formation of plaque in the Alzheimer’s brain. It appears that both these enzymes, gamma- and beta-secretase, are necessary for amyloid plaque to form in the brains of genetically altered mice. What does this mean for humans? It could mean everything as treatment strategies are developed.
The drug industry’s tactical approach
With this new information in hand, the pharmaceutical industry has several targets to aim at and is in the process of creating drugs to take out each one. The first and most obvious targets are the enzymes beta- and gamma-secretase. Several companies have developed drugs to potentially stop these enzymes from working and thus eliminate the buildup of plaque seen in the brain of Alzheimer’s patients. These so-called secretase inhibitors have great promise and are just beginning to enter clinical trials.
The second target the pharmaceutical industry is aiming at is the inflammatory reaction caused by the buildup of amyloid plaque in the brain. This reaction is toxic to nerve cells in the brain. If drugs can be developed to stop or reduce this reaction, the progression of the disease can potentially be stopped or even reversed. Several companies are actively pursuing this line of research with drugs already on the market.
The last target is the individual nerve cells in the brain. If researchers can find a way to regenerate or repair brain nerve cells, they can go a long way toward curing many neurological diseases, including Alzheimer’s disease. The conventional thinking used to be that we are born with all the brain cells we will ever have. Well, this was proven to not be the case. It may be possible to generate new brain cells with the help of precursor stem cells, which we discussed in an earlier article on cloning. This already has been demonstrated in mice and is being explored in humans as the technology is made user friendly.
The companies doing the targeting
Eli Lilly [LLY>LLY], maker of the blockbuster depression drug Prozac, and Scios Corporation [SCIO>SCIO], a small biotechnology firm, have teamed up to develop several secretase inhibitors, which have the potential to inhibit the formation of amyloid plaque in Alzheimer’s patients. These compounds have shown great promise in the laboratory; human clinical trials are expected to start in the next several months. (Scios is also involved in the development of a drug to induce the growth of new blood vessels in the heart.)
Elan Corporation [ELN>ELN], an Irish pharmaceutical company, reported in July the results of a vaccine made from beta-amyloid. The company found that this vaccine significantly reduced the buildup of plaque in genetically altered mice and potentially could be used to prevent or treat Alzheimer’s disease. The vaccine was designed to stimulate the body’s own immune system to prevent or rid itself of the amyloid plaque. The side effects were minimal and the results so encouraging that the company expects to apply to the FDA to start human clinical trials by the end of this year. Elan has been trading in the $25 range with a 52-week high of 43 15/16.
By now, everyone has heard about the new arthritis blockbuster Celebrex, the baby of Pfizer [PFE>PFE] and Monsanto’s [MTC>MTC] G.D. Searle. Celebrex has easily outpaced Viagra as the most popular new drug around. It has a tremendous following among physicians because it can be used to treat the inflammation associated with arthritis with a lower incidence of ulcer problems than other drugs. I believe the best is yet to come with this drug, both from a health perspective and a pharmaceutical market perspective.
Population studies have clearly shown several other benefits of the drug class that includes Celebrex. These include a reduction in colon polyps and possibly colon cancer, as well as a 50% reduction in the risk of Alzheimer’s disease. By the very nature of its action, Celebrex, and drugs like it, inhibit the inflammatory process often seen in the brains of Alzheimer’s patients. Celebrex is currently in advanced human trials to see if the data is truly there for Alzheimer’s disease. If the data is confirmed, the market for Celebrex will be unlimited, enormously benefiting both Pfizer and Monsanto.
Not to be outdone, Merck’s [MRK>MRK] Cox-2 inhibitor Vioxx is also in the late stages of human trials to evaluate its value in the treatment of Alzheimer’s disease. The question is who will get there first.
Neotheraputics [NEOT>NEOT] recently presented data at a prestigious neurological meeting on their new drug Neotrofin for the treatment of Alzheimer’s disease. Neotrofin is a growth factor that can stimulate new nerve regeneration and potentially treat stroke, spinal cord injury, and brain disorders such as Alzheimer’s.
Neotheraputics’ early data with Alzheimer’s patients has shown the drug to have a positive effect on memory and emotional function. Advanced clinical trials are ongoing. Neotheraputics also has a pipeline of drugs to potentially treat other neurological disorders such as depression and migraine headaches, both large markets. The stock price has been trading in the $12 range, with a 52-week high of 16 1/4.
Aventis SA (merger of Rhone-Poulenc and Hoechst AG) has a drug in the pipeline called Viviq, which has shown exciting promise in the treatment of Alzheimer’s disease. Viviq has the ability to protect individual nerve cells in the brain by blocking harmful free radical compounds, which are byproducts of normal physiology. By exhibiting a protective effect in Alzheimer’s patients, it may be possible to stop the progression of the disease and improve mental function. Final clinical human trials are slated to start early next year.
Roche Holdings also has a drug in clinical trials that protects the nerve cells in patients with Alzheimer’s disease. Their drug, called Tempium, appears to have the ability to keep damaging free radical compounds from attacking nerve cells in the brain. Its protective effect is similar to Aventis SA’s Viviq, and it, too, is in the late stages of clinical trials.
Another benefit of estrogen?
Premarin, the most prescribed drug in the world, is an effective estrogen replacement in post-menopausal women. Its benefits to the heart and skeletal system in women are well documented. However, like many others, this old dog may be able to learn new tricks.
It has been observed in large population studies that women on Premarin have a lower incidence of Alzheimer’s disease. Premarin is believed to protect the brain from the plaque buildup so often seen in the brain of Alzheimer’s patients. Currently, there are several large-scale trials in advanced stages that could lead to a definitive answer. American Home Products [AHP>AHP] could greatly benefit from this data if positive and will have a tremendous jump on the competition.
The last word
I see the market for new drugs to treat Alzheimer’s disease exploding in the next one to three years in light of recent scientific developments. With the population aging, this relatively untapped market will be a pot of gold for the company that arrives on the scene first and with strength. If the data is supportive, there should be a rapid market expansion of already known drugs such as Monsanto’s Celebrex, Merck’s Vioxx and American Home Products’ Premarin into the Alzheimer’s field.