The Past, Present, and Future of Alzheimer's Treatments

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Editor's note: A previous version of this article incorrectly stated that Eli Lilly's experimental drug solanezumab is a BACE inhibitor, and incorrectly noted the dates that Prana will release its results. It has been updated.

Alzheimer's disease, the most common form of dementia, is one of the greatest medical mysteries of our day. 5.2 million Americans are diagnosed with this debilitating disease, which is the sixth leading cause of death in the country. Alzheimer's disease usually occurs in patients over 65 years old, and is expected to affect one in every 85 people in the world by 2050 -- a startling figure considering that scientists still don't fully understand what causes the disease.

Those factors make the race to bring a real treatment for Alzheimer's disease a top priority for the biotech industry. Let's take a look at the past, present and future of these treatments to better understand the challenges that patients, scientists and biotech investors face.

Current treatments
The current market for Alzheimer's treatments generates roughly $20 billion in revenue annually, according to Deutsche Bank. However, these treatments only treat the main symptoms of Alzheimer's -- memory loss, confusion, and cognitive problems -- rather than the actual cause.

Aricept, developed by Eisai and Pfizer , is the most popular of these treatments. Aricept is a cholinesterase inhibitor which prevents the breakdown of acetylcholine, a chemical messenger needed for learning and memory. By keeping acetylcholine levels elevated, Alzheimer's symptoms can be held at bay for an average of six to twelve months in roughly half of the patients.

Aricept had peak sales of $2.4 billion in 2010, but have fallen dramatically over the past three years after its patent expiration. Today, generic Aricept is widely available from generics companies such as Actavis and Teva Pharmaceutical.

Namenda, which was first synthesized by Eli Lilly & Co. in 1968, is another common treatment for Alzheimer's disease. Namenda attempts to protect the brain's nerve cells against glutamate, a chemical messenger which is released in excess amounts by cells damaged by Alzheimer's disease and other neurological disorders. If glutamate binds to a patient's brain cells, it allows calcium to freely enter the cells, causing cell degeneration.

Namenda is currently manufactured by Forest Pharmaceuticals, a subsidiary of Forest Laboratories . Last quarter, sales of Namenda rose 7.9% year-on-year to $397.5 million, accounting for 48% of Forest Laboratories' top line. However, the patent for Namenda expires in 2015, which could send Forest over the edge of the cliff as generics enter the market.

The brain plaque problem
To treat the root cause of Alzheimer's, scientists are currently working on the theory of brain plaques -- extracellular deposits of beta amyloid in the gray matter of the brain. These brain plaques are believed to be neurotoxic and a major cause of the primary symptoms of dementia. The quest to clear away the plaque, however, has not been an easy one.

Pfizer, along with Johnson & Johnson and Elan Corporation (recently acquired by Perrigo Company), initially approached this problem with a plaque-clearing humanized monoclonal antibody known as bapineuzumab. Bapineuzumab attempts to use monoclonal antibodies to bind to beta amyloids directly to clear them individually. However, bapineuzumab was shown to be ineffective in patients with mild to moderate Alzheimer's disease. Development of an intravenous formulation of the drug was halted last August, and a Phase II subcutaneous formulation of the drug was discontinued in July.

Eli Lilly, has been working a a drug of its own called solanezumab. However, Lilly hit a major roadblock last year when solanezumab showed poor efficacy on advanced Alzheimer's patients in Phase III trials. Rather than give up as its peers have done, Lilly went back to the drawing board by focusing the treatment on mild Alzheimer's cases instead, on a larger group of 2,100 patients.

Lilly faces some tough competition going forward. Merck and AstraZeneca are also developing potential treatments that could compete with solanezumab if they produce successful results and Merck has already presented positive results for its Phase Ib study of its drug, MK-8931.

Smaller competitors at the gates
Big Pharma is not alone in its quest to uncover the elusive treatment for Alzheimer's. Last year, over 1,000 clinical trials were conducted to test various methods of treating the disease. Many of these trials were conducted by smaller, developmental stage companies, like Prana Biotechnology .

Prana's lead drug, PBT2, is a copper/zinc ionophore which was shown to restore cognition in animal models of Alzheimer's disease. The drug targets the zinc and copper ions that are necessary for the assembly of the beta amyloid deposits, diffusing them and effectively detoxifying them. PBT2 is currently in phase 2b clinical studies for Alzheimer's and [hase 2a clinical trials for Huntington's disease, a neurodegenerative genetic disorder. The full results from the Alzheimer's trial will be released next March, and the results of the Huntington's trial will be available in October.

Although Prana is a small fish in a sea of much larger competitors, its progress with PBT2 makes it one of the more important names to watch in the race to treat Alzheimer's.

A Foolish final thought
The number of Alzheimer's cases is forecast to triple by 2050 as the world's population ages. All of these biotech companies are focused on different methods of clearing out beta amyloid plaques, but the theory that reducing the plaques could treat or cure Alzheimer's disease is still unproven. However, scientists are steadily finding out that some treatments work better than others.

The monumental failure of bapineuzumab showed them that taking the monoclonal antibody approach -- a commonly used one in oncology treatments -- to clear out the plaque was ineffective. Lilly still believes that its treatment, solanezumab, could help clear beta amyloid plaques from the body, while Prana thinks that depriving the body of the essential components in the assembly process of beta amyloids could prevent plaques from forming.

For biotech investors, this is an exciting field to watch. If Lilly is successful at demonstrating that its treatment can treat milder cases of Alzheimer's, it could win back investors who had previously avoided the stock due to the looming expiration of Cymbalta, the antidepressant that accounts for roughly a fourth of its annual sales. However, investors should also keep an eye on Merck and AstraZeneca, which could beat Lilly in the race to release an approved BACE inhibitor treatment. Last but not least, we need to keep an eye on the small guys like Prana, which hold a lot of potential upside for investors with a stronger appetite for risk. 

The article The Past, Present, and Future of Alzheimer's Treatments originally appeared on

Leo Sun has no position in any stocks mentioned. The Motley Fool recommends Johnson & Johnson. The Motley Fool owns shares of Johnson & Johnson. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy. Is this post wrong? Click here. Think you can do better? Join us and write your own!

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