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

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 (NYSE: PFE  ) , 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. (NYSE: LLY  ) 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 (NYSE: FRX  ) . 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 (NYSE: JNJ  ) 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 (NASDAQ: PRAN  ) .

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. 


Read/Post Comments (8) | Recommend This Article (9)

Comments from our Foolish Readers

Help us keep this a respectfully Foolish area! This is a place for our readers to discuss, debate, and learn more about the Foolish investing topic you read about above. Help us keep it clean and safe. If you believe a comment is abusive or otherwise violates our Fool's Rules, please report it via the Report this Comment Report this Comment icon found on every comment.

  • Report this Comment On August 23, 2013, at 10:09 AM, funfundvierzig wrote:

    With a market cap of less than $200 million, Prana

    Biotechnology appears to be substantially under-priced given the probability of some significant success after more than a decade of promising research done on metallic interactions within the brain. If one or both Phase II tests for Huntington's and Alzhemer's yield favourable results, PRAN could conceivably soar skyward, doubling or tripling or better from its current price of circa 5.25.

    Merely the individual opinion of one retail investor with a long position of 13,000 PRAN shares...funfun..

  • Report this Comment On August 23, 2013, at 11:56 AM, usubanas wrote:

    Good title. After that, not so much. You could have mentioned lots of more promising treatments in development instead of the old Bapi and Sola. But I'll leave that to you for homework for your next 'corrected' version of this post.

    Regarding Prana, results in October 2013 are for Huntington's (not Alzheimer's), Alzheimer's results early next year.

  • Report this Comment On August 23, 2013, at 1:30 PM, gadfly1776 wrote:

    Hello fellow Americans,

    Alzheimer's is not a great medical mystery. It's cause has been well known for at least 30 years. What causes Alzheimer's and other dementias is a chronic energy deficit in the brain, due to insulin resistance, damaged brain-blood barrier, and inflammation in the brain caused by MSG-like chemicals, vaccinations, heavy metals, trans-fats, prescription drugs, air pollution etc. Energy deficit occurs over a period of 20 years or so before symptoms appear. Without enough glucose, your brain cannot make enough cholesterol and phospholipids to maintain myelin sheaths and synapses. As the cholesterol in the brain becomes depleted, the amyloid precursor protein is increasingly cleaved by beta secretase in the lipid rafts leaving beta amyloid as a marker. The greater the energy deficit, the more beta amyloid is produced. The solution is to provide the brain with an alternate energy source and to cut down on the inflammation from the above mentioned sources. Medium chain fatty acids, as from organic coconut oil work great. They are quickly metabolized in the liver to ketones which the brain and the rest of the body can then use for energy. One to two tablespoons 3 times daily works well. This stops the progression of the disease to a minimum. Most of my patients regain nearly normal function if started early enough. For prevention, use 1 tablespoonful twice daily.

  • Report this Comment On August 23, 2013, at 3:46 PM, Profbam wrote:

    The article, and also many of those trying to develop drugs, do not seem to understand Alzheimer's disease. The start is 10 or even 20 years before diagnosis. Typically a patient is brought in by family members because of memory issues. Clock test, digit span test, etc are given and a CAT scan ordered, which is found to show "diffuse cell loss consistent with AD." A billion neurons are already gone and never coming back. Only at autopsy are the plaques and tangles found to confirm the diagnosis. So here is the rub:

    If you could accurately diagnose AD 10 years before overt symptoms, do you have a drug that will prevent development of AD? If your test had 99% sensitivity and 95% specificity, will the side-effects allow use as a preventive? If not, you don't have a drug.

  • Report this Comment On August 23, 2013, at 4:40 PM, fifiviolus wrote:

    sir, i think that u and ur editors flipped the data readout dates for the AD and HD indications

    AD is in march 2014

    HD is in oct 2013

    this needs to b corrected if that is the case

    please check on that

    thx

  • Report this Comment On August 23, 2013, at 5:59 PM, fifiviolus wrote:

    and that mistake would b for PRAN data

  • Report this Comment On August 23, 2013, at 6:21 PM, Retaility wrote:

    Waiting on the sidelines for data on this one. Should be some meat on the bone if it lives up to expectations. Endpoint failure on the Alzheimer's study could tank this stock

  • Report this Comment On August 23, 2013, at 8:57 PM, TMFSunLion wrote:

    Thank you for pointing out the error in the Prana trial dates. A note has been sent to the editor to fix it.

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