Controversy over High Dose Aricept

Contributed by: Dennis Fortier, President, Medical Care Corporation

 A consumer advocate group is calling for a ban on the 23mg Aricept dosage, which was approved by the FDA for more severe stages of Alzheimer's.

While Aricept is the mostly widely prescribed drug for the treatment of AD, it is most commonly prescribed in 5mg and 10mg doses.  Its efficacy in controlling symptoms is only moderate, but it has been on the market for more than a decade and has a solid safety profile.  The more recently approved, higher dosage of 23mg has been associated with a higher incidence of side effects and, according to the advocacy group Public Citizen, has no greater efficacy.  The primary side effects are nausea, vomiting, and agitation.

It is unclear whether the FDA will act on the petition to review the data and reverse the former approval for this dosage.  However, the most salient point for treating physicians to understand is that, regardless of the dosage, cholinesterase inhibitors like Aricept yield the most clinical benefit when prescribed as poly-therapy along with Namenda.  The data supporting this clinical approach are clear and compelling.

Negative Press for Alzheimer's Drug

Contributed by: Dennis Fortier, President, Medical Care Corporation

Reporting the news is a business.  This is why stories with market appeal, even if they have little news value, or may even be misleading, sometimes get broad coverage.  I am sure most editors sincerely want to present the most important stories and filter out the trivial items, but there is always a tendency to promote a compelling headline.

Over the last two days, you may have seen headlines that Namenda, one of the approved Alzheimer's drugs on the US market, does not work for patients with mild AD.  These headlines are based on an article published in this week's online issue of the Archives of Neurology.  In this study, researchers at the University of Southern California, performed no new research on the drug, but reviewed data from three other published studies, and concluded that Namenda is not beneficial for patients with mild AD.

I am not sure why this has been so broadly reported in the press, and I would like to emphasize two points:

1) Namenda is not approved for use in mild stage patients, only for moderate and severe stage patients.  This study reached exactly the same conclusions as the FDA reached when they approved the claims for the drug.  No news there.

2) Namenda has been shown to benefit early stage patients when combined with other approved Alzheimer's medications such as Aricept and Exelon.  To craft an interesting headline based on only half the story is fairly disingenuous.

To be fair to the press,  there may be value in reporting that many physicians prescribe Namenda for early stage Alzheimer's and, if prescribed alone (without one of the other drugs shown to boost efficacy), then the effects are probably minimal for most patients.  In that case, a legitimate framing for the story would convey that the drug is not being used properly, as opposed to conveying that the drug is not effective.

I have no ties to the pharmaceutical industry and I don't wish to sell false hope to the public about drug efficacy against Alzheimer's disease.  However, some people respond better than others to existing treatments, and every one deserves the opportunity to find out how treatment will affect them.  It is a shame to discourage physicians and patients from seeking potentially beneficial therapy just so you can sell more press with an eye-grabbing headline.

Are Alzheimer's Drugs Better than Previously Thought?

Contributed by: Dennis Fortier, President, Medical Care Corporation
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A very big story about Alzheimer's treatment is unfolding in Europe. This story is big from a news coverage point of view and also from the perspective of real world impact. I am referring to the story about the National Institute for Health and Clinical Excellence (NICE) in the U.K. that has reviewed ongoing science and reversed their earlier stance on Alzheimer's drug efficacy.

Background
In 2006 and 2007, NICE recommended against National Health Services paying for cholinesterase inhibitors (the primary class of Alzheimer's drugs) for patients with mild to moderate Alzheimer's disease. They based this recommendation on a financial analysis suggesting that the economic benefits of treating AD with those drugs (Aricept, Exelon, and Razadyne) in its mild and moderate stages did not outweigh the costs of the treatment.

Naturally, that recommendation sparked lots of debate, including an argument that most experts considered very legitimate. The argument was that "average treatment effect" is merely a composite derived from some patients who responded well to treatment and others who did not. Since it was clear that treatment has meaningful benefits for some patients, and no one can predict which patients will respond, then everyone deserves the chance to find out.

New Position
Now, based on an ongoing review of emerging data from new studies, NICE is planning to revise that recommendation. This is great news for the patients afflicted with AD who have not yet progressed to the severe dementia stage. It is also important for the effect this move will have on the global conversation and the public perception of treatment efficacy.

Optimal Treatment
The one point I think needs to be added to this story is that, the drug class in question is only one part of the robust treatment approach we know to be most effective in delaying the progression of Alzheimer's disease. Optimal treatment includes poly-therapy (cholinesterase inhibitor plus Namenda), a balanced diet, physical exercise, and tight control of other conditions such as diabetes and hypertension.
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A better understanding and more awareness of Alzheimer's related issues can impact personal health decisions and generate significant impact across a population of aging individuals. Please use the share buttons below to spread this educational message as widely as possible.

Alzheimer's Treatment: Combo-Therapy is Best

Contributed by: Dennis Fortier, President, Medical Care Corporation
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A new study presented at the 14th Congress of the European Federation of Neurological Societies (EFNS) strongly supports earlier findings about treatment efficacy of combination therapy. The research showed that, when treating Alzheimer's disease, a combination of a cholinesterase inhibitor like Aricept plus Namenda is significantly better than mono-therapy with a cholinesterase inhibitor only.

In this study of more than 400 patients with moderate to severe Alzheimer's disease, significant improvements in patients receiving combined therapy were noted in cognition, function, behavior, global outcome, and care dependency. These are robust findings that might begin to change nihilistic attitudes toward Alzheimer's treatment.

The most optimistic view of treatment efficacy comes not only from studies like this, showing the benefits of combo-therapy, but from a more robust approach. To maximize treatment effect, we need to intervene earlier in the disease process so that patients can start therapy before massive neuron death and synapse loss occurs. Additionally, we need to augment the benefits of drug treatment with a balanced diet, physical activity, and proper control of other co-morbid conditions such as diabetes ad hypertension. Most probably, staying intellectually active and socially engaged is also beneficial.

Given the generally defeatist tone of most press about Alzheimer's treatment, I am happy to see the occasional positive press about our ability to combat this disease. We have a long way to go but the facts are more comforting than most headlines suggest.
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A better understanding and more awareness of Alzheimer's related issues can impact personal health decisions and generate significant impact across a population of aging individuals. Please use the share buttons below to spread this educational message as widely as possible.

Are TV Advertisements for Aricept Misleading?

Contributed by: Dennis Fortier, President, Medical Care Corporation
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According to the FDA, they are.

Aricept is the most commonly prescribed treatment for Alzheimer's disease. It is indicated for treatment of mild to moderate dementia of the Alzheimer's type and data from FDA clinical trials suggests that it is more effective in relieving symptoms than in delaying the underlying disease.

However, recent television advertisements sponsored by Eisai (manufacturer of the drug) and Pfizer (US distributor of the drug) depict adults first meeting with a doctor, accompanied by an apparent caregiver, and then later engaged in daily activities such as gardening and caring for pets. In the opinion of the FDA, these ads suggest a level of improvement that is not supported by clinical data. The ads are currently suspended while the companies respond to the FDA's complaint.

Whatever the outcome, it is important to understand the treatment efficacy of cholinesterase inhibitors (the class of drugs to which Aricept belongs). Data from the FDA clinical trials suggest a symptomatic benefit and ongoing analysis of those data indicate a small but discernible disease delaying effect for some patients, especially those who begin treatment at an early stage of the disease. Importantly, it is now well established that a cholinesterase inhibitor combined with Namenda (a partial glutamate antagonist) yields the most benefit over the longest treatment period.

Aricept to be Available in New Formulations?

Contributed by: Dennis Fortier, President, Medical Care Corporation
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Eisai, Inc., makers of the most widely prescribed Alzheimer's medication (Aricept), released a status update today on two studies they have sponsored. The indications are that they expect to bring two new formulations of Aricept to the market in the future.

First, they have concluded a successful review of phase III data on a sustained release capsule that could improve clinical outcomes by mediating the dose of the drug in the bloodstream. The company announced an intention to file and NDA (New Drug Application) with the FDA by end of summer 2009.

Eisai also announced that they are studying a transdermal patch formulation at locations in Japan and the USA. Their expectation is that an NDA for this formulation might be filed within the next 12 months.

The FDA pipeline for new Alzheimer's treatments is quite full but it is encouraging to see that those drugs already approved are also being optimized through ongoing research and development.

More News on the Relationship Between Alzheimer's and Depression

Contributed by: Dennis Fortier, President, Medical Care Corporation
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A study published in the June 16 issue of Neurology, the journal of the National Academy of Neurology, suggests that people with memory loss who are also depressed have a greater likelihood of getting Alzheimer's disease (AD).

In a three year study of 756 subjects aged 55 to 91, those diagnosed with depression and memory loss developed AD at a higher rate than those with memory loss and no depression.

The study also had some good news about Aricept, a cholinesterase inhibitor commonly used to treat AD. Among a group of subjects with both memory loss and depression, 11% of those given Aricept developed AD during the study while 25% of those not given Aricept developed AD.

This finding suggests that Aricept may have slowed the progression of Alzheimer's pathology and prolonged high quality of life. This bodes well for our ongoing ability to treat AD in a more effective manner.

Limited Availability of AD Drugs in the UK

Contributed by: Dennis Fortier, President, Medical Care Corporation
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The National Institute for Health and Clinical Excellence (NICE) in the UK has ruled again that paying for cholinesterase inhibitors (drugs including Aricept, Exelon, and Razadyne) is not a cost-effective use of NHS funds. As such, these drugs are essentially unavailable to patients with mild Alzheimer's disease in the UK.

In 2005, NICE made the initial ruling that denied reimbursement for these drugs for mild and moderate stage Alzheimer's patients. After public outcry, the ruling was amended to allow treatment for moderate but not mild stage disease. With a rightly unsatisfied public, the manufacturers of these drugs pushed for a judicial review which has yielded this latest news of NICE standing firm on its past decision.

It is speculated that, with the judicial process complete, NICE will begin a new review of its policy incorporating latest clinical data that may lead to a more aggressive treatment policy going forward.

Dimebon Trials

Contributed by: Dennis Fortier, President, Medical Care Corporation
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New potential treatments for Alzheimer's disease and the progress of their FDA trials are high interest news stories with lots of coverage. Two Dimebon studies are currently in progress or being planned. For those interested in learning more about how to participate in one of these studies, detail links are below.

The selection criteria and additional details for the CONNECTION study are published at the Medivation website.

Information about the forthcoming CONCERT study, a combination therapy approach including Aricept, is available at a special "CONCERT study" website where information will be published as it becomes available.

AD Treatment Perspective #5

Contributed by: Dennis Fortier, President, Medical Care Corporation
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Recent evidence from Harvard University and Massachusetts General Hospital shows that combination therapy of cholinesterase inhibition (Aricept, Exelon or Razadyne) plus Namenda is most effective in slowing disease progression. These combinations can preserve ADL's (Activities of Daily Living) and delay nursing home placement by several years in some patients.