Optimism About New Alzheimer's Drugs

Contributed by: Dennis Fortier, President, Medical Care Corporation

A few weeks ago, we wrote about the glimmering ray of hope that had emanated from bad news about potential new Alzheimer's treatments.

Both Bapineuzumab and Solanezumab, the two most progressed new drugs in the development pipeline, had both failed the final stage of their respective clinical trials, and would not be approved by the FDA. However, there was some evidence, and much speculation, that both drugs had shown signs of efficacy in secondary data analyses.

Now, as presented at the American Neurological Association's 2012 annual meeting earlier this week, those secondary analyses have been verified and a newfound optimism has swept the field.

Of course, drug approvals require a massive investment of time and money, and drug companies must always weigh the costs of completing that high risk process, against the benefits they might capture during the few remaining years of the drug's patent life, once the process is completed and the drug is commercialized.

Readers might be surprised to learn that drug companies sometimes abandon effective drugs, if the approval process takes too long and the viable (patent protected) period for recouping their investment is too short. This is the decision that Eli Lilly (Solanezumab) and Pfizer (Bapineuzumab) must now face as they consider the time and cost of next steps to bring these drugs to market.

At this point, there are two encouraging signs that each company might push forward and lobby the FDA for an efficient path to near-term approval.  One is that the Federal government, under the National Alzheimer's Prevention Act, is committed to identifying new treatments for this disease.  The other, is that the Wall Street analysts, ever pessimistic about success of new AD drugs, have pushed Lilly's stock price upwards in the wake of this new information.

The Uncertain Future of Alzheimer's Research

Contributed by: Dennis Fortier, President, Medical Care Corporation
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Is this a crisis?  Two news items with similar themes, springing from disparate sides of the research funding equation, have been in the press this week.

First, I noted that the CEO of Eli Lilly, making a keynote address at The Economist's 2011 Pharma Summit, shared his strong view that current regulatory environment cannot sustain ongoing investment toward much needed innovation.  He made these comments specifically in regard to the neuroscience field, where the diseases are complex, developing new treatments costly, and economic returns uncertain.

His unspoken message was that major R&D investments from big pharma may not be sustained, even as the aging of the population increases the need for better treatments of Alzheimer's disease and other age-related conditions.

Secondly, Reuters has reported the view from academia that prospects for future investment in the neuroscience field will be bleak without new incentives to encourage such spending.  An excellent article summarizing the situation suggested patent law and the regulatory pathway as two areas where governments can cooperate with industry, to improve prospects for a return on new investment.

This is something to think about.  For sure, the need for better AD treatments is dire and will only intensify in the coming years and decades.  At the same time, profit driven pharmaceutical companies must strategically allocate their investment funds into areas that optimize a return.

Remember, there is no moral obligation for any corporation to perform "in the interest of humanity".  To the contrary, corporations have a legal obligation to perform "in the interest of their shareholders", which is to optimize economic returns.  Sometimes, helping humanity translates into profits, but the correlation is far from perfect.

Going forward, the best and most immediate solutions will likely come from a well orchestrated effort between private economic interests, academic resources, and prudent public policy that reduces barriers and provides the right motivation to invest.

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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 button below to spread this educational message as widely as possible.

What Next for PET Imaging and Alzheimer's Diagnosis?

Contributed by: Dennis Fortier, President, Medical Care Corporation
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Last week we noted here that Mayo Clinic had named certain bio-markers, specifically those agents that bind to amyloid plaques in the brain and become visible with a PET scan, as the most important medical innovation of the coming year.

Such bio-markers may help diagnose Alzheimer's disease with more certainty than current methods. However, many experts correctly point out that, down the road, cheaper and more practical tests based on blood or cerebral spinal fluid samples, might offer equal benefits in a more pragmatic approach. In fact, changing protein levels in the blood and spinal fluid are likely, according to current theories, to show changes prior to plaque formation in the brain and therefore, might offer even earlier diagnosis than PET scans.

Interestingly, Eli Lilly announced yesterday that they are acquiring Avid Radio Pharmaceuticals, the maker of the PET tracer agent that is likely to be the first to gain FDA approval in early 2011. Given an acquisition price of up to $800 million (depending on achievement of certain milestones), for a company with no sales, it is safe to say that big pharma is sold on the value of diagnosing Alzheimer's disease with PET imaging.

The benefits of using bio-markers and PET imaging to diagnose AD, to detect changes in the brain during research, and to evaluate the effect of drugs in clinical trial, are all positive steps in our collective battle to reign in this terrible disease. But I am looking forward to even bigger steps and better solutions that seem to be following closely behind this exciting advance.

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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 button below to spread this educational message as widely as possible.

New Target For Alzheimer's Drug

Contributed by: Dennis Fortier, President, Medical Care Corporation
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This is an exciting story but needs to be embraced with proper expectations. The New York Times is reporting on research scheduled to publish tomorrow in Nature, that a promising new target has been identified for treating Alzheimer's disease.

The target is a protein that activates the role of gamma secretase in producing beta amyloid in the brain. Following the recent failure of Eli Lilly's phase III drug that inhibited gamma secretase, and the ensuing round of questions that the failure spawned about the validity of the amyloid hypothesis, this is fantastic news.

This finding points to a potential refinement of current thinking. It is clear that gamma secretase has multiple roles, some of which are neuro-protective and others which lead to overproduction of beta amyloid. As a treatment hypothesis, we are aiming to reduce the production of beta amyloid but inhibiting gamma secretase is apparently too crude of an approach. It seems as though the downside of inhibiting gamma secretase is greater than the upside, and two drugs based on that approach, have previously failed to show clinical benefits.

With the discovery of this new protein, it is suggested that we might be able to turn off the harmful activities of gamma secretase while allowing its beneficial activities to continue. This portends great hope.

One word of caution, to which I alluded in the opening. This science is a long way from being validated which is only the first step in a long FDA process to commercialization. If this discovery eventually turns out to be part of an effective treatment, that treatment is still many years from commercial availability.

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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 Disease: Status of the Amyloid Hypothesis

Contributed by: Dennis Fortier, President, Medical Care Corporation

For some time now, the leading explanation of Alzheimer's disease has been an abnormal accumulation of beta-amyloid in the brain, which leads to cell death and impaired mental function.

While the amyloid hypothesis has been the leading explanation, it has not been universally accepted and is only one of several possible explanations of Alzheimer's pathology. Each time results are released from an FDA trial, researchers scramble to reconcile the results with what is known about treatment targets and the underlying mechanisms of disease progression.

Yesterday's announcement by Eli Lilly that they were canceling development of an agent formulate on the the amyloid hypothesis has reignited discussions about the cause of Alzheimer's disease. A very thorough summary, with cogent, expert commentary from both supporters and detractors, was published today by Bloomberg. This short article provides a balanced view of where the research community stands on the amyloid hypothesis.
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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 Drug Fails Phase III Trial

Contributed by: Dennis Fortier, President, Medical Care Corporation
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One of Eli Lilly's late-stage Alzheimer's drugs, the gamma-secretase inhibitor Semagacestat, has failed its Phase III FDA trial and the company has halted its development. This announcement today was somewhat expected by the research community as other gamma-secretase inhibitors, namely Flurizan (Myriad Genetics), had also been deemed ineffective in a large trial.

While this is disappointing news, the overall trend of scientific progress in the field of Alzheimer's is clearly positive. New guidelines have been proposed that will facilitate earlier intervention and better treatment results. New diagnostic tests are showing greater accuracy and bode well for more certainty in clinical practice. And perhaps most importantly, the pipeline of treatments under development is full of promising agents.

An updated summary of the current FDA pipeline for Alzheimer's treatments will be posted here later in the week.

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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 button below to spread this educational message as widely as possible.

Alzheimer's Drug Development by Eli Lilly

Contributed by: Dennis Fortier, President, Medical Care Corporation
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There seems to be a bit of confusion about the various drug trials currently underway by Eli Lilly. Here is a brief summary of their activity:

The IDENTITY trials are enrolling patients aged 55+ in over 30 countries including the USA. The compound in these studies is a gamma-secretase inhibitor that is hypothesized to reduce the accumulation of amyloid plaques in the brain.

The more recently announced EXPEDITION trials are enrolling patients aged 55+ in 16 countries including the USA. These studies are measuring the potential effects of an anti-amyloid monoclonal antibody (Solanezumab) delivered via intravenous infusion.

More details about each trial including how to inquire about enrolling can be found in this announcement from Eli Lilly.

Solanezumab – Another monoclonal antibody reaches Phase III

Contributed by: David Geldmacher, M.D., Medical Director of the Memory Disorders Clinic at the University of Virginia.
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On May 21, Eli Lilly and Co. announced that a Phase III Trial of their agent solanezumab, also known as LY2062430, would begin enrollment.

In Lilly’s Phase III program, a total of 2000 patients with mild to moderate AD are expected to receive either a 400 mg infusion of solanezumab or a placebo once every four weeks. Each research volunteer will participate over about 19 months. The overall trial is anticipated to be completed in mid 2012.

On first pass, this agent would appear to be similar to bapineuzumab which is already in Phase III trials being carried out by Elan and Wyeth. There are molecular differences between the two monoclonal antibody lines, which suggest that solanezumab acts primarily outside the brain to sequester soluble amyloid beta peptide in the peripheral circulation. If true, this would predict a lower risk for toxic events in the brain, like the vasogenic edema (brain swelling) reported in Elan’s Phase II trials.

On the other hand, a site of action outside the central nervous system might mean lower overall potency. Given the small absolute effects seen with bapineuzumab in its Phase II trial, lower potency would not bode well for solanezumab’s effectiveness. Of course, all anti-amyloid immnunotherapies depend a great deal on the validity of the amyloid hypothesis.

At a practical level, participants in the solanezumab trial will receive infusions every four weeks instead of the quarterly regimen for bapineuzumab. This will triple the risk for infusion related complications, and places a higher burden on patients. If approved under their current regimens, costs of drug administration would also likely favor the agent requiring the fewest number of infusions. However, a dramatically greater effectiveness would go a long way to off-setting increased treatment costs.