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Lilly And Sanofi CEOs Take Two Very Different R&D Paths In Alzheimer's Disease

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Alzheimer’s Disease (AD) R&D might be the most challenging therapeutic area that faces medicine today. It is known that AD is caused by the build-up of proteins into clusters that clog up nerve cells in the brain. These “plaques” break down nerve cells which, in turn, results in a decrease in the ability of these cells to function thereby leading to the familiar AD symptoms of memory loss and erosion of cognitive skills.

How these plaques form is a matter of scientific debate. One theory is that AD is caused by the build-up of the protein, beta-amyloid, and that if you can prevent deposition of this protein in the brain, you can slow plaque progression. Unfortunately, two compounds designed to do just that, Pfizer ’s bapineuzumab and Lilly’s solanezumab, failed in late stage clinical trials, thus casting doubt on this hypothesis. A second theory is that AD is caused by the build-up of another protein, known as tau, inside neurons where tau causes protein tangles. Interestingly, post-mortem samples of AD patients show that there is a correlation between tau protein tangles and the degree of AD severity.

What further complicates finding a cure for AD is that it is unclear how best to conduct clinical trials to determine the efficacy of a new experimental medicine. It is not known if a patient needs to be treated long before AD is fully apparent or if people need to be treated at the first signs of disease. Once the AD process starts, can it be halted or reversed? Should people with a perceived genetic predisposition to AD be treated to slow or prevent the onset of the disease? All of these questions need to be answered. However, to do this, long and expensive clinical trials are required as was done with bapineuzumab and solanezumab. Thus, the challenges that exist in AD go well beyond the normal R&D process of having a hypothesis and finding a compound safe and potent enough to test the hypothesis in patients. Unlike a disease like cancer where clinical trial protocols are well established, in AD even the clinical trial design is at an experimental stage.

Because of these challenges, last year I speculated that pharma companies might exit AD R&D.  Last week, Sanofi ’s CEO, Chris Viehbacher, did just that. As reported by Bloomberg ’s Drew Armstrong, Viebacher said the following:

“I think we have to do a lot more basic science work to understand what’s going on. We really, at best, partially understand the cause of the disease. It’s hard to come up with meaningful targets.”

One can’t blame Viehbacher for taking this position. After all, there are a lot of diseases where new and/or better treatments are needed, diseases whose pathology is better understood and where the chances for success are greater. My guess is that his shareholders will support his decision to make safer R&D bets. But, as the lifespan of the world’s population increases, so will cases of AD. Furthermore, the increased financial burden of this disease will have an enormous impact on healthcare budgets. The fact is that our best hope in bringing new AD medicines to market rests with the major pharmaceutical companies as they are the only ones with the necessary resources to be able to perform the key clinical trials that will ultimately yield a breakthrough. If Sanofi’s stance is mimicked by other companies, the chances of an AD breakthrough greatly diminish.

However, as Sanofi was stepping down last week, Lilly was stepping up. As reported by Jonathan Rockoff in the Wall Street Journal, Lilly has “double-downed” in its efforts, as indicated by Lilly VP, Dr. Dan Skovronsky:

“The most meaningful impact in Alzheimer’s might involve targeting multiple pathways and using combinations of drugs.”

Lilly’s plan is to go after AD by combining drugs that prevent beta-amyloid deposition and also tau protein tangles. To help them in doing this, Lilly has bought the rights to tau-measuring tests from Siemens . As Skovronsky explained:

“The whole field has been amyloid-centric, amyloid-driven. But we need more than that. That’s why we’re investing in tau."

There is no doubt that Lilly has taken a much bolder move in AD compared to Sanofi, and it’s a move that will be challenged by industry analysts. But Lilly has stepped up to the plate on a health issue that has major consequences for us all. I, for one, am very happy that they are making these important, but high risk, investments.