Alzheimer's drug results disappointing, but spin varies

Those looking for hope for Alzheimer's treatment won't get much from the latest clinical trial results from an experimental drug by Eli Lilly & Co.

The drug failed to slow cognitive decline in a trial of about 1,000 Alzheimer's patients. It failed to meet the primary endpoints selected in advance for the trial.

But Lilly claimed a modest -- very modest -- success when the results were combined with another clinical trial of the drug,  solanezumab . Those given the drug exhibited a statistically significant effect in slowing cognitive decline, in those with mild to moderate symptoms. It says this secondary analysis was "pre-specified", apparently meaning this wasn't a retroactive attempt to find effectiveness.


I know. Since there's no effective treatment now for Alzheimer's, even extremely modest results are better than nothing. But it's very easy to find evidence of effectiveness when you're looking for it. Verifying that the pattern is real is much harder.

And since Lilly says the evidence supports the amyloid hypothesis, that long-term build-up of these tangled proteins causes Alzheimer's, the drug would need to be taken for years to produce any potential benefit, presumably by those in the first stages of disease with only mild to moderate symptoms.

While the benefits are uncertain, there's no doubt the drug will be expensive. Lilly has to recoup its massive investment in research and development, including the large clinical trials. So while this drug may -- I repeat may -- represent progress, it's very modest progress indeed. It's not a breakthrough by any means.

Differing takes

It's instructive to compare the coverage of the Lilly trial in different media outlets. Outlets knowledgeable about the subject were not impressed. MIT's Technology Review said: " Another Bust for Alzheimer's Drugs ".

Derek Lowe, a medicinal chemist, was also unimpressed , although slightly more diplomatic, on his blog "In the Pipeline":

"Now, this news - what you've just read above - actually is sending Lilly's stock up as I write this, which tells you how beaten-down Eli Lilly investors are, or how beaten-down investors in Alzheimer's therapies are. Or both. The headlines are all about how the drug missed in these trials, but that the company sees some hope. But man, is it ever a faint one."

Lowe noted that the company talked about showing slowing in cognitive decline, but didn't make that claim in functional results:

"If I'm interpreting this right, that means that there was a trend towards efficacy in tests like remembering words and lists of numbers, but not a trend when it came to actually performing better in real-life circumstances. Am I seeing this correctly? Lilly will be presenting more data in October, and we'll know more then. But I'm not getting an optimistic feeling from all this."

Mass media outlets, which are less scientifically sophisticated, were more enthusiastic.

" Lilly Alzheimer's drug trial yields promising sign ," said a story in a newspaper based in Indianapolis, Lilly's hometown.

" Treatment shows promise to slow Alzheimer's progression " said USA Today.

" Lilly Alzheimer's drug trial yields promising sign ," the Associated Press headlined its story.

To be sure (the obligatory phrase of many journalists), solanezumab may yet show more impressive efficiency. At least that's what Decision Resources , which describes itself as "one of the world’s leading research and advisory firms for pharmaceutical and healthcare issues," said in March.

Decision Resources said that, "based on clinical data and the opinions of interviewed thought leaders, Eli Lilly’s anti-beta-amyloid therapy solanezumab will earn Decision Resources’ proprietary clinical gold standard status for the treatment of mild to moderate Alzheimer’s disease in 2015, following its launch for the indication beginning in 2014."

The press release indicates what we need to keep in mind about the highly uncertain process of drug development: Even "thought leaders" can get it wrong.

And on that note, let's keep in mind that the amyloid hypothesis itself may well be wrong. If it wrong, then companies developing drug based on that hypothesis may well be throwing away their money and time.

A Salk Institute research team  including Dave Schubert and Marguerite Prior followed a more pragmatic path. They screened drug candidates for effectiveness in mouse models, relying on cognitive and functional signs, not on any hypothosis of how Alzheimer's originates. They found a drug candidate that prevents memory loss and reduces the brain degeneration associated with Alzheimer's.

But taking that drug to the clinic takes money and a corporate sponsor. After the latest less-than-stellar results, Big Pharma may turn shy of this disease.

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