Unacknowledged in the public dialog surrounding Alzhemed's failure is the virtual certainty that trials of other anti-amyloid strategies that remain hopeful will exclude Alzhemed users.

The desperation of the disease can drive families and carers to make irrational choices. But, Alzhemed "nutraceutical" users, Caveat Emptor: You may unintentionally deny yourselves access to trials of immunotherapies and/or secretase modulators that, unlike Alzhemed/tramiprosate, continue to hold promise for slowing cognitive decline.

View all comments by Samuel Gandy

The decision to market tramiprosate as a supplement is surprising news. It does not speak well of nutraceuticals as a refuge for drugs that fail in clinical trials. From my perspective, it would be okay to fail in a clinical trial if they had compelling biomarker data from humans showing that the drug can really move a target, and established the dosing required to do it. The hippocampal volume data looks promising, but needs its own supplement, perhaps with a CSF biomarker cocktail that includes tau given the report from Avila (see ARF related news story) that the compound can promote tau aggregation. One problem with people self-dosing a nutraceutical is the typical lack of information about the dose required to move an endpoint. And at least they have a dose response on the hippocampal volume, and apparently at least some patients clamoring for more because they thought that it helped them.

The great value with nutraceuticals would be for prevention. There, the clinical endpoint is hard to come by, especially in...  Read more

The decision to market tramiprosate as a supplement is surprising news. It does not speak well of nutraceuticals as a refuge for drugs that fail in clinical trials. From my perspective, it would be okay to fail in a clinical trial if they had compelling biomarker data from humans showing that the drug can really move a target, and established the dosing required to do it. The hippocampal volume data looks promising, but needs its own supplement, perhaps with a CSF biomarker cocktail that includes tau given the report from Avila (see ARF related news story) that the compound can promote tau aggregation. One problem with people self-dosing a nutraceutical is the typical lack of information about the dose required to move an endpoint. And at least they have a dose response on the hippocampal volume, and apparently at least some patients clamoring for more because they thought that it helped them.

The great value with nutraceuticals would be for prevention. There, the clinical endpoint is hard to come by, especially in diseases with long and very expensive trials. Also, insurance may not pay without a diagnosis. So I think you could argue that tramiprosate might work for prevention but not with established AD. In the absence of a convincing clinical trial, tramiprosate needs solid data to show that it moves a panel of biomarkers relevant to pathogenesis. I have been unable to understand how tramiprosate could get into the brain as a charged compound, and not understanding makes me suspicious.

My Alzheimer Center colleagues pointed out that tramiprosate is a modification of taurine. Taurine is a major component of the "energy drink" Red Bull, which is also loaded with caffeine. At SfN, Gary Arendash talked at a news conference about how caffeine is treating his transgenics and is blocking both β- and γ-secretase. So it is beginning to sound like we'll be seeing something like a cross between Red Bull and Rock Star (another energy drink containing ginkgo extract and caffeine) for seniors, Perhaps we should have a naming contest? Combining the last too initials in the cross would tempting, but so far I like Senior Bull.

View all comments by Gregory Cole

Reader advisory: These comments may appeal only to readers of a certain age, who remember black-and-white TV and Richard Nixon.

Sean Silcoff, a reporter for Neurochem’s hometown paper, The Toronto Financial Post, describes the Alzhemed story as playing out like the Monty Python dead parrot sketch, a discussion between a pet store owner and a customer over whether a dead parrot is dead or just resting or stunned.

Neurochem had been going around and around about the vital status of its North American trial, and landed its most recent stunner on November 8, 2007, the essence of which is that since there is no evidence for tramiprosate’s efficacy by any conventional scientific standard, Neurochem will market homotaurine—the amino acid formerly known as the drug tramiprosate—as a food supplement or...  Read more

Reader advisory: These comments may appeal only to readers of a certain age, who remember black-and-white TV and Richard Nixon.

Sean Silcoff, a reporter for Neurochem’s hometown paper, The Toronto Financial Post, describes the Alzhemed story as playing out like the Monty Python dead parrot sketch, a discussion between a pet store owner and a customer over whether a dead parrot is dead or just resting or stunned.

Neurochem had been going around and around about the vital status of its North American trial, and landed its most recent stunner on November 8, 2007, the essence of which is that since there is no evidence for tramiprosate’s efficacy by any conventional scientific standard, Neurochem will market homotaurine—the amino acid formerly known as the drug tramiprosate—as a food supplement or nutraceutical so that people with Alzheimer disease can buy it over-the-counter and not be deprived of the drug’s perceived potential benefits that the company touted in prior news releases and presentations.

This may be great news to some, “but wait, there’s more!” as Ron Popeil, the consummate TV purveyor of Veg-O-Matics, might say. According to the Financial Post, Neurochem expects to “scare up US $1 billion-plus sales” selling this nutraceutical and will use the proceeds to develop an effective AD drug, presumably one minimally effective enough that the FDA could actually approve it. In the meantime, people with or without AD can soon take tramiprosate thinking that it will both help them directly and also help fund Neurochem to develop effective future drugs.

One such Neurochem gleam-in-the-eye is the previously unheard-of NRM-8499, said to be a pro-drug of the very “food supplement” they will be selling—inevitably—on their TV infomercials. Neurochem states that NRM-8499 is five times more potent than their “Alzhemed” brand of homotaurine. (This of course begs the question why consumers shouldn’t just buy five times more of the nutraceutical than they would have bought of the prescription drug had it been demonstrated effective). The sales message—to be voiced probably by Hollywood and medical celebrities—could be, “Help Neurochem fight AD as you help yourself.” A Beverly Hills celebrity statistician could make an appearance here, too, because statistical modeling is so much a part of the Alzhemed story.

While they are at it, Neurochem could go further and tithe a portion of their proceeds to the Alzheimer’s Association, gaining a hefty tax credit and stating on each bottle of the Alzhemed brand of homotaurine, “all proceeds to Alzheimer’s charity.”

Even as the company announces that tramiprosate is not worth pursuing as an ethical pharmaceutical product, it continues to imply that there is efficacy to be found somewhere deep within the North American trial data. Seven months after they knew their results, they still speak of “promising results from preliminary post-hoc analysis,” “descriptive data” showing “numerical differences in favor of tramiprosate on the primary clinical endpoints,” “descriptive data also shows…differences between groups on the primary disease modification endpoint of change in the volume of the hippocampus,” or, to further obfuscate, “preliminary post-hoc analysis…that allowed adjustment for potential confounding factors showed a dose-dependent reduction in hippocampal atrophy in patients treated with tramiprosate.” Never mind inferential statistics; facts about efficacy matter less now than they had before for the marketers of a food supplement.

And now for something completely different…(as I am trying to “always look on the bright side....”): Having acknowledged—not by its press spin but by its business actions—that the North American trial did not show efficacy and that the company could not withstand the risks of its European trial, Neurochem might now just put their bird to rest. It should post the North American trials database, statistical analyses, data files, and clinical study report on their website for others to review and analyze. They cannot get FDA approval and by law cannot make specific AD health claims for a food supplement. Any manufacturer can make homotaurine or conceivably extract it from one or another species of algae, so they no longer have a proprietary need to hide the data. Posting the data would provide the best and most transparent support for their press releases. Consumers will be able to examine directly the efficacy evidence and judge for themselves.

Open access to the database and statistical models would allow clarification of the alleged methodological problems that Neurochem enumerates but doesn’t document (e.g., site variability, diagnostic uncertainty, confounding, and metrical issues). It may even allow other methodologists—using other Veg-O-Matics—to find things that may have eluded the Neurochem experts. Academics and advisors to companies and the NIH would learn more about AD clinical trials methods, avoid the repetition of mistakes that might be dooming otherwise effective drugs, and improve future trials methods. This, in turn, might help us to find effective drugs for AD sooner by improving the designs of trials and serve the common good. Of course, other companies and the NIA ADCS should post their clinical trials data, as well, and may do so if Neurochem sets the example. Finally, posting these data and reports would not undermine the publication of a primary paper in any major journal.

I leave it to others to explain why such a modest proposal for companies to share their data from negative trials so that others can benefit would be dead on arrival.

Disclosure: See 14 September 2007 comment.

View all comments by Lon Schneider