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Rethinking Alzheimer's


By taking a new tack in fighting the disease, a tiny Singapore startup may have the jump on Big Pharma

Take a Scottish scientist and a Singapore investor who met because their sons were schoolmates. Add in the accidental discovery that a 100-year-old malaria drug can repair damaged brains. The result is one of the few bright spots amid a slew of notable failures in Alzheimer's drug development.

TauRx Therapeutics, a private company based in Singapore, just reported that its drug Rember reduced mental decline by 81% over 12 months in a small phase II trial. The results have yet to be published and need to be confirmed by a larger trial. But so far, Rember has outperformed high-profile Alzheimer's drugs made by far larger companies. And it works by going after a completely different target.

Virtually every major pharmaceutical and biotech company is trying to develop a drug that can reverse or delay Alzheimer's, the biggest unmet medical need out there. Pfizer's Aricept and three other drugs now in use can only alleviate symptoms for a few months. Given that 26 million people worldwide have Alzheimer's, and 106 million could be afflicted by 2050, any treatment that alters the course of the disease would quickly become a multi-billion-dollar drug.

To date, most Alzheimer's researchers have pursued compounds that would clear out toxic clumps of a protein called amyloid that clog the brains of Alzheimer's victims. One amyloid drug after another has failed in trials, however. The most recent disappointment: an antibody developed by Wyeth (WYE) and Elan Pharmaceuticals that some analysts predicted would bring in $9 billion in yearly sales. On July 29 the two companies released mediocre trial results. The next day Wyeth's stock dropped 11.8% and Elan's 40%.

A month earlier, Myriad Genetics (MYGN) announced that its anti-amyloid drug, Flurizan, failed to show efficacy, and Myriad pulled the plug. And a year ago another once-promising amyloid drug, Alzhemed from Bellus Health (BLUS), was also abandoned after failing a trial.

Against that background, Rember looks pretty good. Dr. Claude Wischik, at the University of Aberdeen in Scotland, rejects amyloid as a cause of Alzheimer's. He has long studied another protein, Tau, which masses into tangles in diseased brains. In 1988 he tried to dye these tangles in a test tube with an old malaria drug, methylene blue, to make them more visible. Instead, the tangles dissolved.

Wischik spent the next two decades figuring out why that happened, and in 2002 he formed TauRx. The $60 million in seed money was raised by the late Dr. K.M. Seng, a Singapore venture capitalist who Wischik met when their sons were school friends. Now Wischik is seeking a drug company partner.

The seeming efficacy of Rember has revived an old controversy in the Alzheimer's field: Has too much money and scientific energy been funneled into clearing amyloid at the expense of better targets? One of the few positive Alzheimer's trial results this year besides Rember was for another anti-Tau drug created by startup Allon Therapeutics of Vancouver, B.C. In a small trial of patients with mild memory impairment the drug, AL-108, improved some aspects of cognition.

Despite the recent failures, many scientists and company executives see the glass as half full. There are at least 30 drugs in human trials today; 20 years ago there were none. "I think we must continue to pursue all targets," says Dr. John Q. Trojanowski, a leading researcher at the University of Pennsylvania. "I predict we will eventually have 10 different drugs for Alzheimer's."

Arnst is a senior writer for BusinessWeek based in New York.

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