After decades of researching a treatment for Alzheimer’s, Claude Wischik is set to find out whether his lonely 30-year battle can lead to one of the first real treatments for the memory-destroying brain disorder that afflicts millions worldwide.
The co-founder of Singapore-based TauRx Pharmaceuticals Ltd. plans to present results from ongoing final human trials on its experimental Alzheimer’s drug, LMTX, as early as July. An earlier study showed that patients given the company’s treatment had better cognitive scores than those who didn’t get it, according to research it published in the Journal of Alzheimer’s Disease.
The stakes are huge, and researchers estimate that more than 40 million people worldwide are living with Alzheimer’s and dementia. The world’s largest pharmaceutical companies from Pfizer Inc. to Biogen Inc. have poured resources into the field, but success has so far largely eluded scientists. There is still no cure for Alzheimer’s and no medicines to slow the progression of the disease.
Existing drugs mainly offer symptomatic relief for patients, and advisory firm GBI Research estimates that the market for Alzheimer’s therapies has the potential to expand from $5.2 billion in 2014 to $11.3 billion in 2021 in eight major countries including the U.S. and Japan.
Between 1998 and 2014, there were about 123 experimental Alzheimer’s medicines under development that were halted or did not receive regulatory approval, according to a report by the trade group Pharmaceutical Research and Manufacturers of America.
Successful trials would also be a boon for TauRx’s backers, including its biggest shareholder, Malaysian investment holding company Genting Berhad, and Singapore’s state investment company Temasek. Promising results might open the door for a possible initial public offering and tie-ups with large pharmaceutical companies, its executives say. If the trials are successful, the company would apply to both E.U. and U.S. regulators, and the timing of any approval would depend highly on the Phase 3 data, they said.
Wischik, a professor at the University of Aberdeen in Scotland, has spent his career looking for a drug to dissolve tangles of a protein called tau, one of the hallmarks of Alzheimer’s brain abnormalities. The majority of Alzheimer’s researchers have focused on another kind of protein clump known as beta-amyloid, which has had mixed results.
"Looking for ways to prevent tau aggregation is definitely a viable path for drug discovery," said Rosa Sancho, head of research at the charity Alzheimer’s Research UK. If the drug turns out effective and safe, "for the field it would be incredible, there are no treatments at the moment and they are so desperately needed."
Success isn’t guaranteed for TauRx. Sancho warns of pitfalls given the difficulties researchers have historically had with Alzheimer’s. "I would be cautious because in the past few years we’ve had so many failures in trials," she said, referring to tests from many pharma companies that failed to produce a viable drug.
In 2013, as many as 5 million Americans were living with Alzheimer’s disease, according to the U.S. Centers for Disease Control and Prevention.
Other experimental Alzheimer’s treatments are also far along in clinical tests. Eli Lilly & Co.’s is conducting final stage trials on the beta-amyloid-directed drug solanezumab. Trial results announced in July last year showed that patients who had been taking its drug longer did better on a cognitive test than those who hadn’t. This month the company said it had changed the primary goal of a test on the drug to focus solely on whether it can forestall changes that may occur early in the course of the disease.
Biogen’s drug BIIB037 has had mixed results. In an early- stage trial of 166 patients, the treatment was shown to reverse build-up of beta amyloid in the brain and also reduced cognitive decline. But in findings released later in July, the experimental drug failed to show a statistically significant cognitive benefit for patients on a closely watched dose.
Even if proven successful, the amyloid treatments will work with a completely different mechanism than a tau-based drug and they won’t be direct competitors, said Wischik. "The consensus of the field is that ultimately some sort of cocktail will be necessary," he said, drawing parallels with AIDS therapies that use a combination of treatments. "There’s no one winner-takes- all drug."
The mid-stage TauRx study published in the Journal of Alzheimer’s Disease showed cognitive benefits to patients taking 138 mg a day of the drug for 24 and 50 weeks, although the highest dosage of 228 mg failed to produce the same positive results. Wischik said the high dose was poorly absorbed due to natural limitations of a conversion process in the gut. The problems were fixed by creating the new version of the drug called LMTX that was used in the Phase 3 trials and which has so far proven to be safer and better tolerated, he said.
The first Alzheimer’s treatment that targets the disease and treats a broad spectrum of patients is likely to be an extremely valuable product and quite capable of generating more than $10 billion a year in sales, said Tim Earle, chief operating officer of TauRx.
As a young researcher in Cambridge in the 1980s, TauRx’s Wischik accidentally discovered that a class of chemicals could dissolve filaments of tau in test tubes. After partnerships with big companies including one with what was then Zeneca didn’t lead to a drug, Wischik decided he would carry on by himself.
TauRx was started with seed capital from a Singaporean friend of Wischik’s family and has raised about $500 million since it was founded in 2002, according to the company, mainly from Asian investors in places like Singapore and Hong Kong.
LMTX is an altered version of the company’s previous experimental product called Rember, a form of the dye methylene blue. Last year, research by the Mayo Clinic found that the accumulation of dysfunctional tau protein is the real source of cognitive decline and memory loss seen in Alzheimer’s patients, although beta amyloid may also be involved in the disease’s progression.
As a drug discovery company, TauRx will have to partner with big pharma or biotech companies for their marketing and distribution network, said Earle.
Asked about a potential listing, Earle said the company is having "very exploratory discussions talking about concepts, talking about possible strategic choices that we may have to make as the Phase 3 results pan out." The Nasdaq might be the most suitable venue for a "high-value biotech company," he said.
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