NO PEACE OF MIND FROM BIG PHARMA
IT’S BEEN CALLED ‘ THE GREATEST UNMET NEED FACING MODERN MEDICINE’ — BUT SOME COMPANIES ARE GIVING UP ON FINDING A WAY TO TREAT ALZHEIMER’S
Judging by his online corporate biography, it almost seems the late 2000s didn’t exist for Montreal’s Francesco Bellini.
There is no mention of the once-hot pharmaceutical company he ran — Neurochem Inc. — or the promising Alzheimer’s drug that for a few heady years had investors’ hearts racing.
If the potential of Alzhemed were fulfilled, the Quebec firm’s chief executive told the National Post in 2006, it would be a multibillion- dollar blockbuster and he could “retire anywhere in the world.”
Then, barely a year later, results from Phase 3 clinical trials came back, and the dream of medical breakthrough and untold riches abruptly evaporated: Alzehmed had little effect on people.
“It was very disappointing for everybody, especially for the patients,” Bellini said recently.
His deflating — and costly — experience was hardly unique.
As documented by two new Canadian co- authored journal papers, Alzhemed was only one among scores of potential dementia drugs over the past two decades that entered the pipeline with high hopes, only to later crash and burn.
Government a nd i ndependent groups in Britain and Europe have issued calls to action in recent months, noting that Alzheimer’s remains the sole major cause of death in industrialized countries that lacks a disease-modifying treatment — despite billions invested in trying to find one.
“For the clinical trialists in the world … the past 10 years have been frustrating,” says Dr. Serge Gauthier of the University of Montreal, co- author of the two recent articles that outlined the bumpy history of dementia drug development.
Yet the need for medicines to slow down Alzheimer’s is, if anything, more pressing than ever.
The rapid growth in the ranks of Alzheimer’s and other dementia patients — and the high cost of caring for them — not only represents millions of lives devastated by the crippling conditions, but actually poses a “serious threat” to economic and social development, argues Gauthier’s paper in Lancet Neurology.
An effective Alzheimer’s treatment “is perhaps the greatest unmet need facing modern medicine,” suggests the article, jointly written by experts around the world.
The scientists, part of a commission set up by the Lancet group of journals to tackle the issue, urged governments and industry to boost investment in treatment research significantly, even as the cost of caring for patients also balloons.
“It’s an urgent publichealth problem we have to address very quickly,” says Dr. Howard Feldman, an Alzheimer’s researcher at the University of British Columbia.
Experts say it’s important to remove obstacles and allow scientists to learn from each other’s work. Yet this country still has no national plan to co-ordinate dementia research among academia, government and industry, says Dr. Larry Chambers, scientific adviser for the Alzheimer Society of Canada.
There is good news, though, given effective new diagnostic tools and some promising new drug candidates on the horizon.
But questions remain about why so many past attempts have failed, what it will take to do better in the future, and whether some patients will ever be helped by medication.
To Phyllis Fehr, those are much more than academic issues.
The intensive- care nurse with a blended family of nine children sensed something was wrong when she began repeatedly forgetting where she had put everyday items. Then she found herself in a “cocoon-wrapped fog,” could no longer read and struggled to utter common words — saying knife, for instance, when she meant fork.
Three years ago, Fehr, 56, was finally diagnosed with early-onset Alzheimer’s.
One of the existing drugs that treats memory loss and other dementia symptoms — but not the underlying disease — has helped lift the fog, she says. Fehr knows it will not work forever, and suspects any medicine that can actually put the brakes on the illness itself will arrive too late for her.
But the resident of Hamilton is hoping effective treatment will be ready in case her children fall victim to Alzheimer’s. Fehr’s mother, aunt and grandmother all had dementia.
“Honestly, I’ ve come to terms with everything. I’m good with everything right now,” she says. “But I worry about my kids and grandkids.”
As Fehr attests, dementia patients do have a little pharmaceutical help. Four drugs on the market now provide some relief of symptoms for relatively short periods, but are powerless to curb the disease’s relentless, brain-ravaging progress.
Because existing therapies are so limited, and the pool of potential customers so large, Alzheimer’s has long been alluring to industry.
One of Gauthier’s recent papers, an offshoot of a project for Britain’s Office of Health Economics, found there had been 2,000 trials involving almost 900 would- be dementia drugs registered in the last 20 years.
Of the studies completed, suspended or withdrawn to date, none succeeded. Just fewer than 200 products are still listed as in development.
Industry involvement is crucial to bringing any drug to market, yet some companies burned by past failures have given up on dementia entirely in recent years, Feldman says.
Only 3.8 per cent of all pharmaceutical products in the discovery stage and 1.2 per cent in advanced Phase 3 trials are for dementia — compared to 31 per cent and 24 per cent for cancer, the British- commissioned study found.
So why is it so hard to make a dementia drug that works?
A key factor has been an exaggerated faith in a particular strategy: attacking just one of the biological origins of Alzheimer’s, Feldman says.
Science has well established that proteins known as beta- amyloid and tau spread abnormally in Alzheimer’s- afflicted brains, interfering with neuron transmission and killing off cells.
That led to an assumption that reducing what’s known as amyloid plaque, for instance, would necessarily make demented patients better, the UBC scientist says.
“I remember looking at a paper in Science — a vaccine against amyloid in a mouse model … and lo and behold, the pathology just melted away, disappeared,” he said. “It was very exciting.”
In reality, the solution was not so simple, and time after time drugs shown to reduce amyloid plaque in animals have failed to cause any improvement in humans already experiencing symptoms.
Another factor, perhaps related to that exaggerated hope, was a tendency of pharmaceutical companies to rush toward market, leading to huge spending on drugs that eventually failed, Gauthier says.
“If it doesn’t work, you waste money and the patient’s time,” he says.
There are auspicious developments, though. Rapid advances in diagnostic imaging have made it possible to identify people with Alzheimer’s- like changes in their brain before symptoms develop.
And a major U. S.- based project has taken the rare step of making available brain images and other research findings to all comers, the kind of scientific sharing that experts say is crucial to moving faster toward an Alzheimer’s treatment.
Among the experimental drugs that give Gauthier hope are LMTX by Tau- Rx, which is billed as the first tau- targeting Alzheimer’s product but also affects other proteins linked to dementia. A Phase 3 trial is underway.
The University of Montreal scientist also points to Eli Lilly & Co.’s highly anticipated Solanezumab, an antibody that binds to amyloid and clears it from the brain. After two failed trials, the company is running another Phase 3 study.
Montreal’s Bellini knows well the cash- immolating challenges of trying to get an Alzheimer’s medicine to market. His own Phase 3 trial of Alzhemed, involving more than 1,000 U. S. and Canadian patients, cost $ 100 million. A second in Europe was cut short.
Dr. Paul Aisen, the University of Southern California professor who led the North America trial, concluded in a 2012 journal paper that the studies “did not show efficacy.”
But Bellini notes there was MRI evidence of less brain shrinkage — a key Alzheimer’s trait — in patients taking the drug. With the patent expiring in 2018, he knew he couldn’t get investors to double- down on Alzhemed, but he’s convinced a much bigger trial and better selection of subjects would have shown the world its benefit.
“The cognitive tests are very subjective,” he says. “(But) on the MRI there was a clear difference between patients taking the drug and patients who were not taking it.”