Garbed in white lab coat and goggles, a young scientist carefully cuts a mouse’s brain into wafer thin slices. She adds a drop of dye to each one before placing it under a slide for inspection beneath a microscope. On a nearby computer screen is a close-up image of a brain fragment from a second mouse, stained with what a researcher says are the telltale signs of a plaque associated with Alzheimer’s disease.
The location is Eli Lilly’s neuroscience research centre in the leafy Surrey commuter belt west of London — part of the front line in the battle against dementia: a condition that affects tens of millions worldwide and weighs heavily on health budgets. Until recently, it looked like a fight that was being lost as one clinical trial after another ended in failure. But in recent months, there have been tentative signs that the tide could finally be turning in the search for an effective treatment.
This new sense of optimism is expected to be underscored this week at the annual Alzheimer’s Association International Conference in Washington. As well as researchers and medics, investors will be there in force as Wall Street eyes the multibillion-dollar market opportunity awaiting any company that can deliver a successful drug.
Hopes of a breakthrough have been rising since March when Biogen, the US biotech group, announced positive trial results for an experimental Alzheimer’s medicine called, aducanumb. Sceptics cautioned that it was too soon to get excited about what was an early-stage study involving just 166 patients. But the bullish mood will become harder to resist if, as widely expected, Eli Lilly provides further cause for encouragement when it reveals data from a much bigger trial of its solanezumab drug in Washington on Wednesday.
“We’ve been chasing this goal for 26 years,” says Trafford Clarke, managing director of the US group’s Surrey research centre. “Other companies would have shut this down a long time ago but we’ve carried on because we believe it can work.”
Of all the health challenges being tackled by the pharmaceuticals industry, few are more difficult and pressing than dementia— a term which describes a range of memory-wasting conditions of which Alzheimer’s is the most common. Alzheimer’s alone is the sixth most common cause of death in the US, and the only disease among them without a treatment capable of slowing it. As medical breakthroughs improve the chance of surviving other big killers such as cancer and heart disease, ever more people are falling into dementia’s cruel grip. Yet, for all the recent optimism, the condition remains poorly understood.
“The brain is the most complex 1.5kg in the universe so when it goes wrong, trying to fix it is extremely difficult,” says Eric Karran, who has held senior neuroscience roles at Johnson & Johnson, Eli Lilly and Pfizer. “In oncology, you are trying to kill cells; in neurology you are trying to keep cells alive. It’s a lot easier to do the former than the latter.”
The number of people living with Alzheimer’s worldwide is forecast to rise from 44m today to 76m — almost equal to the combined populations of France and Belgium — by 2030, according to Alzheimer’s Disease International, an advocacy group. Ageing populations from the US to China are driving up the number of sufferers.
The worsening epidemic threatens not only a public health crisis but also an economic one. A quarter of UK hospital beds are already occupied by patients suffering from some form of dementia and the cost of these conditions is forecast to soar from £23.6bn last year to £59.4bn by 2050, according to the Office of Health Economics. The potential of an effective drug to reduce expensive hospitalisation and residential care means that policymakers are as eager as patients for the industry to succeed.
Yet, for a long time, Eli Lilly received little credit from investors for its dogged pursuit of Alzheimer’s. The disease had become known as a scientific and financial black hole into which the industry had thrown away billions of dollars. Between 1998 and 2014, there were more than 120 failed Alzheimer’s trials and just four new medicines reached market. These rare successes have offered temporary symptomatic relief to patients — typically for six to 12 months — but do nothing to slow the advance of the disease.
Dr Karran, now head of research at the charity Alzheimer’s Research UK, recalls the internal debates within companies where he worked, weighing the huge potential rewards from a successful drug versus the equally big risks. “If you have a failed Alzheimer’s drug in a late-stage trial that’s $400m down the tube,” he says. “You might have brought three new life-saving cancer therapies through for that money so there is an ethical as well as a financial dimension.”
Several companies including Pfizer largely abandoned Alzheimer’s after failed trials and many observers thought Eli Lilly would do the same when solanezumab failed to slow the rate of cognitive decline in a large, late-stage trial three years ago. But researchers saw a silver lining in the disappointing data: a 34 per cent slowing in the rate of mental decline among those suffering from mild, early-stage Alzheimer’s. This suggested the drug might work if administered before the disease became too entrenched.