Tag Archives: pharmaceutical companies

Alzheimer’s drug trial failures

The world’s leading pharmaceutical companies are downgrading the search for new treatments for Alzheimer’s disease after the failure of a series of high-profile drugs trials.

The human and financial costs of the disease are growing rapidly as the population ages, but the prospects of treatments to halt it, or slow its progress, are receding as at least five trials in the past five years have delivered disappointing results.

This year, a trial of Dimebon, backed by Pfizer, the US pharmaceutical giant, and reported in January, failed to show any benefit, instead costing the company $750m in lost investment.

In July, bapineuzumab, developed by Irish drug-maker Elan in association with Pfizer and the US multinational Johnson & Johnson, also failed to show an impact on symptoms.

In August, another US group, Eli Lilly, reported the failure of solanezumab, its second Alzheimer’s drug to disappoint in two years. In 2010, a trial of semagacestat not only failed to slow the disease but worsened symptoms.

The setbacks have damaged confidence among drug makers in the field of neuroscience – brain research – which was already shaky.

Pharmaceutical manufacturers worldwide are under pressure and have been cutting back in the recession, but neuroscience has been disproportionately hit, with AstraZeneca, Pfizer, Merck, Sanofi, Novartis and GlaxoSmithKline all downsizing their European departments. Speaking at a briefing organised by the Science Media Centre yesterday, Eric Karran, director of research at Alzheimer’s Research UK, said: “Neuroscience is a very challenging area. All companies are shedding jobs but neuroscience has had the highest attrition rate.

Alzheimer's

Alzheimer’s

“AstraZeneca had a very large neuroscience group with some 300 scientists. It is reducing that to a team of 40, who will act as a virtual team – not doing their own research but monitoring developments and forging links with other companies.”


Asked if the pipeline of new Alzheimer’s drugs could run dry, he said: “That has always got to be a risk. My sense is not that companies want to move away [from Alzheimer's research] but that their shareholders are getting restive. That’s capitalism – there is nothing we can do about that. But there is a huge public need.”

At least 12 times as much was spent on cancer research as dementia research, yet dementia cost the country twice as much as cancer, he said.

Craig Ritchie, a leading Alzheimer’s researcher at Imperial College, who runs a clinic for patients with dementia in west London, said: “The companies are streamlining their neuroscience departments and one can understand why. But it is hugely disappointing because there is massive unmet need.

“There is a shift to symptomatic treatments instead of disease-modifying ones. There is a lot less energy in the system than there used to be. We need a success story – a catalyst – to make people feel there is something to work towards.”

Alzheimer’s affects an estimated 500,000 people in the UK (a further 300,000 have other forms of dementia) and tens of millions worldwide, with the numbers expected to triple by 2050. It causes amnesia, loss of language, mood changes, apathy, psychosis and aggression.

The latest trials are thought to have failed because the drugs were given to patients too late in the disease process to have an effect, or were unable to pick up subtle changes in cognition over a relatively short period.

Alzheimer’s, which is marked by the build-up of sticky protein clumps – amyloid plaques – in the brain, is thought to take at least 15 years to develop and by the time symptoms appear, it is too late to reverse.

Existing drugs, such as donepezil (Aricept), have limited benefits.

Antibiotics resistance

The danger posed by growing resistance to antibiotics should be ranked along with terrorism on a list of threats to the nation, the government’s chief medical officer for England has said.

Professor Dame Sally Davies described it as a “ticking time bomb”.

She warned that routine operations could become deadly in just 20 years if we lose the ability to fight infection.

Dame Sally urged the government to raise the issue during next month’s G8 Summit in London.

Dame Sally said: “If we don’t take action, then we may all be back in an almost 19th Century environment where infections kill us as a result of routine operations. We won’t be able to do a lot of our cancer treatments or organ transplants.”

She said pharmaceutical companies needed to be encouraged to develop new drugs, because the manufacture of antibiotics was not viewed as profitable.

“We haven’t had a new class of antibiotics since the late 80s and there are very few antibiotics in the pipeline of the big pharmaceutical companies that develop and make drugs,” she said.

“We haven’t as a society globally incentivised making antibiotics. It’s quite simple – if they make something to treat high blood pressure or diabetes and it works, we will use it on our patients every day.

“Whereas antibiotics will only be used for a week or two when they’re needed, and then they have a limited life span because of resistance developing anyway.”

Dame Sally said action was needed to overcome this “market failure” and pointed to the Innovative Medicines Initiative – an EU funded body whose aim is to promote the development of new medicines.

Dr Ibrahim Hassan, a consultant microbiologist at Wythenshawe Hospital in Manchester, said there are more cases of patients with bacterial infections resistant to antibiotics – meaning there are fewer treatment options.

“All you can hope of is a bit of holy water because you don’t have too much option in terms of treatment.

“We’re beginning to see that in some hospitals, patients coming in with this infection with no antibiotic that can be used to treat them.”

Dame Sally’s warning coincides with the publication of the second volume of her annual report which details the burden posed by infectious diseases.

Death rates for infectious diseases have declined in developed countries in recent decades due to improvements in hygiene and sanitation, widespread immunisation and effective drug treatments.

But the report says they still account for 7% of all deaths in England and account for one in five days off work.

It says in decades to come we risk “losing the war” against microbes – and standard surgical procedures such as hip replacements could become riskier, as would treatments that suppress the immune system such as chemotherapy or organ transplant.

Antibiotics

Antibiotics

Dame Sally said it was a global issue for governments, the medical profession, the pharmaceutical industry and individuals.

She also said the over-use of antibiotics was an issue in animal husbandry, agriculture and fish farming.

She urged politicians to treat the threat as seriously as the superbug meticillin (also called methicillin)-resistant Staphylococcus aureus or MRSA.


Cases have fallen by 80% since 2003 through improved hygiene measures in hospitals.

Health officials say other infections have now overtaken MRSA as major sources of healthcare-acquired infections.

In particular, cases of E.coli and Klebsiella bacteria have increased by two-thirds in recent years and are now the most frequent cause of hospital acquired infection.

Both types of bacteria – known as Gram negative – are commonly found in the gut but can cause blood infections.

In England, Wales and Northern Ireland 99,000 cases of blood stream infections were reported in 2011-12. E.coli alone accounted for 36% of cases compared with just 1.6% due to MRSA.

The report estimates that up to 5,000 patients a a year die from Gram-negative blood poisoning each year, half with an antibiotic-resistant organism.

Dame Sally said no new classes of antibiotics had been introduced since 1987 whereas new pathogens were emerging every year, and existing bugs were developing resistance to current treatments.

A five-year UK Antimicrobial Resistance Strategy will be published shortly which will advocate the responsible use of antibiotics and strengthened surveillance.

The Chief Medical Officer said antimicrobial resistance would be put on the government’s national risk register of civil emergencies – which provides guidance on potential threats such as terrorist attacks, pandemic flu and major flooding.

Dame Sally said she was shocked by the “woeful education” in antimicrobial resistance given to many medical students and doctors; she wanted to ensure fewer antibiotics were prescribed, so that they are used only when needed.

Dame Sally is not the first chief medical officer to warn of the dangers of antibiotic overuse.

In 2008 her predecessor, Liam Donaldson, urged doctors not to use antibiotics to treat colds and coughs as these are caused by viruses and do not respond to antibiotics.

In 1999, Sir Kenneth Calman made a similar plea, saying the public had a responsibility not to demand antibiotics.