Glaxo chief: Our drugs do not work on
most patients
By Steve Connor, Science Editor 08 December 2003 The
Independent
A senior executive with Britain's biggest drugs company
has admitted that most prescription medicines do not work on most people who
take them. Allen Roses, worldwide vice-president of genetics at GlaxoSmithKline
(GSK), said fewer than half of the patients prescribed some of the most expensive
drugs actually derived any benefit from them.
It is an open secret within the drugs industry that most
of its products are ineffective in most patients but this is the first time
that such a senior drugs boss has gone public. His comments come days after
it emerged that the NHS drugs bill has soared by nearly 50 per cent in three
years, rising by £2.3bn a year to an annual cost to the taxpayer of £7.2bn.
GSK announced last week that it had 20 or more new drugs under development that
could each earn the company up to $1bn (£600m) a year. Dr Roses, an academic
geneticist from Duke University in North Carolina, spoke at a recent scientific
meeting in London where he cited figures on how well different classes of drugs work in real patients.
Drugs for Alzheimer's disease work in fewer than one
in three patients, whereas those for cancer are only effective in a quarter
of patients. Drugs for migraines, for osteoporosis, and arthritis work in about
half the patients, Dr Roses said. Most drugs work in fewer than one in two patients
mainly because the recipients carry genes that interfere in some way with the
medicine, he said. "The vast majority of drugs - more than 90 per cent
- only work in 30 or 50 per cent of the people," Dr Roses said. "I
wouldn't say that most drugs don't work. I would say that most drugs work in
30 to 50 per cent of people. Drugs out there on the market work, but they don't
work in everybody."
Some industry analysts said Dr Roses's comments were
reminiscent of the 1991 gaffe by Gerald Ratner, the jewellery boss, who famously
said that his high street shops are successful because they sold "total
crap". But others believe Dr Roses deserves credit for being honest about
a little-publicised fact known to the drugs industry for many years. "Roses
is a smart guy and what he is saying will surprise the public but not his colleagues,"
said one industry scientist. "He is a pioneer of a new culture within the
drugs business based on using genes to test for who can benefit from a particular
drug." Dr Roses has a formidable reputation in the field of "pharmacogenomics"
- the application of human genetics to drug development - and his comments can
be seen as an attempt to make the industry realise that its future rests on
being able to target drugs to a smaller number of patients with specific genes.
The idea is to identify "responders" - people
who benefit from the drug - with a simple and cheap genetic test that can be
used to eliminate those non-responders who might benefit from another drug.
This goes against a marketing culture within the industry that has relied on
selling as many drugs as possible to the widest number of patients - a culture
that has made GSK one of the most profitable pharmaceuticals companies, but
which has also meant that most of its drugs are at best useless, and even possibly
dangerous, for many patients.
Dr Roses said doctors treating patients routinely applied
the trial-and-error approach which says that if one drug does not work there
is always another one. "I think everybody has it in their experience that
multiple drugs have been used for their headache or multiple drugs have been
used for their backache or whatever. "It's in their experience, but they
don't quite understand why. The reason why is because they have different susceptibilities
to the effect of that drug and that's genetic," he said. "Neither
those who pay for medical care nor patients want drugs to be prescribed that
do not benefit the recipient. Pharmacogenetics has the promise of removing much
of the uncertainty."
Demolished: the myth that allows drugs giants to sell
more By Steve Connor, Science Editor 08 December 2003
For years, the drugs industry has grown fat on a myth
- the false belief that all drugs will work on just about everybody. That has
essentially been the rationale for a culture that has encouraged doctors to
prescribe first and ask questions later - at a cost to the NHS of £7.2bn
a year in medicines.
Yet it has been an open secret within the drugs industry
that most drugs do not work for most patients, a secret that has now been publicly
aired for the first time by Allen Roses, the head of genetics at GlaxoSmithKline,
Britain's biggest drugs company.
Dr Roses, an academic with a distinguished record in
medical genetics, is used to speaking his mind, especially on the benefits of
a revolutionary new approach to drug development called pharmacogenomics. That
is the science of applying the results of the human genome project to drug development.
In essence, it means testing the DNA of patients in
order to identify those for whom a particular drug will work - the "responders".
That would enable doctors to eliminate the "non responders" who, as
a result, will at least not be given a drug that at best could be useless and
at worst dangerous in terms of harmful side-effects. In the past, drug companies
have developed drugs aimed at the widest possible population. That was the most
profitable strategy but one that ignored a basic fact in biology - people are
different.
To emphasise the point, Dr Roses likes to quote Sir William
Osler, a Canadian physician who in 1892 remarked: "If it were not for the
great variability among individuals, medicine might as well be a science and
not an art." Bringing a new drug to market is an expensive business costing
tens of millions of pounds. It takes place in a culture of maximum possible
sales for maximum possible profit - a culture that does not like to broadcast
the fact that most drugs don't work for most people.
Drug testing in patients involves three phases of increasingly
complex clinical trials that must be successfully completed before the drug
is approved by regulatory authorities such as the mighty US Food and Drug Administration.
But even when a drug has been approved in terms of safety and "efficacy"
- whether it does what the label says it should do - few people realise just
how poorly they perform in real life.
Dr Roses cited a study published three years ago by Brian
Spear, a senior scientist at Abbott Laboratories, a medical diagnostics company
in Chicago, on the efficacy rates of a range of different drugs. It found that
drugs vary enormously in terms of how well they work, with efficacy rates varying
from as low as 25 per cent for cancer drugs to 80 per cent for painkillers.
For many drugs, however, the efficacy rates hover around 50 per cent or lower,
meaning that, for most people, these drugs just don't work. As Dr Roses puts
it: "The vast majority of drugs - more than 90 per cent - only work in
30 or 50 per cent of the people."
Dr Roses is one of the pioneers in a field of genetics
that promises to help to identify those people who could benefit from a drug.
It is called single nucleotide polymorphisms (SNPs) and it is a way of distinguishing
the smallest possible genetic differences between individuals. The use of SNPs
has already led to the discovery, for instance, of a test to detect the 5 per
cent of the population who inherit a predisposition to a potentially fatal side
effect of an anti-HIV drug called abacavir.
Now it is possible to test HIV patients before the drug
is given to them in order to weed out those patients who will suffer a severe
adverse reaction - a violent rash on the body. Scientists believe that SNPs
can be used to test people not just for their vulnerability to a drug's side-effects,
but also to whether it will work or not.
John Bell, the regius professor medicine at Oxford University,
said that for pharmacogenomics to catch on, doctors will have to learn new ways
of dealing with patients. "One of the biggest obstacles is culture. We've
all been taught to take the dose for a drug straight out of the British National
Formulae and then if that doesn't work to add another drug to the prescription,
and so on," Professor Bell said. "So we can end up with lots of patients
on four or more drugs where only one would do. This is a big cultural issue
to overcome," he said. Apart from the ethics of prescribing useless drugs
to people who could be poisoned by them, there is also the question of costs
to the NHS, which has seen a record 50 per cent increase in its drugs bill over
the past three years.
As Bill Clarke, the executive vice president of research
at Amersham, a British diagnostics company, said: "It's just not right
to spend that amount of money on drugs that don't work." For the sake of
a relatively cheap genetics test that can be carried out on the wider population
of patients, it would be possible to target drugs more effectively and more
safely, Dr Clarke said. It could also lead to a revolution in the way drugs
are tested, he said. If "responders" to a new drug can be identified
easily, it will be possible to simplify the expensive phase 3 clinical trials
which can involve thousand of people being followed over many years.
Dr Roses agreed: "You can pick out people who respond
a lot to the drug, can you pick out people who do not respond at all to the
drug and can you pick out people who are sort of in the middle. "By eliminating
the people that we predict will be non-responders we'll be able to do smaller,
faster and cheaper drug trials." That could be the incentive that will
lead to a change in the "one-drug-fits-all" culture of the drug industry,
he said. "I can't speak for other companies but I can tell you absolutely
for sure that there is a change in the culture of GSK," Dr Roses said.
And the advent of pharmacogenomics will not necessarily
mean a fall in sales. "If you can determine who is going to have a response
[to a drug] and who is not going to have a response, you can take your next
molecule and aim it specifically at the people who haven't had a response with
the first one so that you can create a set of drugs that cover the population,
and then you are back to selling to everybody," he said.
Trial approach PHASE I: These first studies evaluate
how a new drug or therapy should be given (by mouth, injection into the blood
or injection into the muscle), how often, and what dose is safe. A phase I trial
usually enrols a small number of patients, sometimes as few as a dozen.
PHASE II: A phase II trial usually focuses on one type
of illness, continuing to test the safety of treatment and beginning to evaluate how well it works. This is the essential intermediate step that will determine
whether the drug will go into bigger and more costly phase III trials.
PHASE III: These studies test a new drug, a new combination
of drugs or a new therapy in comparison to the current standard treatment. A
participant will usually be assigned to the standard group or the new group
at random (called randomisation). Often it involves "double blind"
trials, where neither the patient nor doctor knows who is being given the new
drug. Phase III trials often enrol large numbers of people and may be conducted
at many doctors' offices, clinics and cancer centres nationwide.