The trouble with Tamiflu

[Guest guest]

http://www.guardian.co.uk/world/2009/may/07/tamiflu-swine-flu-drugs

The companies behind the two leading anti-flu drugs are making millions out of

the crisis. But just how effective are their products? Sarah Boseley reports

 

It was a sight that would have gladdened the heart of Dr Severin Shwan, chief

executive of Roche, one of the biggest drug companies in the world. A long line

of well-heeled parents assembled on a bank holiday weekend at a British private

school, Alleyn's in south London, patiently waiting their turn to receive a

packet of Roche's drug Tamiflu from staff. Five pupils had been diagnosed with

swine flu and the school had been closed. The pills were intended to stave off

infection among the children who had been sent home.

 

The board of Roche, a Swiss-based company which has globalised the name it

inherited from its founder, Fritz Hoffmann-La Roche in 1896, must be laughing.

It has a drug which has become a household name and been stockpiled by the

millions of boxes all over the world, against a potential pandemic that the

World Health Organisation (WHO) warns is almost upon us. Roche has supplied

governments with 220m courses worldwide. The UK has stored enough to treat half

the population. And yet Tamiflu is of limited use.

 

There are two drug contenders to reduce the impact of a flu pandemic - Tamiflu

(oseltamivir) and the GlaxoSmithKline (GSK) drug Relenza (zanamivir), which is

similar but more complicated to use because it must be inhaled - not easy if

people have breathing problems. But Relenza, too, is being stockpiled around the

world, to the delight of a small Australian company called Biota Holdings - the

company that developed Relenza and licensed it to GSK. Biota's share price leapt

16% last week when GSK announced it had sold $46m-worth of the flu drug, giving

Biota $32.3m in licensing fees.

 

Relenza and Tamiflu are known as neuraminidase inhibitors (NIs). Two other,

older flu drugs, amantadine and rimantadine, are now of little use because flu

viruses have become resistant to them over the years. Nobody claims Tamiflu and

Relenza cure flu, but they were licensed after trials that showed they mitigated

its severity and reduced the length of the illness by about a day.

Unfortunately, you have to take them within 48 hours of symptoms starting.

 

The government's contingency plan envisages that any of us who start to cough

and splutter would ring a flu hotline, where a nurse would give us a diagnosis

over the phone and then prescribe the drugs which our nominated " flu buddy " will

pick up from the chemist. But the most important element of this arrangement,

some will say, is that it keeps the flu sufferer out of the way of the rest of

us. Dr Tom Jefferson, of the Cochrane Collaboration in Rome, headed the most

authoritative, non drug-company conducted (and therefore without the vested

interests) review yet done on the flu drugs. He is appalled that such drugs

could be widely used and relied on as the solution to a flu pandemic at the

expense of things that really work - like washing your hands dozens of times a

day.

 

The Cochrane review, carried out in 2006 but regularly updated, most recently

this year, says the NIs do not stop people becoming infected, although they do

decrease the amount of virus sprayed from people's noses when they sneeze all

over you in the bus or office. They can also reduce the complications of flu,

such as bronchitis and pneumonia. The review concluded that they might be of

some help in a pandemic, but strongly recommended they should not be handed out

routinely or used for normal winter flu outbreaks.

 

To Jefferson's horror, however, the WHO has recommended that the drugs should be

used against seasonal flu - the usual forms of flu that hit us every winter - so

that doctors get used to giving them, and patients to taking them, ahead of a

pandemic. " Wide-scale use of antivirals and vaccines during a pandemic will

depend on familiarity with their effective application during the inter-pandemic

period, " it reasons.

 

" It is more than madness, " says Jefferson. " Especially as we don't know what the

real reasons for that recommendation are. " Doctors who work for the drug

companies, carrying out their studies or sometimes simply allowing their name to

be attached to the paper, also advise the WHO, he points out.

 

He argues that there is a very real possibility of resistance developing to the

drugs if they are handed out like Smarties. Viruses are clever organisms, and

evolve super-fast and efficiently. Treat a virus with drugs and you must hit it

hard enough and for long enough to eliminate it. If the dose is not strong

enough, or the patient stops taking the drugs mid-course, the virus will evolve

into a form that can overcome the drug. It is then a resistant strain. This is a

major problem with the Aids virus, HIV, for which many new drugs have had to be

developed. Bacteria behave the same way - penicillin, once a wonder drug, is now

of little use.

 

Jefferson points out that although Tamiflu is only eight years old, resistance

has already set in. Last year a strain of winter flu was circulating in the US

that was found to be resistant to Tamiflu. In the South East Asia bird flu

outbreak, there was resistance among 16% of children given the drug and among

two out of eight Vietnamese people aged between 8 and 35, according to the

Cochrane review.

 

This resistance is inevitable, says Jefferson, if you believe in the theory of

natural selection, in which organisms evolve to overcome threats to their

survival. " We know that has already happened with Tamiflu. It has happened with

amantadine, which has been around since the 60s. " Of course, governments and the

public want magic bullets. There is a belief that where there is an illness,

there must be a cure. Handing out drugs reduces panic. People are more likely to

stay put at home where they cannot infect too many people if they feel they are

being treated.

 

And there is is a role for Tamiflu in severe and complicated cases caught early.

But Jefferson balks at the idea of drug hand-outs at schools. " The spread will

stop, but only because the children have been sent home, " he says.

 

The most important trial in disease prevention of the last 50 years was carried

out in 2005 by a US doctor called Stephen Luby. " For that he should receive a

Nobel prize, " says Jefferson. Luby carried out a randomised trial in squatter

settlements in Karachi, promoting hand-washing in half the families. Children

under five who regularly washed their hands had half as many episodes of

diarrhoea, impetigo and acute respiratory infection. It saved lives. If the big

pandemic hits, washing hands will save more lives than Tamiflu, he predicts.

 

Meanwhile Tamiflu is sought everywhere. In 2005, Roche asked for help in

manufacturing enough of the stuff to satisfy world demand and it got 300 offers

from other manufacturers. It has now established 19 partners to produce the drug

in 10 locations on three continents. It has also given licences to Indian and

Chinese generic companies to make it for the developing world. If only it really

was a miracle cure ·

 

 

 

 

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