E-drug: New York Times: Drug Companies and the Third World
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WARNING LONG MESSAGE
New York Times, May 21, 2000
http://www.nytmes.com/library/national/science/health/052100drug-merchants.html
Reprinted under the fair use doctrine of international copyright law:
MEDICINE MERCHANTS
A special report.
Drug Companies and the Third World: A Case Study in Neglect
By DONALD G. McNEIL Jr.
MUGO, Uganda -- Jabbing, apologizing and then jabbing again, it takes
Harriet Ayikoru nearly 20 minutes to find a usable vein beneath the sleeves
of the sad old Tweety Bird T-shirt that Sentina Drajiru wears, and when the
melarsoprol goes in, Ms. Drajiru winces. Again and again she lightly
touches her arm to show exactly where she feels the sharp tip of the
pain as the medicine simmers up it. It is like eating chili peppers,
she says, only it is inside her.
"Once you use this drug, the vein is spoiled," says Miss Ayikoru, a nurse
in the thatched clinic here. "As it is corrosive, it erodes the inside
layer. So the relapses like her are the hardest cases -- the scar tissue is
there even six months later."
Melarsoprol, invented almost 70 years ago, is melarsen oxide dissolved in
propylene glycol -- literally, arsenic in antifreeze. It kills 5 percent of
those treated with it. But it is the only medicine available to treat
advanced sleeping sickness, one of the historic scourges of Africa, which
was nearly wiped out 50 years ago, but has made a comeback. The only
alternative ran out in July. The manufacturer, which abandoned it
as unprofitable when it turned out to be useless against its intended
target, cancer, has made one last batch, enough for 1,000 patients. But
300,000 people are infected each year. Sleeping sickness is perhaps
the most vivid example of the disconnection between the world's
pharmaceutical giants and the fatal or debilitating diseases of the
third world's poor.
These ailments go untreated or badly treated not just because the poor
cannot afford the drugs they need, though that is a serious problem, but
because the drugs themselves do not exist. The pharmaceutical industry has
little incentive to invent them. Companies decline to invest the huge sums
needed to chase a cure they know their potential customers cannot afford.
According to IMS Health of Westport, Conn., a marketing research firm that
studies the industry, Africa accounts for 1 percent of world drug sales,
while North America, Japan and Western Europe account for 80 percent. It is
for them the companies invent a stream of high-priced, highly profitable
drugs.
"The poor have no consumer power, so the market has failed them," said Dr.
James Orbinski, international president of Doctors Without Borders/M�decins
Sans Fronti�res, the medical agency whose work in war zones and in the
third world won it the Nobel Peace Prize last year. "I'm tired of the logic
that says, 'He who can't pay, dies.' "
Pharmaceutical executives reluctantly concur with his assessment. Told that
the industry's critics say it would rather find a cure for a bald American
than a dying African, Fran�ois Gros, a spokesman for Aventis, the
French-German pharmaceutical company that makes three of the four sleeping
sickness drugs, ruefully acknowledged: "That's not completely wrong. We
know what's happening in the third world, but we don't act." He went
on to explain: "We can't deny that we try to focus on top markets --
cardiovascular, metabolism, anti-infection, etc. But we're an
industry in a competitive environment -- we have a commitment to
deliver performance for shareholders."
Predictable Behavior
Health experts also recognize this reality. "A blockbuster drug makes them
$1 billion to $1.5 billion a year," said a senior World Health Organization
official. "If you're running the R & D department of one of these
companies, you're under a lot of pressure, and they're going to invest in
things they see a market for. Their behavior is perfectly predictable."
As a result, many health policy makers now argue that the world's
governments must somehow force the world's pharmaceutical manufacturers to
turn their attention to diseases like sleeping sickness, malaria,
tuberculosis, leishmaniasis and the various burrowing worms that kill or
cripple millions each year in Africa, Asia and South America. The last
truly new drug for tuberculosis, for example, which kills two million
people a year, was invented over 30 years ago.
To do so, they say, rich nations must either pay the manufacturers
directly, offer them tax breaks, dangle before them the carrot of longer
patents on their most lucrative drugs, or, in acute crises, simply allow
poor countries to declare health emergencies and seize the patents to make
their own generic versions or buy them from India, Brazil or other
countries that ignore Western patent law.
[Earlier this month, five major pharmaceutical companies announced that
they were entering negotiations with the W.H.O. to voluntarily lower their
prices on their AIDS drugs to Africa by as much as 80 percent. But last
week, at a global convention of health ministers at the W.H.O.'s
headquarters in Geneva, the ministers of many poor nations said that was
not enough. They asked the W.H.O. to create a database of all prices for
AIDS drugs, including the cheapest generics from countries that do not
honor American or European patents, and to help them change their patent
laws so they could buy them.]
The pharmaceutical industry invests $27 billion a year in research, but
most of that is a hunt for drugs to lengthen or brighten the lives of
consumers who are already relatively healthy. Among the biggest sellers are
drugs to grow hair, relieve impotence or fight cholesterol, ulcers,
depressions, anxiety, allergies, arthritis and high blood pressure.
"Pharmaceutical companies will always aim for maximum profits by marketing
a new obesity drug rather than pioneering a novel malaria treatment," said
Dr. Bernard Pecoul, who heads the Doctors Without Borders campaign to get
affordable drugs into the more than 80 countries where the group works.
"When new vaccines or medicines are developed, most of the world's
population is left out of the picture."
Market research is now just as important as science in guiding the
decisions of pharmaceutical companies. While executives decline to say
publicly how much potential profit a drug must have to interest them, many
spoke privately to W.H.O. researchers doing a 1998 study of why new
tuberculosis drugs were not being made. "The major companies are
aiming for $1 billion at peak sales," the study concluded. "Targets
vary for companies, but many want to generate a minimum of $200
million per annum."
According to a study led by Dr. Pecoul, of the 1,233 new medicines patented
between 1975 and 1997, only 13 -- 1 percent -- were for tropical diseases.
Even of those, only 4 came from efforts by pharmaceutical companies to cure
humans. The 9 others came from work done by the United States Army for the
Vietnam War or from research on drugs for livestock or for the pet market,
which industry representatives say could be a gold mine. Already, Novartis
makes a drug to treat separation anxiety in dogs and Pfizer has one to
treat dog Alzheimer's.
No major company is doing new research on sleeping sickness.
The town of Omugo in northwest Uganda, a strip of crumbly red clay stores
and thatched mud houses that resemble chocolates in straw hats, is at the
center of the sleeping sickness epidemic that goes deep into both war-torn
Congo and war-torn Sudan nearby. The colonial-era programs that
sprayed insecticide, cleared riverine brush,treated patients and
moved whole villages away from fly-infested areas are no more than an
ancestral memory now. Fifty years of shifting civil wars have rebuilt
the two reservoirs of the disease: biting flies and untreated people.
And a new outbreak has begun in Uganda's southeast, said Dr. Dowson
S. Mbulamberi, who heads the Ugandan Health Ministry's efforts
against vector-borne diseases like sleeping sickness. His is a
daunting task. Uganda's public health budget amounts to $12 per
citizen per year, less than the cost of one tsetse fly trap.
Sleeping sickness is actually far too benign a name for human African
trypanosomiasis. The illness is spread by the bite of tsetse fly, the
scissor-winged glossina species found from Senegal to Somalia to South
Africa. In its saliva, the small fly injects a protozoan that it picks up
from feasting on another infected person. The symptoms start with
low fevers, itchy skin, joint pain and lethargy. But weeks later,
when the parasites enter the brain, patients begin hallucinating or
acting wildly. They have been known to chase family members with
machetes, shout all night, throw themselves into latrines, and
pillage other villagers' plots of cassava or bananas to feed ravenous
appetites. Their skins get so sensitive that cool water or a gentle
touch
makes them scream. Only at the end do they lapse into a lassitude so great
that they cannot feed themselves. Then they sink into a coma and die.
At one time, British tsetse control reportedly included "fly boys" -- young
men who stood shirtless in the bush slapping flies and were paid a bounty
for each killed. Because the fly likes dense brush near water, the illness
particularly affects women and the babies they carry on their backs as they
collect water or wash clothes. If infected, even babies must suffer
melarsoprol treatment.
Witchcraft Blamed, Too
Villagers fear sleeping sickness so much that some laboratory workers say
they are testing for malaria, which is known to be treatable. In the
villages, rumors say it is spread by eating pork, by sex and by witchcraft,
said Martin Andama, who visits villages to test people for the disease as
part of a Doctors Without Borders program.
Jovina Oleru, a woman who was cured and returned to nurse her son, still
stubbornly believes that she is sick because her family is angry at her
husband. "My husband only paid three cattle for me when I got
married, and I have given him three children," she explained. "So my
family really got nothing
for bride-wealth, and they feel bad about me and perhaps wish me to die."
That, she indicated, made more sense to her than the idea that flies make
humans sick.
"Hospitalization" here is cheap; the 60-foot-long ward has a cement floor,
brick walls, a straw roof and plastic sheeting for windows. Patients are
charged nothing, but each has to bring an "attendant" from home, who sleeps
on the floor, collects firewood and cooks over a fire in the brick hut in
the field outside.
One day recently Alfred M. Guma, 32, a farmer who grows sorghum and tobacco
on his small plot near Omugo, smoothed the rough brown blanket on his cot
in the ward where he was waiting out the 21-day stay required for
melarsoprol treatment. He was in Stage 2, meaning the parasites had reached
the spinal fluid bathing his brain, which is serious, though the disease
had been caught early. "My brother Steven had a mental breakdown,"
he said. "He began to see things that others could not see -- wild
animals, dead people coming to him at night. He feared having a bath
and became aggressive if you touched him, jumping back as if he had
touched fire."
For 14-year-old Steven, the family finally improvised an ambulance: they
used old clothing to tie him into a box on wheels behind a bicycle and took
him to a hospital. That was five years ago; Steven, cured, is now in high
school.
Only four drugs are known to work against sleeping sickness and all four
are in trouble. Their problems show how the open marketplace that works so
well for Americans still fails the world's poor.
One is from Bayer, the German pharmaceutical giant. Three are made by
Aventis, whose headquarters are in Strasbourg, France. That is a
coincidence; Aventis was formed in a chain of mergers of French, German and
American companies, three of which just happened to make drugs used against
trypanosomiasis. At $50 for a course of treatment, melarsoprol is
relatively inexpensive, and Aventis has promised to keep making it
for as long as it is needed. "But it's a terrible drug -- you don't
feel proud injecting it," said Dr.
Christine Genevier, director of the Doctors Without Borders program in
Uganda. "It's caustic, it burns them, and you don't know if you are going
to save your patient or kill them."
Now a strain of melarsoprol-resistant sleeping sickness is spreading. Up to
a quarter of the Omugo patients have it, so even if they survive the
painful injections they may die anyway. "It's a risky product,"
admitted Alain Aumonier, director of international corporate policy
for Aventis. "We won't claim the opposite."
The second drug, Eflornithine, known as DFMO and sold under the name
Ornidyl, is the best treatment for those melarsoprol-resistant patients.
Originally developed as an anticancer drug, its usefulness against sleeping
sickness was uncovered by chance in the 1980's; it proved so spectacular at
pulling people out of their final comas that it was nicknamed "the
Resurrection Drug." But it is expensive -- about $210 per course.
Worse, the manufacturer, an American subsidiary of Aventis, abandoned
the compound in 1995 when it proved ineffective against cancer.
Last year, pressed by the W.H.O. and Doctors Without Borders, whose supply
was running out, the company found 500 pounds of a precursor chemical in
Indianapolis and made one last batch of 7,800 vials. The chemical is
difficult to work with because it is unstable and corrodes piping; assuring
a steady supply would mean building a whole new production line, Mr.
Aumonier said, which the company declines to do. Instead, in
December, it signed the patent rights over to the W.H.O., which is
seeking a new manufacturer. An Egyptian candidate proved unable to
meet quality standards. A Texas company offered to make it at $60 a
vial, treble the old price. That is too much; the search goes on.
A More Exciting Prospect
Mr. Aumonier said Aventis made the last batch and turned over the patent out
of a sense of charity. "And now we feel trapped by what we've done," he
said. "We are reproached for not doing enough when we could have done
nothing."
Meanwhile, to the disgust of Dr. Pecoul, interest in the precursor chemical
has suddenly soared because it might prevent the growth of facial hair in
women. Gillette, the razor company, is doing research on it, "because they
think it might be a huge market," he said.
The third drug is Pentamidine, which is useful only against Stage 1, when
the parasites are confined to the blood. Treatment takes only 10 days.
Under the brand name Lomodine, the drug has been around since 1941. But in
the AIDS epidemic of the 1980's it was slightly reformulated and renamed
Pentacarinat, and its price soared from $1 a vial to $30 when it was found
to work against pneumocystis carinii pneumonia, once one of the chief
killers of people with AIDS. Despite the price increase, the
manufacturer, a British company that became part of Aventis last
year, has been supplying it free to the W.H.O. for use against
trypanosomiasis. But last year, Mr. Aumonier and health agency
officials said, Aventis told the W.H.O. it wanted to raise the price
gradually to market level, probably $14 a vial, by the year 2004. The
health agencies protested and the company is reconsidering, Mr. Aumonier
said.
Finally, there is Suramin, made by Bayer, which has been used since 1920,
also only against Stage 1. It costs less than $50 per course of treatment.
It has no other uses, so, a 1999 W.H.O. report said, "Bayer wished to stop
production, but maintained it on the grounds that no other alternatives
were available." Franz-Jozef Bohle, a Bayer spokesman, said the
company was trying to be a good corporate citizen, and was discussing
the supply of three drugs for tropical diseases with the W.H.O.
Pharmaceutical industry executives say they cannot be expected to shoulder
the burden of diseases of the poor alone. "The industry has never been
philanthropic," said Mr. Gros, the Aventis spokesman. "It has always
produced products with an aim to getting a return on investment." If
rich nations are unwilling to pay for drugs for poor ones, if poor
countries continue to spend fortunes on weapons and if their doctors
keep leaving to work in the West, he said, it is not the fault of the
pharmaceutical industry. "I like that statement 'Access to medicine
is a human right,' " said Mr. Aumonier of Aventis, quoting an
aphorism frequently used by health advocates. "But it's a right that
should be enforced by the whole community. May I suggest that the
pharmaceutical industry is only part of that community? It also
includes the health care system, the social system, even the patient.
"What's to be done if the poor are too poor to buy drugs on the free
market? Does government act sufficiently? To say to industry, 'You
make money, so you must enforce this human right alone' -- this,
somewhere, is wrong."
The Cause of Chaos
Mr. Bohle made a similar point, saying Bayer was willing to make some drugs
available cheaply, but wiping out an epidemic took much more: hospitals,
follow-up tests, record-keeping, tsetse fly control and other elements.
Daniel Berman, who works with Dr. Pecoul at Doctors Without Borders, said
he was troubled by such industry arguments. "O.K., they didn't
actually cause the problem," he said. "But are they an important
factor in the drugs not being produced? Absolutely." "When we're
there we can distribute them," he said. "The limiting factor for us
is price. But when a company abandons a drug, there's chaos." Taking
account of the trend of the last decade in which many companies have
been forced into mergers because their relatively low stock prices
made
them tempting targets to competition, Mr. Bohle conceded that Bayer did
little research on tropical disease. "You have to relativize this,"
he said. "A company can support some research without being paid off,
but not much. Especially with the pressure on shareholder value. I
remember when shareholder value was not important at all, and now
it's the main driver. There's always the threat of being taken over."
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