Coartem in Africa: Gaining Momentum on the Ground
For almost a decade, Novartis has led a revolution in the treatment of malaria.
The main battleground is Africa, where malaria kills more than a million
people every year, mainly pregnant women and children younger than five years
of age. “Malaria is more than an ordinary disease on this continent,” says
the Honorable Richard Nduhura, Uganda’s Minister of State for Health. “It
has major implications on all essential aspects of our life -- as individuals,
as families, as communities and as a nation.”
When Novartis joined the fight against malaria during the late 1990s, Africa
was on the brink of a public-health disaster. Malaria parasites had developed
resistance to the older antimalarial drugs such as chloroquine on which African
countries had relied for decades. In some countries, cure rates had dwindled
as low as a single patient for every 10 patients treated. Physicians were
desperate for an effective new medicine.
Working with partners in China, Novartis had developed Coartem, the first
of a new class of antimalarial medicines known as artemisinin-based combination
therapy, or ACT. Coartem included a component used for centuries in traditional
Chinese medicine to treat fever. A second antimalarial compound, working
through a different mechanism of action, acts synergistically, mopping up
any parasites that might have survived the initial assault. Combining both
components in a single pill, Coartem was the first ACT to offer the convenience
of a fixed-dose formulation, enhancing patient compliance. In clinical trials,
Coartem achieved cure rates of up to 95%, even in areas of multi-drug resistance.
During 2006, more than 62 million treatment courses of Coartem were delivered
to more than 30 countries across Africa, helping to save an estimated 200,000
lives.
To ensure broad access to Coartem, Novartis forged a partnership, with the
World Health Organization to provide Coartem at no profit for use by public
health systems in developing countries. In their agreement signed in 2001,
Novartis and the WHO estimated that demand for Coartem might exceed 2 million
treatments within five years.
The exceptional efficacy of Coartem, combined with availability of international
donor financing through the Global Fund to Fight AIDS, Tuberculosis and Malaria,
pushed demand for the new drug higher than anyone could have imagined. And
as demand surged, Novartis and its partners responded with a rapid scale-up
of production virtually unprecedented in the global pharmaceutical industry,
particularly for a medicine supplied on a not-for-profit basis.
During 2006, more than 62 million treatment courses of Coartem were delivered
to more than 30 countries across Africa, helping to save an estimated 200,000
lives. Production capacity for Coartem is even higher – 100 million
treatments per annum – if orders are placed in a timely manner.
Robert W. Snow, Professor of Tropical Public Health, University of Oxford
Manifold Challenges
With some of the most populous countries in Africa now rolling out Coartem,
malaria experts are upbeat about the potential impact for public health. “We
have the opportunity to use Coartem as an entry point for making the whole
government healthcare sector work better, not only by managing sick patients,
but also by streamlining distribution and maintaining supplies of drugs
to ensure effective treatment at remote healthcare facilities,” says
Robert W. Snow, Professor of Tropical Public Health at the University of
Oxford and one of the world’s leading authorities on malaria. “This
could have a knock-on effect for all the diseases that are managed at local
clinics and healthcare facilities,” Prof. Snow adds.
At the same time, he cautions that problems “of actually implementing
change have been manifold.” In Kenya, where Prof. Snow has lived for
almost 20 years, the Ministry of Health changed national malaria-control
policy and adopted Coartem as first-line therapy in April 2004. The first
Coartem deliveries, however, didn’t reach thousands of healthcare facilities
around the country until the end of last year.
Other countries have encountered similar problems, ranging from disruptions
or delays in financing, to political commitment and buy-in from healthcare
professionals. And surveys have shown that poor reporting and reordering
by remote healthcare facilities, combined with weak transport systems, continue
to result in stockouts in many countries where Coartem has been introduced.
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Signs of Success
Novartis has helped to address these challenges by hosting a succession of
Best-Practice-Sharing conferences for officials on the front lines in the
battle against malaria. At the most recent conference, held in Kampala,
Uganda, in late March, representatives from more than a dozen countries
reported clear signs of progress along with frustrating glitches in distribution
and drug management.
Data from KwaZulu-Natal province in South Africa indicated that dramatic
declines in both the number of malaria cases and malaria-related deaths that
followed introduction of Coartem and an integrated malaria-control program
in 2000-2001 were maintained through 2005.
Separately, studies from two states in Nigeria showed that the rollout of
Coartem increased the number of children younger than five seeking treatment
at public health clinics. At the same time, there was a significant reduction
in the number of children younger than five admitted to hospitals with severe
malaria. “And we believe the reduction in admissions for severe malaria
will invariably lead to a reduction in malaria mortality, and overall mortality
among children under five,” says Henry Akpan, Director and Deputy National
Coordinator, National Malaria Control Program in Nigeria.
Representatives from more than a dozen countries
reported clear signs of progress along with frustrating glitches in distribution
and drug management.
In Zambia, the first country in Africa to adopt Coartem as first-line therapy
against malaria, a survey of more than 100 health centers demonstrated substantial
improvement in availability of the drug at remote healthcare facilities,
as well as in the proportion of children who were treated with Coartem, compared
to results of a similar national survey in 2004. Nevertheless, stockouts
remain widespread at health facilities throughout Zambia; about 20% of children
who seek care for a febrile illness leave clinics without receiving an antimalarial
medicine, though Zambia’s guidelines recommend treatment of all childhood
fevers with antimalarial drugs, irrespective of other causes.
Collection of data from the field measuring the impact of new malaria policies
remains a major focus at the Best-Practice-Sharing conferences. “It
is the yardstick by which you judge the whole drug-policy change,” says
Prof. Snow, who served as co-chairman of the Kampala meeting. “Measuring
results shows our governments that the new policies are making a difference.
And it also shows donors that the money they are spending on us is actually
having an impact.”
From left: Dr. Henry Akpan, Director and Deputy National Coordinator, Nigeria’s National Malaria Control Program, and Dr. Anne Claire Marrast, Global Brand Medical Director from Novartis
Combination of Interventions
Dr. Nduhura, Uganda’s Minister of State for Health, opened the Best-Practice-Sharing
meeting in Kampala. He described how the spread of drug-resistant parasites
increased the number of malaria cases in Uganda to more than 12 million in
2005, from 5.5 million cases in 1998.
“Coartem is highly effective against malaria parasites, eliminates
the parasites and symptoms significantly faster and achieves higher cure
rates than older drugs. And I want to take this opportunity to thank Novartis
for reducing the price of Coartem, and also to thank the Global Fund for
availing funds to procure Coartem,” he added.
“But there is a need for a combination of interventions, effective
drugs like Coartem as well as vector control with indoor residual spraying
and use of insecticide-treated bednets.”
Along with neighboring Tanzania and Ethiopia, Uganda is planning to resume
indoor spraying of homes with DDT, widely acknowledged as the most effective
insecticide against mosquitoes. “There has been a lot of debate and
claims that countries using DDT won’t be able to export agricultural
products to the European Union,” Dr. Nduhura mused.
“However the EU has made it very clear that as long as regulations of the Stockholm
Convention of the WHO are followed, they have no problems with use of DDT
for vector control. In Uganda, we don’t intend to depart from the convention
and, all things remaining equal, we intend to start using DDT in areas for
vector control by the end of June this year.”
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Pediatric Formulation in Testing
In Kampala, Novartis scientists provided an update about development of a
new dispersible formulation of Coartem, aimed to increase convenience of
administration and improve palatability for young children. The new pediatric
formulation is the latest in a succession of steps attempting to advance
treatment of children. According to the WHO, more than 3 000 children in
Africa die of malaria every day.
In recent years, Novartis and the WHO conducted ambitious clinical trials
that paved the way to regulatory approval of Coartem in children with body
weight of five kilograms, compared to the previous minimum weight limit of
10 kilograms.
The new dispersible formulation, a joint development project between Novartis
and Medicines for Malaria Venture, has reached an advanced stage of clinical
testing and, if submitted to regulatory authorities and approved, would represent
another new milestone. Dispersing Coartem in milk or water for a child to
drink promises to make dosing more reliable than the current practice of
crushing adult tablets for use by children. And a new cherry flavor developed
for the dispersible formulation masks the bitter taste that Coartem has in
common with most other antimalarial medicines.
From left: Hon. Dr. Richard Nduhura,
Uganda’s Minister of State for Health; Hans Rietveld, Marketing
Director Malaria Initiatives Novartis, and Silvio Gabriel,
Executive Vice President Malaria Initiatives, also from Novartis.
Strengthening the Supply Chain
Not surprisingly, the rollout of Coartem in large countries from Uganda to
Tanzania and Ethiopia to Nigeria has exposed weak links in national supply
chains. “Patients know Coartem is effective and can cure malaria
in three days. Frequently they have already used the drug to treat a family
member or themselves,” says Silvio Gabriel, Executive Vice President
Malaria Initiatives at Novartis. “But too often, when they go to
a clinic or health facility, no Coartem is available. So improving drug
management must be a priority for countries. If Coartem doesn’t reach
patients, it can’t cure them.”
For example, Nigeria and Tanzania have encountered problems in the front-end
of the drug-management cycle: from forecasting and securing Global Fund grants
to transferring funds within the country as well as between donors, the WHO
and Novartis. In Nigeria, initial deliveries of Coartem were delayed by more
than a year, squeezing deliveries and distribution originally planned for
two years into a hectic, nine-month period. Despite promising results in
some areas, the number of patients reached so far remains only a fraction
of the original target.
“Improving drug management must be a priority for countries. If Coartem doesn’t reach
patients, it can’t cure them”, said Mr. Silvio Gabriel, Executive Vice President Malaria Initiatives at Novartis.
Tanzania introduced use of artemisinin-based combination therapy on a small
scale in 2003 and designated Coartem first-line therapy nationwide in 2004.
But it took 16 months from disbursement of the initial installment of grant
money from the Global Fund to Tanzania’s Ministry of Finance until
Novartis completed delivery of the order in December 2006. “We saw
very clearly in Tanzania that you can lose a lot of time just moving money
around,” Mr. Gabriel said. Tanzania has become the first country to
take advantage of a new procurement option involving direct payments to Novartis
and also managing deliveries directly, without a professional procurement
agency in an intermediary role.
Other countries are overhauling their logistics and distribution. Ethiopia,
for example, has eliminated a spate of steps previously required to transfer
Coartem and bednets from a central state-owned distributor to remote healthcare
facilities. Of course, acknowledging early setbacks is a precondition for
solving underlying problems; detailed analysis of forecasting, distribution and drug management will remain
a key item on agendas of future Best-Practice-Sharing conferences.
“Novartis is proud to be part of this success story,” Mr. Gabriel
says. “And these Best-Practice-Sharing workshops are another contribution
to help make it happen. But the people on the front lines in these African
countries are the pioneers. They are the heroes. And it is their achievement
in this malaria story that will make its way to the history books.”
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