Vasella Expects more Partners and Donors to Join Fighting Malaria

April 25, 2006 - It has been another hot and dry day in October. In a small rural village in Zambia, a 4-year-old child finally gets to sleep. But in the middle of the night, unprotected by bed nets, she is bitten by a female anopheles mosquito. As it feeds on human blood to nurture its own eggs, the insect delivers a parasite, plasmodium falciparum – the most potent malarial parasite in the world – under the child’s skin. It enters the young girl’s blood stream and before long, begins to multiply, first invading and infecting her liver and red blood cells.

All is fine for a short while. But within a week or two -- the first symptoms appear. Resembling the flu, the child experiences a headache, nausea, fever and vomiting. If left untreated, her deterioration can be sudden, as the parasite multiplies rapidly throughout her small body and does its damage. It soon starts to clog the capillaries that carry blood to the brain and other organs. Most at risk are young children, pregnant women and others whose immune systems are fragile.

It was once believed that malaria originated in marshes and swamps and was transmitted through the air, hence the name from the Italian – mal’aria, or bad air. The real cause was identified in 1880 – a single cell parasite called plasmodium. And with the advent of insecticides and anti-malarial drugs over the years, the deadly consequences of invasion by this parasite were on the wane. Then, with resistance to anti-malarials developing, a reduction in pesticide use and the deterioration of various health care systems in developing countries, malaria has once again become potent and deadly. Forty percent of the world’s population, most living in the poorest countries – are at risk. Today, malaria is the leading cause of death in children under five in Africa and causes more than 10,000 maternal deaths as well.

Focus on Coartem
Ten thousand farmers working on thousands of acres of land are harvesting the sweet wormwood plant. From those first seeds in the ground will come a drug called Coartem, produced by Novartis, that can cure that little four-year old in just three days time. However, the chain of events – and the chain of supply -- that will lead to a cure relies on an extraordinarily complex and dynamic series of partnerships, interrelationships and collaborations across the public and private sectors, across continents, countries and cultures.

Jeffrey Li, President of Novartis in China, outlined: “For hundreds of years, the sweet wormwood plant was known to have powerful medicinal qualities like fever control and malaria treatment in China and throughout Asia. By the 1970s, it was identified as the source of artemisinin. And in the 1990s Novartis’s predecessor company in China collaborated with local Chinese scientists and local partners to bring the drug through clinical trials and into initial production.”

Today that anti-malarial represents the best hope for a little girl in Zambia. The drug is a combination product that consists of artemether, an artemisinin derivative that works quickly to clear malaria parasites, and lumefantrine, a synthetic anti-malarial that works more slowly, but that provides excellent long term cure rates.

Remarkable results with Coartem
Professor Nick White of the Wellcome Trust Research Laboratories, agrees: “We have seen remarkable results with this new class of ACT drugs like Coartem. In some regions, the number of malaria cases dropped by more than 90 percent when ACTS were used in combination with other malaria control measures. Production capacity has been ramped up as usage has risen exponentially. But we need to ensure sufficient agricultural production of artemisinin to sustain this progress.”

Dr. White’s observations point to what has been a challenge for partnerships and collaborations on two fronts: The first – to produce the drug – an internal Novartis challenge; and the second, to get all the different international parties to work together to get the drug to those countries who can use it most.

Dr. Daniel Vasella, Chairman and CEO of Novartis explained, “I don’t know how many hundreds of years the Chinese sweet wormwood plant goes back, but it is a very old and well known medicine. What is surprising is that it takes so long until one utilizes this kind of knowledge. The challenge we faced was accessing enough quantities of Artemisia. The plant was basically being harvested from wild crops – but not in a systemically grown, harvested and industrial way. That has changed meanwhile.”

Actually the original 2001 agreement between Novartis and the WHO forecast demand for Coartem at just over 2 million treatments by 2005, with production in 2002 at just 100,000 treatments. Novartis produced 30 million treatments in 2005 and is on target to more than triple this number of treatments in 2006 to 100 million treatment courses if orders are placed by malaria-endemic developing countries in a timely manner.

To Vasella’s point, the complexity of the production process could not be minimized. Crops of Artemisia annua must be planted one growing season ahead of its harvesting and extraction for use in the product. The cultivation of the plant itself takes six months, and the supply chain to manufacture the ACT adds up to five months to production timeline.

It all starts in January and February of each year when the seeds are planted. Come August, some 10,000 farmers -- in China, Vietnam and most recently in East Africa --harvest the plants. Around the world, almost 25,000 acres of Artemisia annua are cultivated; with China still the prime supplier. Novartis has also financed the expansion or construction of production facilities in Nairobi and Uganda, purchased needed agricultural tools and seed to be sold at a discount to farmers, gave incentives to farmers to switch from more profitable crops and provided them with training and technical support.

The decision to move to other countries was necessary, says Silvio Gabriel, executive vice president, Malaria Initiatives for Novartis, “To spread the risk of climatic factors that might impact the harvest of the raw ingredient for Coartem, it is important to diversify the geographic areas under cultivation. Our Chinese partners remain central to the supply for Coartem. The Chinese researched and discovered its medicinal value; Chinese scientists played a pivotal role in the development of artemether; and its scientists also contributed to research leading to the combination of artemether and lumefantrine.”

Vasella adds: “The partnership with the Chinese scientists and the Chinese government has been outstanding. I can’t give enough credit to China, the Chinese government and its scientists.”

It is indeed a multinational and global experience at every turn. The extraction and purification of the product takes place in China, Switzerland and Africa. Those materials are shipped to Suffern, New York, or to Novartis’s smaller production facility outside Beijing, to be combined with lumefantrine, granulated, tableted, blister-packed and then shipped once more to Novartis warehouse facilities in Stein, Switzerland where orders for the drugs are processed, picked up by WHO and shipped to health authorities in Africa and other countries around the world. Novartis sells the ACT at cost – and is looking for new and better ways to lower that cost still further – passing on savings to the Global Fund and other donor organizations that are financing orders.

Partnerships for hope
“The partnerships we have established are worked well” added Thomas Kuhn, who is coordinating the entire project for Novartis. “The challenge going forward is to create a more stable marketplace, where financing, order generation, demand forecasting and supply chain planning are better aligned to ensure long term sustainability of drug supplies.”

Among the key players is the WHO, which sets global treatment policies and guidelines, as well as establishing distribution networks; the Global Fund, providing monetary support; NGOs, like MSF, which seeks to reach health care providers and patients about the need for treatment; and of course, country governments, who must actually order drug and distribute it effectively and ensure adequate health care professionals training.

Dr. Naawa Sipilanyambe, country coordinator in Zambia for Malaria Control, a country that was the first to make Coartem first line treatment for its citizens, told Live: “I think the best example of a public-private partnership is the one we have with Novartis, because it has lead to a more precise and comprehensive approach toward introduction of ACT treatment. In the past, malaria treatment policy changes were done through government alone. But as a result of this new partnership with Novartis, we have greater sharing of responsibilities, of technical expertise, of resources and of the funds for the overall program. In this vein, I feel strongly that the public-private partnership is the way forward in defeating malaria.”

“While we provide Coartem at cost,” Vasella notes, “our efforts would be in vain without the Global Fund’s financial aid allowing governments of malaria endemic countries to purchase the drug. Up to now we have been subsidizing Coartem and do not anticipate making a profit from future sales. But much more needs to be done. New partners and donors must be encouraged to join the fight”.