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New Zealand malaria drug passes first stage trials

Media Release

17 February 2012

An anti-malarial compound first synthesized at IRL, BCX4945, has successfully passed the first stage of a preclinical efficacy study.

A mosquito-borne infectious disease that results from red-blood cells being overrun by parasites of the Plasmodium genus, Malaria kills about one million people annually.

“About 90 per cent of all deaths worldwide are caused by the protozoan parasite Plasmodium falciparum,” says Principal Scientist Dr Gary Evans from IRL’s Carbohydrate Chemistry group.

“Early efficacy trials have shown that BCX4945 clears the parasite responsible for malaria within seven days,” he says.

“The project was led by Professor Vern Schramm from the Albert Einstein College of Medicine, a long-time collaborator with the IRL Carbohydrate Chemistry group,” Dr Evans says.

At present there is no long-term vaccine for malaria and although different treatments are available, the parasite often becomes resistant or immune to them.

Malaria is transmitted by mosquitoes and efforts to fight it have historically focused on preventative measures such as draining stagnant water and providing people with mosquito netting.

People infected by P. falciparum will often suffer from severe shivering every 36-48 hours. Coma - and death - can result if the parasite goes untreated, with brain damage due to anaemia common among children.

Children and pregnant women are particularly vulnerable to the disease.

The positive trial results give hope that BCX4945 might become a valuable addition to the existing arsenal currently used in the treatment of the disease.

“The parasite is relatively unusual in that it’s a purine auxotroph, meaning that it sources organic compounds known as purines from its host,” Dr Evans says.

The new drug blocks the enzyme used by the parasite to harvest these compounds and so the parasite can no longer multiply and overwhelm the host's immune system.

“It’s a numbers game - they build millions of themselves," Dr Evans says. "If you keep that number small then the host immune system can simply manage the infection.”

“The initial discovery of BCX4945 was achieved by IRL’s Carbohydrate Chemistry group but further development has been an excellent example of scientific and industrial collaboration.”

Early aspects of the study were funded by Medicines for Malaria Venture (MMV), a non-profit foundation created to discover, develop and deliver new, affordable anti-malarial drugs through effective public-private partnerships.

Professor Schramm has managed the overall project, which is being carried out by a multi-disciplinary team from the following organisations:

• IRL Carbohydrate Chemistry Group, Lower Hutt, New Zealand
• Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States
• Tropical Medicine Research, Malaria Drug and Vaccine Evaluation Center, Gorgas Memorial Institute of Health Studies, Panama City, Panama
• Waters Corporation, Parsippany, NJ, United States
• BioCryst Pharmaceuticals, Inc, Birmingham, AL, United States

“We licensed BCX4945 to BioCryst Pharmaceuticals, Inc. in the USA, but our main point of contact is the Albert Einstein College of Medicine of Yeshiva University," Dr Evans says.

The drug's progress is being followed closely by New Zealand's burgeoning pharmaceutical industry, including New Zealand Pharmaceuticals Ltd (NZP), who possess the capability to manufacture the drug's active pharmaceutical ingredient.

"We look forward to watching the clinical progress of BCX4945 and hope to manufacture it as our contribution to the future of this malaria drug,” NZP Ltd Business Development Manager Selwyn Yorke says.

While the results are positive there is still much to be done before the drug can be used in the field, possibly as part of a combination therapy, for the treatment of malaria.

“The other drug candidates we are involved with have spent as many as 10 years in pre-clinical and clinical trials,” Dr Evans says.


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