Malaria

Tafoxiparin in Phase I clinical trials for the treatment of severe malaria
Dilafor has produced a range of heparin analogues with low anticoagulant activity during the selection of a candidate drug (CD) for the treatment of severe malaria. These products have been tested in animal models mimicking the clinical manifestations of severe malaria. The selected CD, sevuparin, has been produced according to c-GMP and will be developed as a registered pharmaceutical product. The first study of sevuparin in man was initiated in May 2009 and completed in September 2009, following successful safety and toxicology studies. A Phase II Proof of Concept trial is planned for Q II, 2011.

Improved knowledge of disease mechanisms allows novel heparin treatments
Heparin has been used as an adjunct treatment of severe malaria. Although this treatment has been successful in the majority of cases, the use of heparin was discontinued due to the occurrence of serious side effects such as intracranial bleeding. Knowledge of the pathology of malaria and the underlying mechanisms leading to severe disease has greatly increased in the last 15 years and new findings have created new possibilities for treatment. The anti-malaria drugs available today are all directed toward the parasite itself. Sevuparin, in contrast, is directed at the invasive mechanism used by the parasite and is the first drug of its kind.
Sevuparin inhibits the invasion of red blood cells (RBC) by the parasite and dissolves aggregates of infected RBC, two important phenomena during severe malaria. Sevuparin potency was tested in vitro and in rats and monkeys. During preclinical evaluation, sevuparin was analyzed in field studies in Cameroon where positive results were achieved with patient samples tested in models.

A new malaria treatment is urgently needed
An estimated 500 million people acquire Plasmodium falciparum malaria each year, of whom approximately 1 to 2 million die. Most deaths are in highly endemic areas of Africa but an estimated 10 000 to 20 000 patients are treated annually in high income countries and in well-equipped hospitals in Europe and North America. More cases are handled in hospital settings in Asia, Australia and Latin America.
The most common clinical manifestation of a malarial infection is a non-specific febrile illness. Severe malaria occurs when P. falciparum infections are complicated by serious organ failures or abnormalities in the blood or metabolism. These manifestations include direct impact on the brain, severe anemia due to hemolysis, pulmonary edema, shock and cardiovascular collapse. Anti-parasitic therapy (e.g. quinine and artemisinine) is given to these patients. No adjunct therapy is currently available.