GSK and MMV recently received data from two Phase III clinical trials assessing use of the artemisinin-based combination therapy Dacart, a fixed-dose combination of chlorproguanil, dapsone and artesunate, currently in clinical development.
The first trial was primarily designed to establish the efficacy of Dacart versus Coartem™ (artemetherâlumefantrine), currently the first-line antimalarial therapy in many endemic countries. The study, in 1372 patients showed statistical non-inferiority with 94% efficacy at 28 days for Dacart and 97% for Coartem. However, although the efficacy of Dacart was in line with expectations, the reduction in haemoglobin concentration observed in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency taking Dacart, was greater than that of Coartem.
A reduction in haemoglobin can lead to anaemia which, in some severe incidences, may require treatment with blood transfusions. G6PD deficiency is a hereditary enzyme disorder which is estimated to affect 10-25% of the population in sub-Saharan Africa. The G6PD enzyme is important for the normal functioning of red blood cells and deficiency of the enzyme in certain individuals can only be detected using a blood test which is often not a practical option in Africa.
The second trial, in 892 patients, was designed to establish the efficacy of Dacart versus Lapdap (chlorproguanil and dapsone), another anti-malarial product GSK developed in a partnership including the World Health Organisation (WHO) and the UK's Department for International Development (DFID). Significant reductions in haemoglobin levels of patients with G6PD deficiency were observed for both Dacart and Lapdap in this trial.
On the basis of these data, GSK and MMV have decided to terminate further development of Dacart. GSK has also commenced a product recall process at pharmacy level in Kenya, for Lapdap, this being the only market with recent sales of the product.
Dr Lynn Marks, SVP of the GSK Medicines Development Centre for Infectious Diseases said: "This news is disappointing and highlights the high-risk, complex nature of pharmaceutical research and development. However, GSK remains committed to working with partners such as MMV to seek solutions for patients suffering from this devastating disease."
"Our goal has always been to develop the best and most appropriate antimalarials for developing countries," stated Dr Tim Wells, Chief Scientific Officer of MMV. "The tough decision to halt the development of Dacart was driven by quality data demonstrating that the MMV-GSK partnership puts patients first. We are proud of the professionalism and dedication of the project team, investigators and their teams and grateful to all the patients who participated in the study."
Dr Arata Kochi, Director Global Malaria Programme, WHO commented: "GSK has acted with responsibility in taking action to withdraw Lapdap from the market and to discontinue any further development of medicines based on this compound. The World Health Organisation emphasizes the critical need and urgency today, for new medicines and interventions to combat malaria, whilst at the same time calling for investigators and industry to act responsibly. We therefore, commend the display of integrity on the part of GSK an important pharmaceutical collaborator, and its partner organisation MMV, and welcome this spirit of honesty and transparency as a foundation for future collaboration for the development of products to fight malaria."
Both Phase III trials were conducted in Africa with African principal investigators and centralised laboratory work completed to high quality in competent African laboratories.
Comprehensive, high quality data on the changes that occurred to patients' haemaglobin profile during use of both Dacart and Lapdap in malaria patients will be useful for the public health and malaria community. GSK and MMV are committed to publishing these important data in due course.
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Medicines for Malaria Venture (MMV) is a non-profit organisation dedicated to reducing the burden of malaria in disease-endemic countries by discovering, developing and delivering safe, effective, and affordable antimalarial drugs through effective public-private partnerships. After seven years of operation, MMV is managing the largest-ever portfolio of malaria drug research with nearly 40 projects in different stages of drug research and development. MMV's goal is to register at least one new antimalarial before 2010 and maintain a sustainable pipeline of antimalarials to meet the needs of the 3.2 billion people at risk from this deadly disease. For further information please consult http://www.mmv.org.