Next generation Malaria drug shows promise
pharmafile | September 6, 2010 | News story | Research and Development | malaria
A Novartis-led collaboration has discovered a novel anti-malarial candidate that could become the first new treatment for the disease in over 30 years.
Scientists at the Novartis Institute for Tropical Diseases worked with researchers from the Genomics Institute of the Novartis Research Foundation, the Swiss Tropical and Public Health Institute and The Scripps Research Institute on the discovery.
“Malaria remains a scourge,” said Mark Fishman, president, Novartis Institutes for BioMedical Research. “The parasite has demonstrated a frustrating ability to outwit new medicines, from quinine to today’s unsettling increased tolerance to artemisinin derivatives.
“We are delighted that our scientists could provide this potential new malaria therapy, based on an unprecedented chemical structure and directed to a novel target.”
Spiroindolone NITD609 has been shown effective in pre-clinical trials against both strains of the malaria parasite, Plasmodium (P.) falciparum and P. vivax, in the American journal Science.
Its novel mechanism of action has the potential to rapidly clear the potent Plasmodium infection – the parasite responsible for malaria – with only a single oral dose.
In the trials NITD609 rapidly cleared infection in a malaria mouse model and showed “pharmacological properties compatible with a once-daily dosing regimen”.
The drug’s development is currently in an early stage, but Novartis expect clinical trials to begin later this year.
Additional funding for the project was provided by the Wellcome Trust, Medicines for Malaria Venture (MMV) and the Agency for Science, Technology and Research (A*STAR), as well as the US and Singapore governments.
Rick Davis, business development manager at the Wellcome Trust, said: “This study illustrates how philanthropic organisations can support pharmaceutical partners undertaking innovative drug discovery for neglected diseases.
“A single dose cure would go a long way to addressing the unmet medical need in malaria, and we look forward to seeing how this compound performs in clinical trials.”
Despite significant advances in Plasmodium genome biology, the identification and validation of new drug targets has proven challenging.
Using a novel Plasmodium whole-cell assay, the Novartis-led collaborators were able to utilise Novartis’s archive of 12,000 different chemicals to find the new candidate.
This discovery process took less than three years – “a turbocharged pace,” according to Tim Wells, chief scientist at medicines for malaria venture, writing in the Science article.
The World Health Organization (WHO) says there are about 243 million cases of malaria each year, causing an estimated 863,000 deaths, mostly among young children in Africa.
There have been a number of malaria treatments over the years, including quinine and artemisinin derivatives. But both types have fallen prey to the way parasites and their hosts evolve, leading them to become increasingly resistant to such drugs.
Any new treatment for malaria will have to meet this fundamental problem as the sheer number of mosquitoes and their internal parasites make drug resistance almost inevitable, even in the most effective of treatments.
GlaxoSmithKline is currently undertaking late stage trials in its experimental vaccine Mosquirix and expects to see results by 2011. The UK firm says that if it proves effective, it will seek regulatory approval for the vaccine in 2012.
Ben Adams
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