Commercial formulation development of DSM265
  • Awarded Year
    2015
  • Awarded Amount
    $1,905,341
  • Disease
    Malaria
  • Intervention
    Drug
  • Development Stage
    Clinical Phase2
  • Collaboration Partners
    Takeda Pharmaceutical Company Limited, Medicines for Malaria Venture (MMV)

Introduction and Background of the Project

DSM265 is an approved clinical candidate in the portfolio of Medicines for Malaria Venture. DSM265 is a novel, selective inhibitor of Plasmodium dihydroorotate dehydrogenase (DHODH) and has entered a Phase IIa Proof of Concept study in patients with uncomplicated P. falciparum or P. vivax malaria in Peru. The compound has great potential as an antimalarial for treatment and chemoprophylaxis.

 

This project proposal is a supplement grant to GHIT in addition to current funding for the project “Development of DSM265 as long acting antimalarial compound” to allow the development of a commercial formulation of DSM265. The proposal builds on the initial results of our formulation development work and shall provide key elements for full development of a DSM265 drug product before initiation of Phase IIb.

How can your partnership (project) address global health challenges?

Despite being an entirely preventable and treatable disease, malaria still places 3.3 billion people at risk in 97 countries, with more than 200 million cases leading to an estimated 584,000 deaths each year. The WHO estimates that 90% of all malaria deaths occur in sub-Saharan Africa, killing globally 453,000 children under five years of age in 2013. That is one child almost every minute.

 

Furthermore, the emergence of resistance to insecticides and malaria medicines currently being used in endemic countries is a growing concern. Parasite resistance to artemisinin – the core compound of ACTs – has been detected in four countries in Southeast Asia: Cambodia, Myanmar, Thailand and Vietnam.

 

The imperative, therefore, is to develop and implement approaches that will eradicate the parasite. In line with this, MMV’s strategy looks both at the short-term ‘low-hanging fruit’, that we can deliver to the market within the next 5 years to support elimination efforts, and projects that lay the groundwork for ‘game-changing’ next-generation medicines to support eradication. The top priorities for the development of novel malaria treatments are to provide the next generation of medicines – a single exposure radical cure and prophylaxis (abbreviated to SERCaP). A SERCaP product would transform malaria treatment and could form the base of an eradication agenda based on mass drug administration. Target Compound Profile (TCP)-two defines long duration compounds that address residual parasitemia, to protect the fast-acting molecule against development of resistance and to provide, in the ideal case, post-treatment prophylaxis.

 

The DSM265 project perfectly fits into TCP2; its plasma pharmacokinetics could support a long pharmacologically effective half-life. Recently, DSM265 entered Proof-Of-Concept studies in patients with P. falciparum or P. vivax malaria. Results on liver stage parasites in vitro also suggest a fit for TCP4. Combined with the long half-life, this makes this drug a very exciting candidate of a new generation of chemo-preventive agents and potentially an adequate use in low transmission blocking areas of disease endemic countries. 

What sort of innovation are you bringing in your project?

This project aims at developing a commercial formulation of DSM265 prior to phase IIb clinical trials allowing cost effective clinical trial designs (i.e. seamless phase IIb /III). 

Role and Responsibility of Each Partner

Takeda will be responsible for consulting within the project team on Chemistry, Manufacturing and Control and scientific aspects. The project will be conducted by a team comprising scientists from MMV and Takeda. This project team will be responsible for all the activities.

 

MMV as designated development partner for this proposal is responsible for delivering the work plan to the agreed timeline and budget, in addition to required GHIT reporting. MMV will lead the project, manage the project and co-ordinate the activities. The work will be conducted in collaboration between MMV, Takeda and a Contract Research Organization.

Others (including references if necessary)

WHO World Malaria Report 2014

Phillips et.al.; A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria. Science Translational Medicine. 2015 Jul 15;7(296)