Development of AWZ1066S, A Small Molecule anti-Wolbachia Candidate Macrofilaricide Drug
Project Completed

Introduction and Background of the Project


Lymphatic filariasis (elephantiasis) and onchocerciasis (river blindness) are two neglected tropical diseases that are caused by parasitic worms.  These diseases affect more than 150 million people globally.  The international community agrees that these diseases should and could be eradicated with the correct tools and there are ongoing mass drug administration campaigns underway to achieve this goal.  However, in the absence of a drug that can kill adult parasites, current programmes require many years of annual (or greater) rounds of drug administration to large populations in the rural communities blighted by these diseases.  We have demonstrated that adult worms can be killed by eliminating a bacterium that they contain called Wolbachia

This approach has the potential to significantly reduce the timescale of eradication programmes, to provide alternatives to current drugs and to deliver an additional tool that can be used in areas where current approaches are failing, or cannot be deployed. The antibiotic doxycycline works in this way and proof of concept has already been proven in human field trials.  Results were excellent but required 4 to 6 weeks of daily treatment.  Also this drug cannot be used in children and pregnant women, who represent a large proportion of the target population.    

We have identified a new drug candidate that acts more quickly and efficiently than doxycycline and has been shown to be safe in pre-clinical testing.


Project objective

The objective of this project is to continue the development of this drug candidate further by completing a series of Phase I clinical trials which will assess safety in humans. This is an essential step in the development of a new drugs and brings us closer to a new treatment for these diseases.


Project design

The project will involve:

  •        the manufacture of sufficient quantity of the drug candidate to the required quality,
  •        application and granting of permission to conduct the clinical trial 
  •        completion of the trial in line with international requirement for the licencing of new drugs.

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

Parasitic worm diseases inflict serious public health problems throughout tropical communities. Global programs for control and elimination have been developed to provide sustained delivery of drugs to affected communities in order to interrupt transmission of disease and ultimately eliminate this public health burden. Existing drugs principally target the young worms and not the adult worms.  This means that sustained and prolonged delivery with high treatment coverage to endemic communities is required in order to break the transmission cycle of the long-lived (onchocerciasis 10-14 years, Lymphatic Filariasis 5-8 years) adult worms. Seventeen countries in hard-to-reach areas, including post-conflict countries, have still not implemented mass drug administration against Lymphatic Filariasis 12 years after the Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched. In some of these countries, the growing evidence for resistance to the current drug ivermectin and safety constraints in areas co-endemic with a similar infection called Loa loa has re-focused the need and urgency for new safe drugs that kill adult worms and regimes to achieve control programme goals within existing timeframes.

Our approach of killing the bacteria within the worms means that adult worms are killed.  This leads to better therapeutic outcomes compared to all current treatments, with the added benefit of substantial improvements in disease progression. The use of doxycycline to kill adult worms has been established as proof-of-concept in an extensive series of field trials, but its widespread use in community-based control is constrained by the logistics of a relatively lengthy course of treatment (4-6 weeks) and contraindications in children under eight years and pregnancy. These barriers highlight the need for a new drug to overcome these problems and the current drug candidate, AWZ1066S provides a unique opportunity to make a large contribution to communities affected by these diseases.

What sort of innovation are you bringing in your project?

The approach of killing the parasitic worm by targeting the essential bacteria within the worm is a totally unique approach and one that offers many advantages over drugs that target worms directly. Proof-of-concept clinical trials have already shown that this alternative approach works and can reduce elimination timeframes significantly.  Our drug candidate also has the potential to be used in the whole population, including children and pregnant women.

Role and Responsibility of Each Partner

The Liverpool School of Tropical Medicine (LSTM) is the designated coordination partner for the project and is responsible for the overall management of the project and will be principle sponsor of the Phase I clinical trial.  LSTM has a wealth of experience of running similar programs, developing drugs in collaboration with academic and industrial partners. In the role as coordinator, the LSTM team, led by Prof Ward who has over 30 years experiences in research and development of new drugs for the treatments of NTDs, will liaise with all partners and the funder GHIT.

Eisai provides industry standard preclinical and clinical development expertise as we progress to the clinical development stage. The Eisai team, led by Dr Gusovsky, who has recently completed two stages of clinical development of an antimalarial candidate funded by GHIT, is responsible for coordinating the Eisai teams from the different sites. Eisai’s Research facility will manufacture and test the material for use in the clinical trial.  Eisai will work collaboratively with LSTM on the Regulatory and Clinical Strategy.

The University of Liverpool teams, one led by Professor Paul O’Neill will take the responsibility of carrying out the mechanism of action/resistance studies and the other one led by Dr Richard FitzGerald, the Director of the Royal Liverpool and Broadgreen, Clinical Research Facility (CRF) and a qualified first-in-human principal investigator, will lead the proposed Phase I clinical trial.

Others (including references if necessary)