R&D Portfolio Update February 2019: DNDi Filarial diseases programme

 

DNDi aims to deliver:

  • A new oral, short-course macrofilaricide or long-term sterilizing treatment, with potential application to treat both onchocerciasis and lymphatic filariasis.

 

Man with river blindness standing in front of his houseDNDi aims to deliver a new, oral, short-course macrofilaricide treatment for river blindness, to offer patients a cure that kills adult worms and allows for treatment in regions co-endemic for Loa loa. DNDi now has a diverse portfolio of potential macrofilaricides with different modes of action:

 

Research

Discovery

One project in the discovery phase:

 

  • Macro-filaricide 3: Lead optimisation of a novel class of compounds with macrofilaricidal profiles is on-going with the aim to select a candidate for pre-clinical development in 2019.

 

Translation

Translation

Three projects in the translation phase:

 

  • Emodepside1: Originating from the Japanese pharmaceutical company Astellas, emodepside has been developed and is currently commercialized by Bayer Animal Health as an anti-helminthic veterinary drug for cats and dogs. DNDi has a collaboration agreement with Bayer to jointly develop emodepside for the treatment of onchocerciasis. First-in-human studies for emodepside in healthy volunteers have successfully been completed, both a single ascending dose study completed in 2017 and a multiple ascending dose study completed at the end of 2018. As a next step, DNDi plans to run a Phase II “proof-of-concept” clinical trial in sub-Saharan Africa, investigating the safety and efficacy of the drug in people living with onchocerciasis. 
  • OxfendazoleOxfendazole is currently under development for the treatment of neurocysticercosis and trichuriasis. Based on highly encouraging pre-clinical efficacy data, DNDi is exploring the possibility of repurposing oxfendazole as a macrofilaricidal treatment for filarial indications. DNDi intends to initiate a first-in-human trial and complete formulation development.

  • ABBV-4083: ABBV-4083 is a derivative of tylosin, a veterinary antibiotic that targets the worm-symbiont Wolbachia. The compound is currently in clinical development for the treatment of filarial diseases. ABBV-4083 is orally available, induces a robust anti-Wolbachia effect in several in vivo models, demonstrates clear superiority over doxycycline, and is effective after a shorter dosing regimen. Preliminary safety and toxicology profiling of this compound suggest a favourable safety profile.

  • Toxicology studies were completed in 2017 and an oral formulation was developed. In December 2017, AbbVie began the first human trial of ABBV-4083 to test the drug’s safety in healthy volunteers and assist in the selection of doses for future trials. This Phase I study took place at AbbVie’s Clinical Pharmacology Research Unit and was completed in 2018; the results support progression to Phase II.

 


[1] A collaboration agreement was signed between Bayer AG and DNDi in December 2014 – DNDi is responsible for the clinical development of emodepside and Bayer for the pre-clinical and pharmaceutical development as well as for registration, manufacturing, and distribution of the drug. Bayer AG provides the active ingredient emodepside to DNDi. Emodepside originates from the Japanese pharmaceutical company Astellas and has been developed by Bayer’s HealthCare’s Animal Health division for veterinary use. Astellas has granted Bayer AG the rights to develop emodepside along these lines.

 

Photo credit: Neil Brandvold-DNDi