R&D Portfolio Update March 2018: DNDi Filarial diseases programme

 

DNDi aims to deliver:

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

 

DNDi 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 potentially killing adult worms:

 

Three patients sitting on a bench

Research

Research

One project in the research phase:

 

  • Macro-filaricide 3: Following a drug repurposing strategy, completion of screening of compounds active against various filarial species identified several hits and leads. One successful compound is a well-known antihelminthic (oxfendazole) that is currently being investigated for feasibility of use in humans. Other screened compounds have been provided by a number of pharmaceutical companies and belong to well-characterized chemical series that have been extensively optimized for other indications. Lead optimization has been undertaken in collaboration with Celgene and identified hits will be further explored. These efforts will continue throughout 2018, with the aim of delivering a pre-clinical candidate for filarial diseases.

 

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. Emodepside entered into healthy volunteer Phase I studies in 2016. The Single Ascending Dose Study was completed in 2017 and the Multiple Ascending Dose Study should be completed in 2018.
  • Oxfendazole: Oxfendazole is currently under development for treatment of neurocysticercosis and trichuris. Taking advantage of preclinical work conducted by JHU, DNDi is exploring the possibility to repurpose oxfendazole as a macrofilaricide treatment for filarial indications.

  • ABBV-4083 (TylaMac)ABBV-4083 is a derivative of Tylosin, a veterinary antibiotic that targets the worm-symbiont Wolbachia. The compound is currently in full pre-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 suggests 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 1 study is expected to be completed in 2018, and is taking place at AbbVie’s Clinical Pharmacology Research Unit.

 


[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