- Target disease: Filarial diseases
- Main partners (since project start): Abbvie, USA; AWOL, UK; Liverpool School of Hygiene & Tropical Medicine, UK; University Hospital of Bonn, Institute of Medical Microbiology, Immunology and Parasitology, Germany; University of Liverpool, UK.
- Start date: March 2015
- Funding (since project start): Bill & Melinda Gates Foundation, USA; Department for International Development (DFID), UK; Federal Ministry of Education and Research (BMBF through KfW), Germany; USAID, USA.
The filaria causing river blindness are dependent on the worm-symbiont Wolbachia bacteria for growth, development, reproduction, and survival; elimination of the symbiont with antibiotic drugs therefore has the potential to lead to worm death, delivering a new and practical solution for treating and eliminating this deadly disease. TylAMac, or ABBV-4083, is a derivative of tylosin, a veterinary antibiotic that targets Wolbachia, and was identified by a screening of anti-infective compounds led by AbbVie and the anti-Wolbachia consortium A-WOL at the Liverpool School of Tropical Medicine. The compound is currently in clinical development for the treatment of filarial diseases. TylAMac 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.
The Phase I study, that took place at AbbVie’s Clinical Pharmacology Research Unit, was completed in 2018; the results support progression to Phase II. 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.
Toxicology studies were completed in 2017, and an oral formulation was developed. In December, 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, conducted at at AbbVie’s Clinical Pharmacology Research Unit in Chicago, US is expected to be completed in 2018.
Preliminary safety and toxicology profiling of this compound suggests a favourable safety profile. Upon completion of toxicology studies and the development of an oral formulation, a Phase l study will be conducted in 2017. The aim will be to assess the safety, tolerability, and pharmacokinetics of ABBV-4083.
Last update: August 2019