The filarial worms that cause river blindness are dependent on the worm-symbiont Wolbachia bacteria for growth, development, reproduction, and survival. An antibiotic drug that targets the symbiont would cause the filarial worms to die, offering a new and practical treatment for this deadly disease.

Flubentylosin is a derivative of tylosin, a veterinary antibiotic that targets Wolbachia. The compound was identified through screening of anti-infective compounds led by AbbVie and the anti-Wolbachia consortium A-WOL at the Liverpool School of Tropical Medicine. Flubentylosin is currently in clinical development for the treatment of filarial diseases. Flubentylosin is orally available, induces a robust anti-Wolbachia effect in several in vivo models, demonstrates clear superiority over the current treatment doxycycline, and is effective after a shorter dosing regimen.

First-in-human Phase I studies for flubentylosin in healthy volunteers, including a single ascending dose study, a multiple ascending dose study, and a food effect study, were successfully completed by AbbVie’s Clinical Pharmacology Research Unit. These studies showed that flubentylosin is safe and well tolerated. Next, DNDi will launch a Phase II proof-of-concept study at two recently upgraded clinical trial sites in the Democratic Republic of the Congo (DRC).

Project updates

2021

In 2021, clinical trial sites were established, and staff were trained on all aspects of clinical trial conduct, including good clinical practice based on International Conference on Harmonization (ICH) standards. The Phase II clinical trial testing the safety and efficacy of flubentylosin, previously called TylAMac (ABBV-4083), in patients infected with Onchocerca volvulus was successfully initiated at the trial sites in DRC.  

2020

In 2020, DNDi laid the groundwork for a Phase II proof-of-concept study in the Democratic Republic of Congo. DNDi has upgraded two clinical trial sites, Masi-Manimba in Kwilu province and Kimpese in Bas-Congo province, in preparation for the trial.

2019

Phase I studies have shown that TylAMac is safe and well-tolerated. DNDi is now preparing for a Phase II proof-of-concept study in the Democratic Republic of Congo. A hospital in Masimanimba that has long been one of the principal clinical sites for DNDi’s sleeping sickness studies has already been selected as one site for the study. Entirely renovated by DNDi for sleeping sickness trials, the site is again being upgraded by DNDi, with staff trained to run trials for river blindness. A second hospital will also be selected, and equipment and training provided.

2018

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.

2017

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 AbbVie’s Clinical Pharmacology Research Unit in Chicago, US is expected to be completed in 2018.

2016

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.