patients

FILARIAL DISEASES
R&D MODEL & PORTFOLIO
TRANSLATION
Macrofilaricide 2
PROJECT START: March 2015
OVERALL OBJECTIVE: Develop a macrofilaricide effective
against worm-symbiotic Wolbachia bacteria
Two derivatives of a veterinary antibiotic, which target
the worm-symbiont Wolbachia bacterium, are currently
in development for treatment of filarial diseases. These
compounds can be delivered orally, induce a robust anti-
Wolbachia effect in several in vivo models, demonstrate clear
superiority over doxycycline, and are effective after a shorter
dosing regimen. Preliminary safety and toxicology profiling of
these compounds carried out in 2015 suggests a favourable
safety profile. Upon successful completion of the necessary
toxicology studies, expected in 2016, and development of an
oral formulation, a Phase I single rising dose study in healthy
human volunteers will be performed to determine the safety,
tolerability, maximum tolerated dose, and pharmacokinetics
of single oral doses of the selected compound. If appropriate
pharmacokinetic characteristics are demonstrated and are
suggestive of sufficient therapeutic margins, the safety,
tolerability, and pharmacokinetics of multiple ascending
doses of an oral formulation of the compound will be
determined. To demonstrate proof of concept for filarial
disease, a Phase Ib programme will be conducted in patients.
This programme will be designed to provide data on which
a collective decision can be made to proceed into Phase II
studies in patients with either onchocerciasis or lymphatic
filariasis.
MAIN PARTNERS: AbbVie, USA; Liverpool School of Tropical
Medicine, UK
Emodepside
PROJECT START: March 2013
OVERALL OBJECTIVE: Develop emodepside as a new
macrofilaricidal treatment for patients suffering from
onchocerciasis
2015 OBJECTIVES:
• Complete pre-clinical package for first-in-human study
• Progress emodepside into first-in-human study
Emodepside is a semi-synthetic product (originated by
Astellas and out-licensed to Bayer for animal and human
use); its precursor is synthesized by a fungus living in the
leaves of Camellia japonica. It is a potent antihelminthic drug
used in combination with praziquantel (as Profender ® ) and in
combination with toltrazuril (as Procox ® ) for the treatment of
parasitic worms in cats and dogs. DNDi and Bayer Pharma
AG are jointly developing emodepside for the treatment of
onchocerciasis patients. DNDi will be responsible for the
pre-clinical and clinical development of emodepside and
Bayer for the pharmaceutical development, manufacturing,
registration, and supply of the drug at the lowest sustainable
price. The pre-clinical package to start Phase I studies was
completed and recruitment into a single-ascending dose
study was initiated in December 2015.
MAIN PARTNER: Bayer HealthCare, Germany
Filling knowledge gaps
As is frequently the case with neglected diseases, there are
a number of knowledge gaps. DNDi partners are carrying out
modelling studies aiming to quantify and characterize the
future needs of patients suffering from onchocerciasis and
lymphatic filariasis, and to provide information on the size
and profile of target populations for the new treatments in
development. There is also a need for reliable biomarkers
of disease evolution which can assess the effect of new
treatments as an alternative to existing invasive skin biopsies
and nodulectomies. A new medical optical imaging technique
is being evaluated, which aims to find an optical signature of
live versus dead O. volvulus worms in subcutaneous nodules.
PARTNERS: Erasmus University, the Netherlands; CEA-LETI (1),
France; REFODTE, Cameroon; Institut de Recherche pour le
Développement, France.
(1) LETI a French state-owned research entity, (Commissariat à
l’énergie atomique et aux énergies alternatives (CEA), Laboratoire
d’Électronique et de Technologies de l’Information (LETI).
DNDi Annual Report 2015 › 43