patients

R&D MODEL & PORTFOLIO
LEISHMANIASIS
DEVELOPMENT
IMPLEMENTATION
New VL treatments
for Latin America
PROJECT START: February 2011
OVERALL OBJECTIVE: Assess the efficacy and safety of
amphotericin B deoxycholate, AmBisome ® , and AmBisome ®
combined with Glucantime ® , as compared to the first-line
treatment, Glucantime ® , for the treatment of VL patients in Brazil
2015 OBJECTIVE: Complete VL trial
378 patients
recruited
at 5 sites
(2 active in 2015)
More than 95% of VL cases in Latin
America occur in Brazil, and most
of them are children. In 2013, Brazil
reported 3,253 new cases with a
fatality rate of 6.7%. DNDi is supporting
the implementation of a Phase IV clinical trial, sponsored
by the Brazilian Ministry of Health, to assess current
treatments used for VL in Brazil (Glucantime ® , AmBisome ® ,
and amphotericin B as monotherapies, and an AmBisome ® /
Glucantime ® combination proposed by DNDi). In 2014, patient
recruitment was stopped based on the interim analysis of 50%
of the recruited patients, and the five trial sites concluded six
months follow-up of the 378 patients enrolled in the study.
Data management and sites close-out were finalized in 2015
and study results show that, although there is no statistically
significant difference in efficacy between treatment arms,
AmBisome ® monotherapy shows a statistically better safety
profile in terms of frequency and severity of adverse events,
and early treatment suspension due to toxicity. These results,
associated with a shorter administration time, suggest that
AmBisome ® monotherapy would be a more adequate first
line treatment of VL in Brazil and in Latin America. All final
results will be published in 2016. Follow-up discussions will
be held with the Brazilian Ministry of Health and PAHO in
2016 for evidence-based policy changes in the treatment of VL
patients in Brazil, and to discuss plans for further studies to
improve efficacy with good safety profile for treatment of VL
in Brazil. The Ministry of Health already changed treatment
recommendations in 2013, expanding the use of AmBisome ®
monotherapy as a second-line treatment, based on interim
safety data provided by the trial.
SSG&PM Sodium Stibogluconate/
Paromomycin Combination
Therapy
PROJECT START: April 2011
OVERALL OBJECTIVE: Include SSG&PM as the new first
line treatment for primary VL in the national guidelines of
countries in the region, disseminate results to the region’s VL
stakeholders and update registration status of SSG&PM
2015 OBJECTIVES: Renew retention of SSG&PM in the register
for Kenya and Uganda and register SSG and PM in Ethiopia and
Sudan
More than
10,000 patients
In 2010, DNDi and LEAP successfully
showed that the combination of SSG
and PM (17 days) was as efficacious
treated
as SSG monotherapy (30 days); this shorter course lessens
the burden on patients and health systems, and is more cost
effective. WHO recommended SSG&PM combination as first
line treatment for primary VL in Eastern Africa in March of
the same year, and a large Pharmacovigilance (PV) study was
implemented in Sudan, Ethiopia, Uganda, and Kenya between
April 2011 and May 2014. The PV study results showed a 95%
cure rate at the end of treatment with the SSG&PM therapy
with no new safety concerns.
SSG&PM is recommended as first-line treatment for VL in
Sudan, Ethiopia, South Sudan, Somalia, and Kenya. SSG&PM
has been included in the national guidelines of Sudan, South
Sudan, Ethiopia, Somalia, and Kenya, and the guidelines are
under review in Uganda. PM is registered in Uganda (2011)
and Kenya (2013), and is in the process of registration in
Sudan and Ethiopia.
MAIN PARTNERS: Ministries of Health of Uganda, Sudan, Kenya, and
Ethiopia; Institute of Endemic Disease (IEND), Khartoum University,
Sudan; Kenya Medical Research Institute (KEMRI), Kenya; Gondar
University Hospital, Ethiopia; Addis Ababa University, Ethiopia;
Arba Minch Hospital, Ethiopia; Makerere University, Uganda;
Amudat Hospital, Uganda; LEAP; Médecins Sans Frontières (MSF),
Switzerland and Holland; London School of Hygiene and Tropical
Medicine (LSHTM), UK; IDA Foundation, The Netherlands
PARTNERS: BRAZIL: Rene Rachou Research Center – Fiocruz-MG,
Belo Horizonte; Paediatric Hospital Joao Paulo II – FHEMIG, Belo
Horizonte; Brasilia University; Montes Claros State University;
Piaui Federal University, Teresina; Sergipe Federal University,
Aracaju; Leishmaniasis Control Programme/Ministry of Health;
Universidade Estadual do Rio de Janeiro; Hospital Sao José de
Doencas Infecciosas, Fortaleza
34 › DNDi Annual Report 2015