R&D MODEL & PORTFOLIO
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
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
More than 95% of VL cases in Latin America occur in Brazil, and most recruited of them are children. In 2013, Brazil at 5 sites reported 3,253 new cases with a (2 active in 2015) 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.
for Kenya and Uganda and register SSG and PM in Ethiopia and Sudan
In 2010, DNDi and LEAP successfully More than 10,000 patients showed that the combination of SSG treated and PM (17 days) was as efficacious 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