DNDi aims to develop a treatment for visceral leishmaniasis that is active against resistant strains and is suitable for all populations, including pregnant women and immune-compromised/-suppressed patients, with a maximum duration of ten days for once-daily oral treatment or three intramuscular injections.

Target product profile for primary visceral leishmaniasis

IdealAcceptable
Target populationPatients with visceral leishmaniasis

Immunocompetent and immunosuppressed
Patients with visceral leishmaniasis

Immunocompetent
Target speciesAll species

Active against resistant strains
L. donavani

Active against resistant strains
Geographic distributionAll areasEither India or Africa
Efficacy >95% >90%
Safety/tolerabilityNo adverse events requiring monitoring1 monitoring visit at mid-/end-point
ContraindicationsNonePregnancy/lactation
Drug-drug interactionsNone – compatible for combination therapyNone for concomitant therapies for malaria, TB, and HIV
FormulationOral/ intramuscularOral/ intramuscular
Treatment regimenOral: 1/day for 10 days
Intramuscular: 3 shots over 10 days
Bid for <10 days oral
>3 intramuscular injections over 10 days
Stability3 years in climatic zone IVStable under conditions that can be reasonably achieved in the target region (>2 years)
Cost<USD 10/course<USD 80/course

DNDi aims to develop an all-oral one-week combination treatment for visceral leishmaniasis that is active against resistant strains and suitable for all populations, including pregnant women and immunocompromised/-suppressed patients.

Target product profile for visceral leishmaniasis combination therapies

Ideal Acceptable
Target populationPatients with visceral leishmaniasis and PKDL

Immunocompetent and immunosuppressed
Patients with primary visceral leishmaniasis

Immunocompetent
Target speciesAll species

Active against resistant strains
L. donavani

Active against resistant strains
Geographic distributionAll areasEastern Africa
Efficacy≥95%≥90%
Safety/tolerabilityNo adverse events (AEs) requiring monitoring1 monitoring visit at mid-/end-point OR baseline assessment to exclude high-risk groups (dependent on the profile of the drug) and self-report if AEs
ContraindicationsNonePregnancy/lactation
Drug-drug interactionsNo interactions between the drugs to be combined for visceral leishmaniasis treatment, or with those used for other common co-morbidities (malaria, TB, HIV)No interactions between the drugs to be combined for visceral leishmaniasis treatment
FormulationOral/oralOral/ intramuscular injections
Intravenous injections could be acceptable
Treatment regimenSingle dose treatment or fixed-dose combination tablet/paediatric formulation up to 7 daysCurrently existing drugs: twice daily for ≤28 days oral; and intramuscular injections ≤14 days
Stability3 years in climatic zone IV2 years in climatic zone IV
CostTo be definedTo be defined

DNDi aims to develop an oral, maximum four-week daily treatment for PKDL in all patients and all regions, including pregnant women and immunocompromised patients (especially those co-infected with HIV).

Target product profile for post-kala-azar dermal leishmaniasis

IdealAcceptable
Target populationAll patients with PKDL

Pregnant women, but delay treatment after delivery

Immunocompromised patients (especially HIV co-infected patients)
All in South Asia persistent (>6 months) or grade 3 PKDL in Eastern Africa + grade 2 severe presentation

No studies done in pregnant women

Regimen adapted for immunocompromised patients (especially HIV co-infected patients)

Immunocompetent
Target speciesL. donavaniL. donavani
Geographic distributionAll areasAdapted by region (Asia or Africa)
Efficacy

Complete clinical cure:
– 100% disappearance of papules or nodules by 12 weeks
– 80% improvement in macular lesions with re-pigmentation
>90% efficacy

[Pharmacokinetics of new chemical entities: penetration in the skin should also favour development for PKDL]
>80% efficacy
Safety/tolerabilityNo adverse events (AEs) requiring monitoring

Well tolerated

All AEs ≤ grade 1
No major safety concerns
Acceptable for patient to come for one follow-up visit during treatment

Well tolerated in >90% of patients treated
Systemic AE > grade 2 in < 5%
No treatment-induced mortality
No irreversible AEs
ContraindicationsNoneAssessed by qualified person at primary health care/district hospital level, as per local context
FormulationOralOral or combination oral-parenteral
Treatment regimen≤4 weeks treatment once per dayTwice daily for up to 6 weeks oral (regardless of PKDL presentation)
Up to 2 weeks if intramuscular injections
Up to 7 injections if intravenous injections
Stability≥3 years in climatic zone IV2 years in 4-8°C
Stable under storage at <30° C in case of self-administered
Cost<EUR 60<EUR 100 for treatment (Ministry of Health)