Target product profile for visceral leishmaniasis

Visceral leishmaniasis

Target product profile for visceral leishmaniasis

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

	Ideal	Acceptable
Target population	Patients with visceral leishmaniasis Immunocompetent and immunosuppressed	Patients with visceral leishmaniasis Immunocompetent
Target species	All species Active against resistant strains	L. donovani Active against resistant strains
Geographic distribution	All areas	Either India or Africa
Efficacy	>95%	>90%
Safety/tolerability	No adverse events requiring monitoring	1 monitoring visit at mid-/end-point
Contraindications	None	Pregnancy/lactation
Drug-drug interactions	None – compatible for combination therapy	None for concomitant therapies for malaria, TB, and HIV
Formulation	Oral/ intramuscular	Oral/ intramuscular
Treatment regimen	Oral: 1/day for 10 days Intramuscular: 3 shots over 10 days	Bid for <10 days oral >3 intramuscular injections over 10 days
Stability	3 years in climatic zone IV	Stable 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 population	Patients with visceral leishmaniasis and PKDL Immunocompetent and immunosuppressed	Patients with primary visceral leishmaniasis Immunocompetent
Target species	All species Active against resistant strains	L. donovani Active against resistant strains
Geographic distribution	All areas	Eastern Africa
Efficacy	≥95%	≥90%
Safety/tolerability	No adverse events (AEs) requiring monitoring	1 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
Contraindications	None	Pregnancy/lactation
Drug-drug interactions	No 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
Formulation	Oral/oral	Oral/ intramuscular injections Intravenous injections could be acceptable
Treatment regimen	Single dose treatment or fixed-dose combination tablet/paediatric formulation up to 7 days	Currently existing drugs: twice daily for ≤28 days oral; and intramuscular injections ≤14 days
Stability	3 years in climatic zone IV	2 years in climatic zone IV
Cost	To be defined	To 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

	Ideal	Acceptable
Target population	All 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 species	L. donovani	L. donovani
Geographic distribution	All areas	Adapted 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/tolerability	No 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
Contraindications	None	Assessed by qualified person at primary health care/district hospital level, as per local context
Formulation	Oral	Oral or combination oral-parenteral
Treatment regimen	≤4 weeks treatment once per day	Twice 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 IV	2 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)

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