ganaplacide/lumefantrine (KLU156) / Novartis - LARVOL DELTA

PLATINUM: Platform Study to Evaluate the Efficacy and Safety of Anti-malarial Agents in Participants With Uncomplicated Plasmodium Falciparum Malaria (Cohort B2) (clinicaltrials.gov) - P2 | N=60 | Completed | Sponsor: Novartis Pharmaceuticals

Monotherapy • New P2 trial • Infectious Disease • Malaria

Prevalence and impact of parasite mutations in pediatric patients in Africa with uncomplicated Plasmodium falciparum malaria in a Phase II clinical evaluation of ganaplacide-lumefantrine (ASTMH 2025) - "Here we report the results from a recently completed phase II trial investigating the efficacy, safety, and tolerability of ganaplacide (KAF156), in combination with Lumefantrine-solid dispersible formulation (SDF) compared to artemether-lumefantrine (Coartem).The study was conducted from 2021 to 2024 in 295 patients aged 6 months to < 18 years diagnosed with uncomplicated Plasmodium falciparum malaria at 10 sites across 5 African countries: Burkina Faso, Côte d'Ivoire, DR Congo, Gabon and Mali. Selection of resistance markers post treatment in recurrent infections will be assessed. Both drug combinations demonstrated high efficacy in this study as previously presented."

Clinical • P2 data • Infectious Disease • Malaria • Pediatrics • ABCB1 • FUBP1

KALUMA - A pivotal Phase III trial to evaluate the efficacy, safety and tolerability of the novel anti-malarial drug ganaplacide-lumefantrine (KLU156) in uncomplicated malaria (ASTMH 2025) - P3 | "Patients were randomized 1:1 to treatment with the fixed-dose combination of ganaplacide-lumefantrine solid dispersion formulation (KLU156), or the artemether-lumefantrine control arm. A summary of results of the core phase of KALUMA will be presented at the ASTMH 2025 Annual Meeting. The study is part of the EDCTP WANECAM-II program supported by the European Union (RIA2017T-2018) and financially supported by MMV and Novartis."

Clinical • P3 data • Infectious Disease • Malaria

An investigation of single dose treatment of uncomplicated malaria using a non-artemisinin triple combination of KLU156 (ganaplacide and lumefantrine) and KAE609 (cipargamin) versus 3 day standard of care with artemether-lumefantrine (ASTMH 2025) - "Final results will be presented at the forthcoming conference. The outcomes from this part of the study should support further investigations in younger patients, down to the age of 2 years."

Hematological Disorders • Infectious Disease • Malaria

Results of the KALUMA study: Phase 3 study results of ganaplacide-lumefantrine SDF combination (ASTMH 2025) - No abstract available

P3 data • Infectious Disease • Malaria

KALUMA: Efficacy, Safety and Tolerability of KLU156 in Adults and Children ≥ 5 kg Body Weight With Uncomplicated P. Falciparum Malaria (clinicaltrials.gov) - P3 | N=1720 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Malaria

The non-artemisinin antimalarial drugs under development: a review. (PubMed, Clin Microbiol Infect) - "Although attrition remains a possibility, several promising candidate drugs with novel modes of action are advancing through clinical development. Many are expected to become available for treating uncomplicated and severe malaria within the next decade. These new antimalarials could significantly enhance malaria treatment, reduce resistance, and support global health effort toward malaria control, elimination, and, potentially, eradication."

Journal • Review • Infectious Disease • Malaria

KALUMI - A Phase II trial to evaluate the efficacy, safety and tolerability of the novel anti-malarial drug ganaplacide/lumefantrine in pediatric patients (ASTMH 2024) - P2 | "The dose tested in this part of the study was 400mg KAF156/480mg LUM-SDF given once daily with a light meal for three days for patients > 35kg body weight and adapted for children with four body-weight bands as for Coartem ® (artemether-lumefantrine). A summary of results for KALUMI will be presented at the ASTMH 2024 Annual Meeting. The study is part of the EDCTP WANECAM-II program supported by the European Union (RIA2017T-2018) and financially supported by MMV and Novartis"

Clinical • Late-breaking abstract • P2 data • Infectious Disease • Malaria • Pediatrics

KALUMI - An adaptive run-in cohort of a Phase II trial to evaluate food-effects of ganaplacide/lumefantrine in adolescent patients (ASTMH 2024) - P2 | "A summary of results including PK will be presented at the 2024 ASTMH Annual Meeting. The study is part of the EDCTP WANECAM-II program supported by the European Union (RIA2017T-2018) and financially supported by MMV and Novartis"

Clinical • Late-breaking abstract • P2 data • Infectious Disease • Malaria • Pediatrics

Results of the KALUMI study: effect of food on exposure of ganaplacide-lumefantrine SDF combination. Early indicators of transmission blocking and effect in K13 mutated parasites (ASTMH 2024) - No abstract available

Infectious Disease • Malaria

Efficacy, safety and tolerability of KAF156 in combination with LUM-SDF in pediatric population with uncomplicated Plasmodium falciparum malaria Efficacité, sécurité et tolérabilité du KAF156 en association avec la LUM-SDF dans une population pédiatrique atteinte de paludisme non compliqué à Plasmodium falciparum (clinicaltrialsregister.eu) - P2 | N=220 | Sponsor: Novartis Pharma AG

Combination therapy • New P2 trial • Infectious Disease • Malaria • Pediatrics

Pharmacokinetics of Ganaplacide and Lumefantrine in Adults, Adolescents, and Children with Plasmodium falciparum Malaria Treated with Ganaplacide Plus Lumefantrine Solid Dispersion Formulation: Analysis of Data from a Multinational Phase 2 Study. (PubMed, J Clin Pharmacol) - P2 | "Lumefantrine exposure was higher with ganaplacide-LUM-SDF than with artemether-lumefantrine, although high variability was observed. Ganaplacide and lumefantrine exposures (Cmax and AUC0-24 h) were comparable across age and body weight groups. Drug exposures needed for efficacy were achieved using the dose regimen 400 mg ganaplacide plus lumefantrine 960 mg once daily for 3 days under fasted conditions."

Journal • P2 data • PK/PD data • Infectious Disease • Malaria

In vitro evaluation of ganaplacide/lumefantrine combination against Plasmodium falciparum in a context of artemisinin resistance. (PubMed, J Antimicrob Chemother) - "All these in vitro results evidence that multi-drug resistant parasites currently in circulation in the field might not affect KAF156 efficacy, and are encouraging signs for KAF156 use in a triple ACT to preserve the use of artemisinins for as long as possible."

Journal • Preclinical • Infectious Disease • Malaria • ABCB1

PLATINUM: Platform Study to Evaluate the Efficacy and Safety of Anti-malarial Agents in Patients With Uncomplicated Plasmodium Falciparum Malaria (clinicaltrials.gov) - P2 | N=327 | Recruiting | Sponsor: Novartis Pharmaceuticals | N=207 ➔ 327 | Trial completion date: Oct 2025 ➔ May 2026

Enrollment change • Trial completion date • Infectious Disease • Malaria

KALUMA: Efficacy, Safety and Tolerability of KLU156 in Adults and Children ≥ 5 kg Body Weight With Uncomplicated P. Falciparum Malaria (clinicaltrials.gov) - P3 | N=1500 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Malaria

PLATINUM: Platform Study to Evaluate the Efficacy and Safety of Anti-malarial Agents in Patients With Uncomplicated Plasmodium Falciparum Malaria (clinicaltrials.gov) - P2 | N=207 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Monotherapy • Infectious Disease • Malaria

KALUMA: Efficacy, Safety and Tolerability of KLU156 in Adults and Children ≥ 5 kg Body Weight With Uncomplicated P. Falciparum Malaria (clinicaltrials.gov) - P3 | N=1500 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Nov 2026 ➔ Aug 2027 | Trial primary completion date: Nov 2024 ➔ Jul 2025

Trial completion date • Trial primary completion date • Infectious Disease • Malaria

KALUMA: Efficacy, Safety and Tolerability of KLU156 in Adults and Children ≥ 5 kg Body Weight With Uncomplicated P. Falciparum Malaria (clinicaltrials.gov) - P3 | N=1500 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals | Initiation date: Sep 2023 ➔ Dec 2023

Trial initiation date • Infectious Disease • Malaria

"MMV's co-developed Pyramax and ganaplacide/lumefantrine recognized by WHO's antimalarial drug resistance strategy for Africa as important in tackling the spread of resistance." (@Bwv9Lr0KUguTeMT)

Licensing / partnership • Infectious Disease

KALUMA: Efficacy, Safety and Tolerability of KLU156 in Adults and Children ≥ 5 kg Body Weight With Uncomplicated P. Falciparum Malaria (clinicaltrials.gov) - P3 | N=1500 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P3 trial • Infectious Disease • Malaria

PLATINUM: Platform Study to Evaluate the Efficacy and Safety of Anti-malarial Agents in Patients With Uncomplicated Plasmodium Falciparum Malaria (clinicaltrials.gov) - P2 | N=180 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

Combination therapy • Monotherapy • New P2 trial • Infectious Disease • Malaria