Delving into the Latest Updates on Ferroquine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Hemozoin

Action

inhibitors

Mechanism

Hemozoin inhibitors

Therapeutic Areas

Infectious Diseases

Active Indication-

Inactive Indication

Malaria, Falciparum

Originator Organization

Sanofi

Active Organization-

Inactive Organization

Sanofi

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC23H24ClFeN3

InChIKeyDDENDDKMBDTHAX-UHFFFAOYSA-N

CAS Registry185055-67-8

Malaria is caused by protozoan parasites of the genus Plasmodium and it is the most important parasitic disease in terms of mortality and morbidity. Estimates of 247 million malaria cases and 619.000 deaths worldwide were reported by WHO for the year 2021 (1). Plasmodium falciparum can lead to severe malaria and accounts for 90% of malaria deaths that mainly occur in children below the age of 5 years in Sub-Saharan Africa.
A simplified treatment regimen, ideally a single-day cure (or at most 2-day dosing regimen), of uncomplicated malaria due to P. falciparum would be the magic in the antimalarial armamentarium. Improving treatment adherence is one of the key factors in reducing mortality and morbidity and also the transmission of malaria, and such a regimen would substantially increase adherence. To find a new non-artemisinin combination therapy with a shorter regimen, ideally, a single-dose cure, with low resistance potential would be the aim. The two compounds tested here are ZY19489, a triaminopyrimidine, and ferroquine (FQ), a next-generation 4-aminoquinoline. Both compounds show unique features in terms of long half-life, and activity against current drug-resistant strains.
Therefore, the main goal of this clinical trial is to assess the safety of the ZY19489-FQ combination given as a 1- or 2-day dose regimen.

Start Date30 Aug 2024

Sponsor / Collaborator

Zydus Lifesciences Ltd.

NCT03660839

/ CompletedPhase 2

A Randomized, Open Label, Parallel-group, Single Dose Regimen, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 Dose Levels of Artefenomel (OZ439) Given in Combination With Ferroquine (FQ) and FQ Alone, in African Patients With Uncomplicated Plasmodium Falciparum Malaria

Primary Objective:
To show the contribution of artefenomel (OZ439) to the clinical and parasiticidal effect of OZ439/Ferroquine (FQ) combination by analyzing exposure-response of OZ439 measured by Day 28 polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) for the effect and the area under the curve (AUC) of OZ439 as pharmacokinetic (PK) predictor.
Secondary Objectives:
To evaluate the exposure-response of OZ439 combined with FQ on crude Day 28 ACPR.
To evaluate the dose response of OZ439 combined with FQ on PCR-corrected and crude Day 28 ACPR.
To evaluate the dose-response of OZ439 combined with FQ on selected secondary endpoints.
To evaluate the safety and tolerability of different dosages of OZ439 in combination with FQ and FQ alone.
To characterize the PK of OZ439 in plasma, and of FQ and its active metabolite SSR97213 in blood.

Start Date11 Sep 2018

Sponsor / Collaborator

Sanofi

[+1]

NCT02497612

/ TerminatedPhase 2

A Randomized, Double-blind, Phase IIb Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine (FQ) With Artefenomel (OZ439) in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria

Primary Objective:
To determine whether a single dose combination of OZ439 (Artefenomel)/FQ (Ferroquine) was an efficacious treatment for uncomplicated Plasmodium falciparum malaria in adults and children.
Secondary Objectives:
To evaluate the efficacy of OZ439/FQ:
To determine the incidence of recrudescence and re-infection.
To determine the time to relief of fever and parasite clearance.
To evaluate the safety and tolerability of OZ439/FQ in adults and children.
To characterize the pharmacokinetics of OZ439 in plasma, FQ and its active metabolite SSR97213 in blood.
To determine the blood/plasma ratio for FQ and SSR97213 in some participants at limited time points in selected sites.

Start Date25 Jul 2015

Sponsor / Collaborator

Sanofi

[+1]

100 Clinical Results associated with Ferroquine

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100 Translational Medicine associated with Ferroquine

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100 Patents (Medical) associated with Ferroquine

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156

Literatures (Medical) associated with Ferroquine

01 Mar 2025·Applied Organometallic Chemistry

Advances in the Potential of Quinoline‐Derived Metal Complexes as Antimalarial Agents: A Review

Author: Gonçalves, Raoni Schroeder Borges ; Peron, Carla ; Moura, Sidnei

ABSTRACTQuinolines obtained from native trees of South and Central America, of the genus Cinchona, have been used since the 17th century for the treatment of malaria. However, it was only in 1820 that quinine had its structure elucidated, and subsequently, during the 20th century, several synthetic derivatives were produced with quinine superior activities. In parallel, the search for the synthesis of metal complex compounds for the treatment of malaria dates from 1994, with the development of ferroquine, an iron complex derived from chloroquine, developed by Biot and collaborators at Lille University. After, there are several metal complexes synthesized from quinine with various metals, such as ruthenium, gold, iridium, and platinum, over the last 30 years, which are the aims of this review. This review identified 84 quinoline–metal complexes reported across 25 studies, with the gold complex (Complex 63) showing significant potency against the FcBI strain (IC50 10 nM), outperforming chloroquine (CQ, 50 nM), indicating that metal coordination enhances the drug's action. The ruthenium complex (Complex 03) exhibited activity against PFB but was less effective than CQ (IC50 22.5 vs. 8.2 nM). Other complexes, such as Au(III) (Complex 61), Ir(I) (Complex 52), and Ir(II) (Complex 50), also demonstrated promising results with varying effectiveness across different strains. Structural features, including linear geometry in Au(I) complexes and square planar or piano stool geometries in Ru(II) and Ir complexes, play crucial roles in influencing their biological activity. These findings highlight the potential of metal coordination in improving antimalarial efficacy.

01 Mar 2025·Clinical Microbiology and Infection

The non-artemisinin antimalarial drugs under development: a review

Review

Author: Mombo-Ngoma, Ghyslain ; Ramharter, Michael ; Okwu, Dearie Glory ; Duparc, Stephan ; Zoleko Manego, Rella ; Kremsner, Peter Gottfried

BACKGROUNDIn 2022, malaria caused approximately 249 million cases and 608,000 deaths, primarily in Africa. Current treatments target asexual blood-stage parasites, gametocytes, and liver hypnozoites. Standard guidelines recommend a 3-day course of artemisinin-based combination therapies as a first-line treatment of uncomplicated malaria and parenteral artesunate for severe malaria. However, the emergence of partial resistance to artemisinin derivatives threatens the treatment efficacy, highlighting the urgent need for novel antimalarial drugs.OBJECTIVESThis review summarizes recent progress in the clinical development of antimalarials particularly non-artemisinin compounds under target product profile-1.SOURCESData were gathered from Medicines for Malaria Venture (MMV)'s portfolio and clinical trial databases between 2020 and 2024.CONTENTSixteen clinical trials were reviewed, including safety and efficacy studies involving healthy volunteers, experimentally infected volunteers, asymptomatic Plasmodium falciparum carriers and malaria patients. Six trials evaluated the safety and tolerability of MMV533, ZY19489, INE963, GSK701/MMV367 and intravenous KAE609 in healthy volunteers. Efficacy trials involving experimentally infected volunteers assessed ZY19489 and GSK701/MMV367, whereas studies on asymptomatic carriers tested ZY19489/ferroquine and cabamiquine/pyronaridine. Trials on malaria patients investigated combinations of ganaplacide/lumefantrine-SDF, cabamiquine/pyronaridine, both oral and intravenous cipargamin and INE963.IMPLICATIONSAlthough 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 efforts towards malaria control, elimination and, potentially, eradication.

28 Oct 2024·JACS Au

Pyrimidine Azepine Targets the Plasmodium bc₁ Complex and Displays Multistage Antimalarial Activity

Article

Author: Silva-Mendonça, Sabrina ; Usui, Miho ; Aguiar, Anna Caroline C. ; Moura, Igor M. R. ; Long, Carole A. ; Benavente, Ernest D. ; da Silva Araujo, Maisa ; Calit, Juliana ; Eastman, Richard T. ; Bargieri, Daniel Y. ; Williamson, Kim C. ; Miura, Kazutoyo ; Araújo, Jessica E. ; Simeonov, Anton ; Andrade, Carolina H. ; Medeiros, Jansen F. ; Deng, Bingbing ; Prajapati, Surendra K. ; Annunciato, Yasmin

Malaria control and elimination efforts would benefit from the identification and validation of new malaria chemotherapeutics. Recently, a transgenic Plasmodium berghei line was used to perform a series of high-throughput in vitro screens for new antimalarials acting against the parasite sexual stages. The screens identified pyrimidine azepine chemotypes with potent activity. Here, we validate the activity of PyAz90, the most potent pyrimidine azepine chemotype identified, against P. falciparum and P. vivax in the asexual and sexual stages. PyAz90 blocked parasite transmission to the mosquito vector at nanomolar concentrations and inhibited in vitro asexual parasite multiplication with a fast-action profile. Through the generation of P. falciparum PyAz90-resistant parasites and in vitro assays of mitochondrial activity, we identified cytochrome b as a molecular target of PyAz90. This work characterizes a promising chemotype that can be explored for the future development of new antimalarials targeting the Plasmodium cytochrome bc ₁ complex.

100 Deals associated with Ferroquine

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Malaria, Falciparum	Phase 2	Kenya	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	Cameroon	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	Benin	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	Burkina Faso	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	Tanzania	Sanofi	01 Oct 2009
Malaria, Falciparum	Phase 2	Gabon	Sanofi	01 Oct 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03660839 (Pubmed)	Phase 2	Malaria, Falciparum	140	400 mg ferroquine	gqqkioupnk(oihhxyuukp) = Adverse events (AEs) of any cause occurred in 51.4% (18/35) of patients with ferroquine 400 mg alone, and 58.3% (21/36), 66.7% (24/36), and 72.7% (24/33) with 300, 600, and 1000 mg artefenomel, respectively rzjlhjxgfb (ftnevilpal ) View more	-	03 Jan 2023
				400 mg ferroquine plus artefenomel 300 mg
NCT02497612 (Pubmed \| Malar J) Manual	Phase 2	Malaria, Falciparum	373	artefenomel+ferroquine	(fgagzqalvu) = 78.4% [64.7; 88.7%] to 91.7% [81.6; 97.2%] for the 400 mg to 1200 mg mdmtmfuleh (bpwzwqzuzh ) View more	Negative	19 May 2021
NCT03660839 (CTgov)	Phase 2	Malaria, Falciparum	140	Artefenomel (OZ439)+Ferroquine (SSR97193) (Ferroquine 400 mg + Artefenomel 300 mg)	ainbkzolkg(veqjcaehup) = axsfiypylw gbdnrngvmd (puxlbaszpq, dsqoyczkmg - rhwvgqtykw) View more	-	02 Dec 2020
				Artefenomel (OZ439)+Ferroquine (SSR97193) (Ferroquine 400 mg + Artefenomel 600 mg)	ainbkzolkg(veqjcaehup) = slfxrmmqwd gbdnrngvmd (puxlbaszpq, beashqrhlg - aufmyiwiph) View more
NCT02497612 (FALCI, CTgov)	Phase 2	Malaria, Falciparum	377	Placebo+Artefenomel+Ferroquine SSR97193 (Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg))	tvijylupoe(vkupmaqwjj) = smnlqdeufw pbdnopgyib (hbtqyswfsy, wlnuubjvvw - mqkrtleyyk) View more	-	19 Oct 2020
				Placebo+Artefenomel+Ferroquine SSR97193 (Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg))	tvijylupoe(vkupmaqwjj) = ywnihywprl pbdnopgyib (hbtqyswfsy, yrivwqeyjg - pyqepfwysi) View more
NCT00563914 (Pubmed \| Trans R Soc Trop Med Hyg \| Am J Trop Med Hyg) Manual	Phase 2	Malaria, Falciparum	72	Artesunate+Ferroquine	(nigjgfwedl) = mild increases（grade 1 toxicity）in ALT levels with a dose trend starting at 400 mg；two grade 2 ALT events（200 mg 1 pt，600 mg 1 pt） ufmvmyeeuq (rdwghgaidb ) View more	Positive	01 Aug 2017
				Artesunate+Amodiaquine
NCT00988507 (Pubmed \| Lancet Infect Dis)	Phase 2	Malaria, Falciparum	326	Artesunate 4 mg/kg + Ferroquine 2 mg/kg	swobausfnq(nrscuvvtec) = jtzfnrcpyo nkwhdxtybs (goccddxlms, 90 - 100)	Positive	01 Dec 2015
				Artesunate 4 mg/kg + Ferroquine 4 mg/kg	swobausfnq(nrscuvvtec) = swkarkmpgb nkwhdxtybs (goccddxlms, 93 - 100)