Delving into the Latest Updates on Artefenomel Mesylate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target-

Mechanism-

Therapeutic Areas

Infectious Diseases

Active Indication

Malaria

Inactive Indication

Malaria, Falciparum

Originator Organization

Sanofi

Active Organization

Sanofi

Inactive Organization

Clinical Network Services Pty Ltd.Q-Pharm Pty Ltd.

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC28H39NO5

InChIKeyXLCNVWUKICLURR-VFXIDCLRSA-N

CAS Registry1029939-86-3

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]

NCT03542149 / CompletedPhase 1IIT

Phase 1b to Assess Safety, Tolerability, Pharmacokinetic Profile, and Antimalarial Activity of Single Doses of Co-administered OZ439and PQP Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Adult Volunteers

A single-centre Phase 1b study to assess the safety, tolerability, pharmacokinetic profile, and antimalarial activity of single doses of coadministered artefenomel (OZ439) and piperaquine phosphate (PQP) against early Plasmodium falciparum blood stage infection in healthy adult volunteers.

Start Date23 Apr 2018

Sponsor / Collaborator

MMV Medicines for Malaria Venture

[+3]

NCT04069221 / CompletedPhase 1IIT

An Open-label, Two-part Study to Determine the Absolute Bioavailability (BA) of OZ439 Using Simultaneous Intravenous [14C]-OZ439 Microdose/800mg Oral Dosing and to Investigate the Pharmacokinetics (PK) of OZ439 Granules Administered as Single Doses Suspended in Different Volumes and When Co-administered With a Single Dose of Cobicistat, a Strong CYP3A4 Inhibitor, to Healthy Subjects in Fasted State

This study is an open-label, two-part study to determine the absolute bioavailability (BA) of OZ439 using simultaneous intravenous [14C]-OZ439 microdose/800mg oral dosing and to investigate the pharmacokinetics (PK) of OZ439 granules administered as single doses suspended in different volumes and when co-administered with a single dose of Cobicistat, a strong CYP3A4 inhibitor, to healthy subjects in fasted state.

Start Date28 Feb 2017

Sponsor / Collaborator

MMV Medicines for Malaria Venture

100 Clinical Results associated with Artefenomel Mesylate

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100 Translational Medicine associated with Artefenomel Mesylate

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100 Patents (Medical) associated with Artefenomel Mesylate

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65

Literatures (Medical) associated with Artefenomel Mesylate

10 Oct 2024·ACS Medicinal Chemistry Letters

Synthesis and In Vivo Profiling of Desymmetrized Antimalarial Trioxolanes with Diverse Carbamate Side Chains

Article

Author: Rosenthal, Philip J. ; Legac, Jenny ; Renslo, Adam R. ; Jaishankar, Priyadarshini ; Kim, Julie ; Gonciarz, Ryan L. ; Cheng, Ke ; Klope, Matthew T. ; Tapia Cardona, Juan A. ; Chen, Jun

The recent withdrawal of artefenomel from clinical development leaves no endoperoxide-class agents in the antimalarial pipeline. Synthetic endoperoxides with a desymmetrized structure have demonstrated promising physiochemical and in vivo properties. Here we expand on our initial investigation of trans-3″ carbamate substitution with a diverse array of amine-, alcohol-, and sulfinyl-terminated analogues prepared in (S,S) and (R,R) configurations. In general, this chemotype combines low-nM antiplasmodial activity with excellent aqueous solubility but widely varying human liver microsome (HLM) stability. We evaluated 20 novel analogues in the P. berghei mouse malaria model, identifying new analogues such as RLA-4767 (9a) and RLA-5489 (9d), with HLM stability and pharmacokinetic profiles superior to analogues from our initial report (e.g., RLA-4776, 8a). These new leads approach or equal the efficacy of artefenomel after two daily oral doses of 10 mg/kg, thus revealing a promising chemotype with the potential to deliver development candidates.

01 Mar 2024·Headache: The Journal of Head and Face Pain

A randomized, open‐label, 5‐period crossover study evaluating the pharmacokinetics and safety of a single dose of intranasal dihydroergotamine (DHE) powder (STS101), intramuscular DHE mesylate, and liquid nasal spray DHE in healthy adults

Article

Author: Bermudez, Maria ; Levy, Jeff ; Lipton, Richard B. ; Hussey, Elizabeth ; Albrecht, Detlef ; Hu, Jerry

AbstractObjectiveTo compare the safety and pharmacokinetics (PK) of dihydroergotamine (DHE) after administration of intranasal DHE powder (STS101), liquid nasal spray (LNS) DHE mesylate, and intramuscular (IM) DHE mesylate injection in healthy participants.BackgroundDHE is an effective acute migraine treatment; however, self‐administration difficulties have prevented its broader role in the management of migraine.MethodsThis randomized, active‐controlled, five‐period crossover study was conducted over 5 weeks separated by 1‐week washout periods. Three STS101 dosage strengths (5.2, 7.0, 8.6 mg), and one dose each of LNS DHE 2.0 mg, and IM DHE 1.0 mg, were administered to 36 healthy participants. Liquid chromatography, tandem mass spectrometry was used to determine DHE (including its 8′OH‐DHE metabolite) plasma levels and to calculate PK parameters (Cmax, Tmax, AUC0‐2h, AUC0‐last, AUC0‐inf, and t1/2). Safety was evaluated by monitoring adverse events (AEs), vital signs, electrocardiograms, nasal examinations, and laboratory parameters.ResultsThirty‐six participants (mean age 36 years; 19% Hispanic Black and 81% Hispanic White) were enrolled. DHE plasma concentrations rose rapidly after STS101 5.2, 7.0, and 8.6 mg and IM DHE injection, with mean concentrations greater than 2000 pg/mL for all STS101 dose strengths at 20 min. All STS101 dose strengths showed approximately 3‐fold higher Cmax, AUC0‐2h, and AUC0‐inf, than the LNS DHE. The mean AUC0‐inf of STS101 7.0 and 8.6 mg were comparable to IM DHE (12,600 and 13,200 vs. 13,400 h × pg/mL). All STS101 dose strengths showed substantially lower variability (CV%) compared to LNS DHE for Cmax (35%–41% vs. 87%), and AUC0‐inf (37%–46% vs. 65%). STS101 was well tolerated, and all treatment‐emergent AEs were mild and transient.ConclusionSTS101 showed rapid absorption and was well tolerated with mild and transient treatment‐emergent AEs. Achieving effective DHE plasma concentrations within 10 min, STS101 displayed a favorable PK profile relative to the LNS with higher Cmax, AUC0‐2h, and AUC0inf, and with greater response consistency. The AUC0‐inf was comparable to IM DHE.

01 Jan 2024·EXCLI journal

Recent advances, challenges and updates on the development of therapeutics for malaria.

Review

Author: Bansal, Nitin ; Sharma, Prabodh Chander ; Chopra, Hitesh ; Deep, Aakash ; Aggarwal, Navidha ; Kumar, Davinder ; Kumar, Surender ; Marwaha, Rakesh Kumar ; Narasimhan, Balasubramanian ; Kumar, Virender ; Nandal, Rimmy

Malaria has developed as a serious worldwide health issue as a result of the introduction of resistant Plasmodium species strains. Because of the common chemo resistance to most of the existing drugs on the market, it poses a severe health problem and significant obstacles in drug research. Malaria treatment has evolved during the last two decades in response to Plasmodium falciparum drug sensitivity and a return of the disease in tropical areas. Plasmodium falciparum is now highly resistant to the majority of antimalarial drugs. The parasite resistance drew focus to developing novel antimalarials to combat parasite resistance. The requirement for many novel antimalarial drugs in the future year necessitates adopting various drug development methodologies. Different innovative strategies for discovering antimalarial drugs are now being examined here. This review is primarily concerned with the description of newly synthesized antimalarial compounds, i.e. Tafenoquine, Cipargamin, Ferroquine, Artefenomel, DSM265, MMV390048 designed to improve the activity of pure antimalarial enantiomers. In this review, we selected the representative malarial drugs in clinical trials, classified them with detailed targets according to their action, discussed the relationship within the human trials, and generated a summative discussion with prospective expectations.

100 Deals associated with Artefenomel Mesylate

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11809

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Malaria	Phase 3	-	Sanofi	-
Malaria, Falciparum	Discovery	BF	Sanofi	25 Jul 2015
Malaria, Falciparum	Discovery	KE	Sanofi	25 Jul 2015
Malaria, Falciparum	Discovery	BJ	Sanofi	25 Jul 2015
Malaria, Falciparum	Discovery	GA	Sanofi	25 Jul 2015
Malaria, Falciparum	Discovery	MZ	Sanofi	25 Jul 2015
Malaria, Falciparum	Discovery	VN	Sanofi	25 Jul 2015
Malaria, Falciparum	Discovery	UG	Sanofi	25 Jul 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03542149 (CTgov)	Phase 1	Malaria	24	200 mg OZ 439+640 mg Piperaquine phosphate (Cohort 1:Treatment Group B: 200mg of OZ439 and 640 mg PQP)	sfueitwbtp(pbdxzhotxb) = esbbdfohef qifxopnxcc (xposapxluz, cffljziain - jbtsozjuqy) View more	-	10 May 2024
				200 mg OZ 439+480 mg Piperaquine phosphate (Cohort 1: Treatment Group A: 200mg of OZ439 and 480 mg PQP)	sfueitwbtp(pbdxzhotxb) = jklbxvcutk qifxopnxcc (xposapxluz, mgzrzaamfg - siegoddkpt) View more
NCT02573857 \| NCT02389348 (Pubmed \| J Antimicrob Chemother)	Phase 1/2	Malaria, Falciparum	-	OZ439 800mg + DSM265 450mg	xjltljczsz(mevdrtmvpo) = npyszipouf jfnqazjncj (ifahbpmxut )	-	28 Jun 2021
NCT02497612 (Pubmed \| Malar J) Manual	Phase 2	Malaria, Falciparum	373	artefenomel+ferroquine	(vufbzfjotv) = 78.4% [64.7; 88.7%] to 91.7% [81.6; 97.2%] for the 400 mg to 1200 mg umdzvmpmhm (mbzypysfws ) View more	Negative	19 May 2021
NCT03660839 (CTgov)	Phase 2	Malaria, Falciparum	140	Artefenomel (OZ439)+Ferroquine (SSR97193) (Ferroquine 400 mg + Artefenomel 300 mg)	rnncyfogra(bmqufzukky) = patscncuel qossubryhb (jxibbnieee, qyjsosjtzp - mqobzwzcmd) View more	-	02 Dec 2020
				Artefenomel (OZ439)+Ferroquine (SSR97193) (Ferroquine 400 mg + Artefenomel 600 mg)	rnncyfogra(bmqufzukky) = sdkwmnuoxn qossubryhb (jxibbnieee, anobpslina - pyzlhxnxaz) View more
NCT02497612 (FALCI, CTgov)	Phase 2	Malaria, Falciparum	377	Placebo+Artefenomel+Ferroquine SSR97193 (Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg))	gerkorourc(ubxqtldohp) = zgvawgyidg bpaqzkoisd (ocpwmriwzl, hfdutrbgjg - zievlksdtn) View more	-	19 Oct 2020
				Placebo+Artefenomel+Ferroquine SSR97193 (Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg))	gerkorourc(ubxqtldohp) = icnsylspwo bpaqzkoisd (ocpwmriwzl, mvrryzszaj - mlojbcrgbt) View more
NCT02573857 (DSMOZ-2, CTgov)	Phase 1/2	Malaria	16	DSM265 (DSM265 P. Falciparum)	zjgjuceoyc(clspjscbjc) = fbqlexrwye pohxzureev (hfnyhsxngd, vxnupppqvr - sbkehyijyi) View more	-	05 Jun 2020
				OZ439 (OZ439 P. Vivax)	zjgjuceoyc(clspjscbjc) = njrtzkpmnc pohxzureev (hfnyhsxngd, spikoighyg - qluqlhqglq) View more
NCT02573857 (Pubmed \| Am J Trop Med Hyg)	Phase 1/2	Malaria, Vivax	8	Artefenomel 200 mg	loghlbsnya(wpsyiiozta) = raxyzlmigf ucldbczzsg (bzatljayer ) View more	Positive	01 Jun 2020
NCT02431650 (OZGAM, CTgov)	Phase 1/2	Malaria	11	Primaquine (Primaquine 15mg)	sdkrtnsxqm(omjgxlruer) = gofwnatpkk dixthbrnan (vbvtfnvaem, kionpmhizs - hmmielelpw) View more	-	26 May 2020
				OZ439 (OZ439 500mg)	sdkrtnsxqm(omjgxlruer) = ozsiloolhs dixthbrnan (vbvtfnvaem, yqjbwyvvlh - egawzmjrwn) View more
NCT02389348 (Pubmed) Manual	Phase 1/2	Malaria, Falciparum	13	Artefenomel+DSM265 (Cohort 1)	(adzbjpmisk) = nkmvzthpbf wkehngkmox (lcsrmxwtsq ) View more	Positive	20 Dec 2019
				Artefenomel+DSM265 (Cohort 2)	(adzbjpmisk) = cqchvvsdmp wkehngkmox (lcsrmxwtsq ) View more
NCT02083380 (Pubmed)	Phase 2	Malaria, Falciparum	448	Artefenomel 800 mg + PQP 640 mg	lnnxfrxbkb(plerjrtvdk) = qcddetrvll xuvnlarqwf (iesetdrdwj, 61.13 - 79.19)	-	09 Oct 2017
				Artefenomel 800 mg + PQP 960 mg	lnnxfrxbkb(plerjrtvdk) = njzymrworr xuvnlarqwf (iesetdrdwj, 59.13 - 76.66)