Ivermectin long acting injectable - Medincell
Alternative Names: mdc-STM; mdc-TTGLatest Information Update: 13 Nov 2023
At a glance
- Originator MedinCell S.A.
- Developer MedinCell S.A.; Monash University
- Class Antimalarials; Antineoplastics; Antiparasitics; Antivirals; Macrolides; Skin disorder therapies; Small molecules
- Mechanism of Action Chloride channel agonists
-
Orphan Drug Status
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity No
Highest Development Phases
- Phase II COVID 2019 infections
- Preclinical Malaria
Most Recent Events
- 06 Nov 2023 MedinCell plans a phase I clinical trial for Malaria in 2024
- 28 Oct 2023 No recent reports of development identified for phase-I development in COVID-2019-infections(In volunteers) in United Kingdom (PO)
- 05 Jan 2023 Adverse events and efficacy data from the phase-III SAIVE trial in COVID-19 infections released by MedinCell
Development Overview
Introduction
A long-acting single three month injectable ivermectin, is being developed by MedinCell S.A., for the treatment and prevention of malaria and COVID-2019 infections. The company develops long-acting injectable products in various therapeutic areas by combining its proprietary BEPO® technology with active ingredients already known and marketed. The BEPO® technology controls and guarantee the regular delivery of a drug at the optimal therapeutic dose for several days, weeks or months starting from the subcutaneous or local injection of a simple deposit of a few millimeters, fully bioresorbable. A single injection of three-month active ivermectin will allow for mass adoption unlike shorter-acting treatments, mostly oral, which require numerous renewal campaigns. Clinical development for COVID-2019 infections is underway in Bulgaria and United Kingdom. Preclinical development for COVID-2019 infections is underway in Australia and for malaria is underway in France.
As at October 2023, no recent reports of development had been identified for phase-I development in COVID-2019-infections (In volunteers) in United Kingdom (PO).
Company Agreements
In March 2020, MedinCell entered into a grant agreement of up to $US6.4 million over three years with Unitaid, for formulation and preclinical activities of a three-month acting injectable ivermectin in low and middle income countries (LMICs). MedinCell will grant a non-exclusive license to the Medicines Patent Pool to ensure distribution of the final product via public sector in LMICs. Under the terms of the agreement, the Unitaid-funded Medicines Patent Pool is in charge of licensing agreements for the exploitation of patents for medicines in low and middle income countries will receive a non-exclusive license for the long acting product and will work to find appropriate commercialization partners to ensure that the ivermectin product based on MedinCell technology will be accessible where it is needed. [1]
Key Development Milestones
COVID-2019 infections
In October 2022, MedinCell completed the phase II SAIVE trial that evaluated the prophylactic efficacy of ivermectin in regular, daily, oral form to simulate the continuous release of the active ingredient by a long-acting injectable for the prevention of COVID-2019 infections (mdc-TTG-CT-002; EudraCT2021-001938-19; NCT05305560). The randomised, double-blind, placebo-controlled trial was initiated in March 2022, that enrolled 399 patients in Bulgaria. The SAIVE study follows a phase I study [see trial below] that successfully confirmed the safety of daily, oral ivermectin administration over a long period of time. In January 2023, MedinCell reported that the SAIVE trial has met its primary efficacy endpoint. The company also released efficacy and adverse events data from the trial [2] [3] [4] .
Before September 2021, MedinCell submitted clinical trial applications in multiple European countries, including France, to initiate a randomised, double-blind, placebo-controlled phase II trial to confirm the efficacy of long-acting injectable formulation of ivermectin as a prophylactic treatment of COVID-2019 infections, as a regular, daily, oral form to simulate the continuous release of the active ingredient by a long-acting injectable. The outcome of the study will guide and optimise future developments of the long-acting injectable formulation of ivermectin [5] .
In September 2020, MedinCell initiated a phase I trial to evaluate pharmacokinetics, safety, tolerability of a continuous daily dosing regimen of ivermectin in healthy volunteers, to simulate the continuous release of the active ingredient by a long acting injectable (mdc-TTG-CT-001; NCT04632706). The randomised, double blind, placebo controlled, exploratory trial will enrol approximately 24 participants in the UK. In December 2020, the company reported positive safety results from the trial [6] [7] . In April 2021, the company released updated positive safety data from the trial [8] .
In March 2021, MedinCell announced that there are no safety concern that would prevent health authorities from assessing the use of ivermectin against COVID-2019 infections as a new indication [9] .
In June 2021, MedinCell and the project consortium members, IRD, IRSS and CIRDES, successfully designed, tested, and confirmed with Unitaid the selection of the lead formulation. In the same month results from preclinical studies were released by MedinCell [10] .
Results from preclinical studies established by Monash University were released by MedinCell [11] .
Malaria
In June 2023, MedinCell plans a phase I clinical trial for Malaria in 2024 [12] [13]
Drug Properties & Chemical Synopsis
- Route of administration PO, SC
- Formulation Injection, unspecified
- Class Antimalarials, Antineoplastics, Antiparasitics, Antivirals, Macrolides, Skin disorder therapies, Small molecules
- Target Chloride channel
- Mechanism of Action Chloride channel agonists
-
WHO ATC code
J05A-X (Other antivirals)
P01B (Antimalarials)
-
EPhMRA code
J5B9 (Antivirals, others)
P1D (Anti-Malarials)
Biomarkers Sourced From Trials
Indication | Biomarker Function | Biomarker Name | Number of Trials |
---|---|---|---|
bacterial infections |
Official Title |
Azelaic acid |
|
cOVID 2019 infections |
Outcome Measure |
Vascular endothelial growth factor A (VEGF) ubiquitin associated and SH3 domain containing B Tumor necrosis factor alpha (TNF-alpha) transportin 1 T-cell surface antigen CD4 T-Cell differentiation antigen CD8 ribosomal protein SA Rab9 effector protein with kelch motifs p63 Monocyte chemoattractant protein-1 (MCP-1/CCL2) mitochondrial intermediate peptidase MAPK1 major intrinsic protein of lens fiber MAFIP LANCL1 Interleukin-8 (IL-8) Interleukin-7 (IL-7) Interleukin-6 (IL-6) Interleukin-5 (IL-5) Interleukin-4 (IL-4) Interleukin-2 (IL-2) Interleukin-17 (IL-17) Interleukin-15 (IL-15) Interleukin-13 (IL-13) Interleukin-12B (IL-12p40) Interleukin-12A (IL-12p35) Interleukin-10 (IL-10) Interleukin-1 receptor antagonist (IL-1RA) interleukin 1 receptor type 1 Interleukin 1 Beta (IL-1β) Interferon Gamma (IFNg) IFN-alpha 2 Hepatocyte growth factor H3P28 Granulocyte-macrophage colony-stimulating factor (GM-CSF) G-CSF Fibroblast Growth Factor (FGF2) Epidermal growth factor (EGF) CXCL9 Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10) C-C motif chemokine 4 (CCL4 annexin A6 |
|
COVID-19 respiratory infection |
Arm Group Description |
Lactoferrin D-dimer Ascorbic acid |
|
COVID-19 respiratory infection |
Eligibility Criteria |
Ferritin C-reactive protein (CRP) |
|
filarial elephantiasis |
Eligibility Criteria |
Creatinine |
|
filarial elephantiasis |
Outcome Measure |
tubulin folding cofactor A |
|
malaria |
Arm Group Description |
Hexakis(2-methyl-2-phenylpropyl)distannoxane |
|
malaria |
Outcome Measure |
peptidylprolyl isomerase G MDR1 |
|
rosacea |
Official Title |
Azelaic acid |
|
rosacea |
Outcome Measure |
pregnancy specific beta-1-glycoprotein 2 CEA carcinoembryonic antigen related cell adhesion molecule 3 |
Biomarker
Drug Name | Biomarker Name | Biomarker Function |
---|---|---|
Ivermectin long acting injectable - Medincell | 24,25-Dihydroxyvitamin D | Arm Group Description |
ACE2 | Arm Group Label, Outcome Measure | |
AKT interacting protein | Outcome Measure | |
Alkaline phosphatase (ALPL) | Outcome Measure | |
Alpha-synuclein (aSyn) | Arm Group Description | |
ALT | Outcome Measure | |
annexin A6 | Outcome Measure | |
Ascorbic acid | Arm Group Description, Arm Group Label | |
Bilirubin | Detailed Description, Eligibility Criteria | |
C-C motif chemokine 4 (CCL4 | Outcome Measure | |
C-reactive protein (CRP) | Detailed Description, Eligibility Criteria, Outcome Measure | |
CA 15-3 | Detailed Description, Outcome Measure | |
Carbohydrate antigen 19-9 (CA 19-9) | Detailed Description, Outcome Measure | |
Cardiac Troponin I | Outcome Measure | |
CASR | Outcome Measure | |
CEA | Detailed Description, Outcome Measure | |
Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10) | Outcome Measure | |
Cholecalciferol | Arm Group Description, Brief Title, Official Title | |
complement factor properdin | Outcome Measure | |
Creatine | Outcome Measure | |
Creatinine | Detailed Description, Eligibility Criteria | |
CXCL9 | Outcome Measure | |
CYP3A4 | Arm Group Description, Detailed Description, Outcome Measure | |
Cysteamine | Arm Group Description, Arm Group Label | |
Cytidine monophosphate | Detailed Description | |
D-dimer | Arm Group Description, Brief Summary, Detailed Description, Outcome Measure | |
Epidermal growth factor (EGF) | Outcome Measure | |
esterase activator | Outcome Measure | |
Ferritin | Detailed Description, Eligibility Criteria, Outcome Measure | |
Fibrinogen | Detailed Description, Outcome Measure | |
Fibroblast Growth Factor (FGF2) | Outcome Measure | |
Fluticasone | Arm Group Description, Arm Group Label | |
fuzzy planar cell polarity protein | Brief Title | |
G-CSF | Outcome Measure | |
G6PD | Eligibility Criteria | |
Granulocyte-macrophage colony-stimulating factor (GM-CSF) | Outcome Measure | |
H3P28 | Outcome Measure | |
Hepatocyte growth factor | Outcome Measure | |
Hexakis(2-methyl-2-phenylpropyl)distannoxane | Arm Group Description | |
IFN-alpha 2 | Outcome Measure | |
Interferon Gamma (IFNg) | Outcome Measure | |
Interleukin 1 Beta (IL-1β) | Outcome Measure | |
interleukin 1 receptor type 1 | Outcome Measure | |
interleukin 6 receptor | Outcome Measure | |
Interleukin-1 receptor antagonist (IL-1RA) | Outcome Measure | |
Interleukin-10 (IL-10) | Outcome Measure | |
Interleukin-12A (IL-12p35) | Outcome Measure | |
Interleukin-12B (IL-12p40) | Outcome Measure | |
Interleukin-13 (IL-13) | Outcome Measure | |
Interleukin-15 (IL-15) | Outcome Measure | |
Interleukin-17 (IL-17) | Outcome Measure | |
Interleukin-2 (IL-2) | Outcome Measure | |
Interleukin-4 (IL-4) | Outcome Measure | |
Interleukin-5 (IL-5) | Outcome Measure | |
Interleukin-6 (IL-6) | Detailed Description, Outcome Measure | |
Interleukin-7 (IL-7) | Outcome Measure | |
Interleukin-8 (IL-8) | Outcome Measure | |
L-Aspartic acid | Outcome Measure | |
L-FABP | Outcome Measure | |
Lactoferrin | Arm Group Description, Detailed Description | |
LANCL1 | Outcome Measure | |
MAFIP | Outcome Measure | |
major intrinsic protein of lens fiber | Outcome Measure | |
MAPK1 | Outcome Measure | |
matrilin 1, cartilage matrix protein | Detailed Description | |
MDR1 | Arm Group Description, Brief Title, Eligibility Criteria, Official Title, Outcome Measure | |
mitochondrial intermediate peptidase | Outcome Measure | |
Monocyte chemoattractant protein-1 (MCP-1/CCL2) | Outcome Measure | |
p63 | Outcome Measure | |
peptidylprolyl isomerase G | Outcome Measure | |
PITRM1 | Arm Group Description | |
Prothrombin (PT) | Detailed Description | |
PTPN11 | Detailed Description, Outcome Measure | |
purinergic receptor P2Y12 | Arm Group Description | |
Rab9 effector protein with kelch motifs | Outcome Measure | |
RAS | Outcome Measure | |
Renin | Arm Group Description | |
ribosomal protein SA | Outcome Measure | |
seryl-tRNA synthetase | Official Title | |
T-Cell differentiation antigen CD8 | Outcome Measure | |
T-cell surface antigen CD4 | Brief Summary, Eligibility Criteria, Outcome Measure | |
Thyroid stimulating hormone beta (TSH) | Eligibility Criteria | |
Tissue factor | Detailed Description | |
TLX1 neighbor | Outcome Measure | |
TNFRSF1A | Outcome Measure | |
transportin 1 | Outcome Measure | |
Tubulin beta class IVb | Outcome Measure | |
tubulin folding cofactor A | Eligibility Criteria, Outcome Measure | |
Tumor necrosis factor alpha (TNF-alpha) | Detailed Description, Outcome Measure | |
ubiquitin associated and SH3 domain containing B | Outcome Measure | |
Uric acid | Eligibility Criteria | |
Vascular endothelial growth factor A (VEGF) | Outcome Measure | |
Vitamin D3 | Arm Group Description, Brief Title, Official Title |
Development Status
Summary Table
Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
---|---|---|---|---|---|---|---|
COVID 2019 infections | - | Prevention | Phase II | Bulgaria | PO / unspecified | MedinCell S.A. | 28 Mar 2022 |
COVID 2019 infections | - | - | Preclinical | Australia | SC / Injection | MedinCell S.A., Monash University | 06 Apr 2020 |
COVID 2019 infections | Male | In volunteers | No development reported (I) | United Kingdom | PO / unspecified | MedinCell S.A. | 28 Oct 2023 |
Malaria | - | - | Preclinical | France | unspecified / Injection | MedinCell S.A. | 25 Mar 2020 |
Commercial Information
Involved Organisations
Organisation | Involvement | Countries |
---|---|---|
MedinCell S.A. | Originator | France |
MedinCell S.A. | Owner | France |
Medicines Patent Pool | Market Licensee | Switzerland |
UNITAID | Funder | Switzerland |
Monash University | Collaborator | Australia |
Scientific Summary
Adverse Events
In a phase II trial, there were no safety signals related to daily intake of ivermectin, 200 µg/kg on Day 1 then 100 µg/kg daily from Day 2 to Day 28 [2] [4] .
In a phase I trial of ivermectin, there were no side effects observed with all the three doses upto 100 µg/kg including 50mcg/kg and 75mcg/kg [8] [6] [7] .
Pharmacodynamics
Summary
Results from in-vivo proof of concept showed that injectable long-acting formulation of ivermectin demonstrated potent efficacy with a 3-month mosquitocidal effectiveness when administered to cattle [10] .
In preclinical studies, ivermectin killed coronavirus in a laboratory setting in 48 hours. Additionally, a single treatment of ivermectin also demonstrated a ~5000-fold reduction in virus at 48h in cell culture [11]
Future Events
Expected Date | Event Type | Description | Updated |
---|---|---|---|
31 Dec 2023 | Trial Update | MedinCell plans a phase I clinical trial for Malaria in 2024 [13] | 13 Nov 2023 |
31 Mar 2021 | Regulatory Status | MedinCell announces intention to submit marketing authorization application for ivermectin long-acting injectable by early 2021 [14] | 01 Oct 2020 |
31 Dec 2020 | Trial Update | MedinCell plans to enter the preliminary preclinical stages of regulatory development by the end of 2020 [14] | 01 Oct 2020 |
Development History
Event Date | Update Type | Comment |
---|---|---|
06 Nov 2023 | Trial Update | MedinCell plans a phase I clinical trial for Malaria in 2024 [13] Updated 13 Nov 2023 |
28 Oct 2023 | Phase Change - No development reported | No recent reports of development identified for phase-I development in COVID-2019-infections(In volunteers) in United Kingdom (PO) Updated 28 Oct 2023 |
05 Jan 2023 | Scientific Update | Adverse events and efficacy data from the phase-III SAIVE trial in COVID-19 infections released by MedinCell [2] Updated 09 Jan 2023 |
13 Oct 2022 | Trial Update | MedinCell completes the phase-II SAIVE trial in COVID-2019 infections in Bulgaria (PO) (NCT05305560) Updated 09 Jan 2023 |
28 Mar 2022 | Phase Change - II | Phase-II clinical trials in COVID-2019 infections (Prevention) in Bulgaria (PO) [3] (NCT05305560) Updated 31 Mar 2022 |
21 Dec 2021 | Biomarker Update | Biomarkers information updated Updated 23 Dec 2021 |
01 Sep 2021 | Regulatory Status | MedinCell files Clinical Trial Applications in France and other European countries for COVID-2019 infections (Preventions) before September 2021 [5] Updated 02 Sep 2021 |
01 Sep 2021 | Trial Update | Medincell plans a phase II trial for COVID-2019 infections (Prevention) in France and Europe (SC,Controlled release) [5] Updated 02 Sep 2021 |
14 Jun 2021 | Scientific Update | Pharmacodynamics data from preclinical studies in Malaria released by MedinCell [10] Updated 21 Jun 2021 |
21 Apr 2021 | Scientific Update | Positive updated safety data from a phase I trial in COVID-2019 infections released by MedinCell [8] Updated 26 Apr 2021 |
22 Dec 2020 | Scientific Update | Adverse events data from a phase I trial in COVID-2019 infections released by MedinCell [6] Updated 22 Dec 2020 |
29 Sep 2020 | Regulatory Status | MedinCell announces intention to submit marketing authorization application for ivermectin long-acting injectable by early 2021 [14] Updated 01 Oct 2020 |
29 Sep 2020 | Trial Update | MedinCell plans to enter the preliminary preclinical stages of regulatory development by the end of 2020 [14] Updated 01 Oct 2020 |
22 Sep 2020 | Phase Change - I | Phase-I clinical trials in COVID-2019 infections (In volunteers) in United Kingdom (PO) (NCT04632706) Updated 25 Nov 2020 |
06 Apr 2020 | Phase Change - Preclinical | Preclinical trials in COVID-2019 infections in Australia (SC) [11] Updated 09 Apr 2020 |
06 Apr 2020 | Scientific Update | Pharmacodynamics data from preclinical studies in COVID-2019 infections released by MedinCell [11] Updated 09 Apr 2020 |
25 Mar 2020 | Licensing Status | MedinCell signs a grant agreement with Unitaid for injectable ivermectin for Malaria [1] Updated 01 Apr 2020 |
25 Mar 2020 | Phase Change - Preclinical | Preclinical trials in Malaria in France (unspecified route) [1] Updated 31 Mar 2020 |
References
-
MedinCell Receives $ 6.4 Million Grant From Unitaid to Fight Malaria.
Media Release -
MedinCell announces positive results for the SAIVE clinical study in prevention of Covid-19 infection in a contact-based population.
Media Release -
MedinCell: Inclusion of First Participants in New Covid-19 Prophylaxis Clinical Trial SAIVE.
Media Release -
A Multicentre Randomised, Double-Blind, Placebo-controlled, Study to Evaluate the efficAcy and Safety of Oral IVErmectin Tablets in the Prevention of COVID-19
ctiprofile -
MedinCell Provides an Update on Its Product Portfolio, Following the FDA Acceptance of New Drug Application for the Product mdc-IRM.
Media Release -
Covid-19: MedinCell Presents Positive First Results From the Clinical Trial Aiming at Validating the Safety of Continuous Administration of Ivermectin.
Media Release -
A Randomised, Double-Blind, Placebo-Controlled, Exploratory Phase I Trial Assessing the Pharmacokinetic Profile, Safety and Tolerability of a Continuous Daily Dosing Regimen of Active IMP in Healthy Volunteers
ctiprofile -
Clinical Trial Conducted by MedinCell Confirms the Safety of Continuous Administration of Ivermectin.
Media Release -
Covid-19: MedinCell Publishes an Extensive Ivermectin Safety Expert Analysis.
Media Release -
MedinCells Long-Acting Injectable to Fight Malaria Ready to Enter Regulatory Development.
Media Release -
MedinCell Has Launched a COVID-19 Research Initiative Based on Its Experience to Formulate Long-Acting Injectable Ivermectin.
Media Release -
MedinCell announces its full year financial results.
Media Release -
MedinCell at the 2023 Jefferies Global Healthcare Conference -London, 14-16 November.
Media Release -
MedinCell Initiates the First Clinical Trial of Its Covid-19 Prevention Program.
Media Release
Adis International Ltd. Part of Springer Science+Business Media
© Springer Nature Switzerland AG