Favipiravir - Sihuan Pharmaceutical Holdings Group
Alternative Names: jk 05Latest Information Update: 28 Mar 2023
At a glance
- Originator Academy of Military Medical Sciences
- Developer Sihuan Pharmaceutical Holdings Group
- Class Small molecules
- Mechanism of Action RNA inhibitors; RNA replicase inhibitors
-
Orphan Drug Status
No
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity Yes
Highest Development Phases
- No development reported Bunyavirus infections; COVID 2019 infections; Ebola virus infections; Influenza virus infections; Viral haemorrhagic fevers; Yellow fever
Most Recent Events
Development Overview
Introduction
Sihuan Pharmaceutical Holdings Group is developing oral favipiravir (earlier known as jk 05), a small molecule, selective inhibitor of RNA polymerase, for the treatment of COVID-2019 infections. The broad spectrum antiviral was originated by Institute of Microbiology and Epidemiology of the Chinese Academy of Military Medical Sciences and licensed to Sihuan. Chinese media reports state that the government has donated the drug, to fight the 2014 Ebola outbreak in West Africa. After oral absorption, the drug is converted into a bioactive nucleoside triphosphate compound, which is similar to purine, and can compete with purine to inhibit RNA polymerase, inhibiting virus replication. The nucleoside triphosphate compound of Favipiravir can also be inserted into the virus RNA chain and acts as RNA inhibitor by inducing fatal mutation of the virus. Clinical development is underway for COVID-2019 infections in China.
Favipiravir shows anti-Ebola activity and actuivity against other RNA viruses including, influenza, yellow fever, viral haemorrhagic fevers and bunyavirus infections [1] .
Favipiravir was being developed for Ebola virus infections, however as at November 2017, no recent reports of clinical development had been identified for the development in China.
Favipiravir was being developed for Bunyavirus infections, influenza virus infections, viral haemorrhagic fevers and yellow fever, however as at November 2018, no recent reports of development had been identified for preclinical development in China for these indications.
As at March 2023, no recent reports of development had been identified for clinical-Phase-Unknown development in COVID-2019-infections in China (PO, Tablet).
Company Agreements
In October 2014, Beijing Sihuan Pharmaceutical Co Ltd, a subsidiary of the Sihuan Pharmaceutical Holdings Group Ltd, entered into a collaborative development agreement with the Institute of Microbiology and Epidemiology of the Academy of Military Medical Sciences (AMMS), to collaborate for anti-Ebola drug favipiravir (jk-05). Under the terms of the agreement, the Sihuan Pharmaceutical Holdings Group will pay a technology transfer and drug development fee amounting to RMB 10 million to AMMS for the ownership and franchise of the drug. Payment will be settled in installments based on the progress of drug development, until approval for production is received. Sihuan Pharmaceutical Holdings Group and AMMS will support further research and development efforts on favipiravir as a broad-spectrum antiviral drug, and will ensure its manufacture and launch to the market by Beijing Sihuan and addition of the drug to the national reserve. Favipiravir is a new drug designated for the treatment of the Ebola virus.
This deal value was converted from RMB at a rate of $US0.163 on 17 October 2014. [1]
Key Development Milestones
In early February 2020, Sihuan Pharmaceutical Holdings Group initiated clinical trials for favipiravir tablet for COVID-2019 infections.The trials were officially initiated by the Ministry of Science and Technology. The Human Genetic Resources Management Office of the PRC urgently reviewed the Trials and the Group obtained the human genetic resources administrative license in only one working day (2020GH0006YJ). The Trials are random, parallel dose exploration studies with three dosage groups (high, middle and low dosage) to explore the best treatment regimen of Favipiravir for COVID-19 patients. A total of 60 cases of regular COVID-19 patients are planned to be recruited for a treatment period of 10 days [2] .
Favipiravir received "Army Special Needs Drug Approval" from the People’s Liberation Army General Medical Department in August 2014 and is available for the emergency treatment of Ebola haemorrhagic fever [3] . Media reports state that doses of the drug have been sent to Africa to fight the 2014 Ebola virus infections, by the Chinese government.
Drug Properties & Chemical Synopsis
- Route of administration PO
- Formulation Tablet, unspecified
- Class Small molecules
- Target RNA; RNA replicase
- Mechanism of Action RNA inhibitors; RNA replicase inhibitors
-
WHO ATC code
J05A-X (Other antivirals)
-
EPhMRA code
J5B9 (Antivirals, others)
- Chemical name 6-Fluoro-3-hydroxy-2-pyrazinecarboxamide
- Molecular formula C5 H4 F N3 O2
- SMILES C1(C(=NC=C(N=1)F)O)C(=O)N
-
Chemical Structure
- CAS Registry Number 259793-96-9
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| Favipiravir - Sihuan Pharmaceutical Holdings Group | ACE2 | Outcome Measure |
| Alkaline phosphatase (ALPL) | Outcome Measure | |
| ALT | Outcome Measure | |
| B-lymphocyte antigen CD19 | Outcome Measure | |
| Bilirubin | Outcome Measure | |
| BNP | Detailed Description, Outcome Measure | |
| C-C chemokine receptor type 5 (CCR5) | Detailed Description, Outcome Measure | |
| C-C motif chemokine 4 (CCL4 | Outcome Measure | |
| C-C motif chemokine 5 (CCL5 | Detailed Description, Outcome Measure | |
| C-C motif chemokine 7 (CCL7 | Detailed Description, Outcome Measure | |
| C-C motif chemokine receptor 2 | Outcome Measure | |
| C-reactive protein (CRP) | Brief Summary, Detailed Description, Eligibility Criteria, Outcome Measure | |
| C-X-C motif chemokine receptor 3 | Outcome Measure | |
| C-X-C motif chemokine receptor 5 | Outcome Measure | |
| Cardiac Troponin I | Eligibility Criteria, Outcome Measure | |
| Cardiac Troponin T | Outcome Measure | |
| CD107a | Outcome Measure | |
| CD25 (IL2RA) | Outcome Measure | |
| CD3 gamma chain (CD3G) | Outcome Measure | |
| CD38 | Outcome Measure | |
| CD40/TNFRSF5 | Outcome Measure | |
| CD56 | Outcome Measure | |
| CD83 molecule | Outcome Measure | |
| CD86 molecule | Outcome Measure | |
| CD95 (APO-1/Fas) | Outcome Measure | |
| chemokine (C-C motif) receptor 6 | Outcome Measure | |
| chemokine (C-C motif) receptor 7 | Outcome Measure | |
| Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10) | Detailed Description, Outcome Measure | |
| Creatine | Eligibility Criteria, Outcome Measure | |
| CX3CR1 | Outcome Measure | |
| CXCR1 | Outcome Measure | |
| CYP3A4 | Arm Group Description, Detailed Description, Outcome Measure | |
| D-dimer | Detailed Description, Outcome Measure | |
| D-Galactose | Eligibility Criteria | |
| Fc fragment of IgG, low affinity IIIb, receptor (CD16b) | Outcome Measure | |
| Fc gamma RIIIa | Outcome Measure | |
| Ferritin | Brief Summary, Detailed Description, Outcome Measure | |
| Fibrinogen | Outcome Measure | |
| FSH | Eligibility Criteria | |
| gamma-glutamyltransferase 2 | Outcome Measure | |
| gamma-glutamyltransferase light chain 3 | Outcome Measure | |
| GGT | Outcome Measure | |
| GGTLC4P | Outcome Measure | |
| GGTLC5P | Outcome Measure | |
| Granulocyte-macrophage colony-stimulating factor (GM-CSF) | Outcome Measure | |
| GZMB | Outcome Measure | |
| HLA-DR | Outcome Measure | |
| IFN-alpha 2 | Arm Group Description | |
| Interleukin 1 Beta (IL-1β) | Detailed Description, Outcome Measure | |
| interleukin 3 receptor, alpha (low affinity) | Outcome Measure | |
| interleukin 6 receptor | Outcome Measure | |
| interleukin 7 receptor | Outcome Measure | |
| Interleukin-10 (IL-10) | Outcome Measure | |
| Interleukin-6 (IL-6) | Detailed Description, Outcome Measure | |
| L-Serine | Outcome Measure | |
| MDR1 | Arm Group Description, Outcome Measure | |
| MIP-1 alpha | Detailed Description, Outcome Measure | |
| Monocyte chemoattractant protein-1 (MCP-1/CCL2) | Outcome Measure | |
| N-Acetyl-L-aspartic acid | Eligibility Criteria | |
| PD-1/CD279 | Outcome Measure | |
| perforin 1 (pore forming protein) | Outcome Measure | |
| phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha | Outcome Measure | |
| seryl-tRNA synthetase | Detailed Description | |
| sucrase-isomaltase | Eligibility Criteria | |
| T-Cell differentiation antigen CD8 | Outcome Measure | |
| T-cell receptor CD3-epsilon (CD3e) | Outcome Measure | |
| T-cell receptor T3 delta chain (CD3d) | Outcome Measure | |
| T-cell surface antigen CD4 | Outcome Measure | |
| TLX1 neighbor | Outcome Measure | |
| transmembrane protease, serine 2 | Outcome Measure | |
| Tumor necrosis factor alpha (TNF-alpha) | Detailed Description, Outcome Measure | |
| Uric acid | Eligibility Criteria, Outcome Measure | |
| Vascular endothelial growth factor A (VEGF) | Detailed Description, Outcome Measure | |
| Xanthine | Eligibility Criteria |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Bunyavirus infections | - | - | No development reported (Preclinical) | China | unspecified / unspecified | Sihuan Pharmaceutical Holdings Group | 28 Nov 2018 |
| COVID 2019 infections | - | - | No development reported (Clinical) | China | PO / Tablet | Sihuan Pharmaceutical Holdings Group | 28 Mar 2023 |
| Ebola virus infections | - | - | No development reported (Clinical) | China | unspecified / unspecified | Sihuan Pharmaceutical Holdings Group | 04 Nov 2017 |
| Influenza virus infections | - | - | No development reported (Preclinical) | China | unspecified / unspecified | Sihuan Pharmaceutical Holdings Group | 28 Nov 2018 |
| Viral haemorrhagic fevers | - | - | No development reported (Preclinical) | China | unspecified / unspecified | Sihuan Pharmaceutical Holdings Group | 28 Nov 2018 |
| Yellow fever | - | - | No development reported (Preclinical) | China | unspecified / unspecified | Sihuan Pharmaceutical Holdings Group | 28 Nov 2018 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Academy of Military Medical Sciences | Originator | China |
| Sihuan Pharmaceutical Holdings Group | Owner | Hong-Kong |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 28 Mar 2023 | Phase Change - No development reported | No recent reports of development identified for clinical-Phase-Unknown development in COVID-2019-infections in China (PO, Tablet) Updated 28 Mar 2023 |
| 12 Jan 2022 | Biomarker Update | Biomarkers information updated Updated 14 Jan 2022 |
| 12 Mar 2020 | Other | Chemical structure information added Updated 12 Mar 2020 |
| 15 Feb 2020 | Phase Change - Clinical | Clinical trials in COVID-2019 infections in China (PO) in early February 2020 [2] Updated 09 Mar 2020 |
| 28 Nov 2018 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Bunyavirus-infections in China Updated 28 Nov 2018 |
| 28 Nov 2018 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Influenza-virus-infections in China Updated 28 Nov 2018 |
| 28 Nov 2018 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Viral-haemorrhagic-fevers in China Updated 28 Nov 2018 |
| 28 Nov 2018 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Yellow-fever in China Updated 28 Nov 2018 |
| 04 Nov 2017 | Phase Change - No development reported | No recent reports of development identified for clinical-Phase-Unknown development in Ebola-virus-infections in China Updated 04 Nov 2017 |
| 06 Oct 2014 | Licensing Status | Sichuan Pharma acquires jk 05 from the Academy of Military Medical Sciences [1] Updated 21 Oct 2014 |
| 06 Oct 2014 | Phase Change - Preclinical | Preclinical trials in Bunyavirus infections, Influenza virus infections, Viral haemorrhagic fevers, Yellow fever in China (unspecified route) Updated 21 Oct 2014 |
| 29 Aug 2014 | Phase Change - Clinical | Clinical trials in Ebola virus infections in China (unspecified route) Updated 21 Oct 2014 |
| 29 Aug 2014 | Regulatory Status | The General Logistics Department of People’s Liberation Army approves jk 05 for the emergency treatment of Ebola virus infections [3] Updated 21 Oct 2014 |
References
-
Collaboration Agreement with Academy of Military Medical Sciences for Development of Anti-Ebola Drug jk-05.
Media Release -
Sihuan Pharmaceutical Announces Clinical Research of Favipiravir, A Drug for Coronavirus Disease 2019, Co-Developed with the Academy of Military Medical Sciences of the People's Liberation Army, Has Commenced.
Media Release -
China Approves its First Anti-Ebola Drug.
Media Release
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