Overview
Ruxolitinib, formerly known as INCB018424 or INC424, is an anticancer drug and a Janus kinase (JAK) inhibitor. It is a potent and selective inhibitor of JAK1 and JAK2, which are tyrosine kinases involved in cytokine signalling and hematopoiesis. Myeloproliferative neoplasms, such as myelofibrosis and polycythemia vera, are often characterized by aberrant activation of the JAK-STAT pathway, leading to abnormal blood cell counts and thrombotic complications. By inhibiting JAK1 and JAK2, ruxolitinib works to block the dysregulated cell signalling pathways and prevents abnormal blood cell proliferation. Due to a large number of patients with myeloproliferative neoplasms who have JAK2 mutations, ruxolitinib was the first ATP-competitive inhibitor of JAK1 and JAK2 ever developed. Ruxolitinib was first approved for the treatment of adult patients with myelofibrosis by the FDA in 2011, followed by EMA's approval in 2012. In 2014, it was approved for the treatment of polycythemia vera in adults who have an inadequate response to or are intolerant of hydroxyurea and in 2019, ruxolitinib was approved for use in steroid-refractory acute graft-versus-host disease in adults and children. The topical formulation of ruxolitinib is used to treat atopic dermatitis and vitiligo. It is being investigated for other inflammatory skin conditions. Ruxolitinib has been investigated to treat patients with coronavirus disease 2019 (COVID-19) accompanied by severe systemic hyperinflammation. In phase II clinical trials, ruxolitinib improved chest computed tomography and improved recovery in patients with lymphopenia. However, phase III clinical trials later determined that ruxolitinib was inadequate in meeting its primary endpoint of reducing the number of hospitalized COVID-19 patients who experienced severe complications thus the drug was not approved as a treatment for COVID-19.
Indication
Ruxolitinib is indicated for the treatment of the following conditions: Topical ruxolitinib is indicated for:
Associated Conditions
- Acute Graft-Versus-Host Disease (GVHD)
- Chronic Graft-Versus-Host Disease
- Non-segmental Vitiligo
- Post Polycythemia Vera Myelofibrosis
- Post-essential Thrombocythemia Myelofibrosis (Post-ET MF)
- Primary Myelofibrosis (PMF)
- High risk Myelofibrosis
- Intermediate risk Myelofibrosis
- Mild Atopic dermatitis
- Moderate Atopic dermatitis
- Refractory Polycythemia vera
Research Report
Ruxolitinib: A Comprehensive Monograph on a First-in-Class JAK1/2 Inhibitor
Executive Summary
Ruxolitinib represents a landmark achievement in targeted therapy, establishing a new class of medication as the first orally bioavailable small molecule inhibitor of Janus-associated kinases (JAK) 1 and 2 to receive regulatory approval. Initially developed under the code INCB018424, Ruxolitinib has fundamentally altered the therapeutic landscape for patients with myeloproliferative neoplasms (MPNs), offering the first effective treatment for the debilitating splenomegaly and constitutional symptoms associated with intermediate and high-risk myelofibrosis (MF). Its mechanism, which involves the potent and selective inhibition of the JAK-STAT signaling pathway, directly targets the core pathophysiology of these disorders.
The drug's clinical utility has rapidly expanded beyond its initial indication. It is now a standard second-line therapy for polycythemia vera (PV) in patients who are intolerant of or refractory to hydroxyurea. Furthermore, Ruxolitinib has proven to be a critical, life-saving intervention for both adult and pediatric patients with steroid-refractory acute and chronic graft-versus-host disease (GVHD), a severe complication of allogeneic stem cell transplantation for which few effective treatments previously existed.
Demonstrating remarkable versatility, Ruxolitinib has been successfully reformulated as a 1.5% topical cream (Opzelura®) for the treatment of non-segmental vitiligo and atopic dermatitis, extending its immunomodulatory benefits to the field of dermatology. This dual-formulation success underscores the broad applicability of targeting the JAK-STAT pathway in diseases driven by inflammation and immune dysregulation.
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
---|---|---|---|---|---|
2025/07/03 | Not Applicable | Not yet recruiting | |||
2025/06/24 | Phase 2 | Not yet recruiting | |||
2025/06/17 | Phase 1 | Not yet recruiting | City of Hope Medical Center | ||
2025/05/25 | Phase 2 | Not yet recruiting | Baptist Health South Florida | ||
2025/05/15 | Phase 2 | Not yet recruiting | |||
2025/05/06 | Phase 3 | Recruiting | |||
2025/05/06 | Phase 3 | Recruiting | |||
2025/04/20 | Phase 2 | Recruiting | John Levine | ||
2025/04/11 | Phase 2 | Not yet recruiting | |||
2025/03/04 | Phase 2 | Not yet recruiting |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
---|---|---|---|---|---|
Incyte Corporation | 50881-015 | ORAL | 15.0 mg in 1 1 | 1/31/2023 | |
Incyte Corporation | 50881-007 | TOPICAL | 15 mg in 1 g | 9/20/2023 | |
Incyte Corporation | 50881-010 | ORAL | 10.0 mg in 1 1 | 1/31/2023 | |
Incyte Corporation | 50881-020 | ORAL | 20.0 mg in 1 1 | 1/31/2023 | |
Incyte Corporation | 50881-005 | ORAL | 5.0 mg in 1 1 | 1/31/2023 | |
Incyte Corporation | 50881-025 | ORAL | 25.0 mg in 1 1 | 1/31/2023 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
---|---|---|---|
Authorised | 4/19/2023 | ||
Authorised | 8/23/2012 |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
---|---|---|---|---|---|
JAKAVI TABLET 15MG | SIN14397P | TABLET | 15mg | 8/22/2013 | |
JAKAVI TABLET 10MG | SIN14927P | TABLET | 10mg | 1/25/2016 | |
JAKAVI TABLET 5MG | SIN14396P | TABLET | 5mg | 8/22/2013 | |
JAKAVI TABLET 20MG | SIN14398P | TABLET | 20mg | 8/22/2013 |
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
---|---|---|---|---|---|
Ruxolitinib Phosphate Tablets | 国药准字H20249398 | 化学药品 | 片剂 | 11/15/2024 | |
Ruxolitinib Phosphate Tablets | 国药准字HJ20170127 | 化学药品 | 片剂 | 12/7/2021 | |
Ruxolitinib Phosphate Tablets | 国药准字HJ20170129 | 化学药品 | 片剂 | 12/7/2021 | |
Ruxolitinib Phosphate Tablets | 国药准字HJ20170130 | 化学药品 | 片剂 | 12/7/2021 | |
Ruxolitinib Phosphate Tablets | 国药准字HJ20170128 | 化学药品 | 片剂 | 12/7/2021 | |
Ruxolitinib Phosphate Tablets | 国药准字HJ20170134 | 化学药品 | 片剂 | 12/7/2021 | |
Ruxolitinib Phosphate Tablets | 国药准字HJ20170133 | 化学药品 | 片剂 | 12/7/2021 |
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
---|---|---|---|---|---|
No PPB approvals found for this drug. |
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
---|---|---|---|---|---|
JAKAVI ruxolitinib (as phosphate) 15 mg tablet blister pack | 198936 | Medicine | A | 7/3/2013 | |
JAKAVI ruxolitinib (as phosphate) 20 mg tablet blister pack | 198933 | Medicine | A | 7/3/2013 | |
JAKAVI ruxolitinib (as phosphate) 5 mg tablet blister pack | 198934 | Medicine | A | 7/3/2013 | |
JAKAVI ruxolitinib (as phosphate) 10 mg tablet blister pack | 232702 | Medicine | A | 12/16/2015 |
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