Ramucirumab
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | VEGFR2 (KDR) |
| Clinical data | |
| Trade names | Cyramza |
| AHFS/Drugs.com | cyramza |
| License data | |
| Routes of administration | Intravenous infusion |
| ATC code | |
| Legal status | |
| Legal status |
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| Pharmacokinetic data | |
| Metabolism | Probably proteases |
| Elimination half-life | 14 days |
| Identifiers | |
| CAS Number | |
| ChemSpider |
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| UNII | |
| Chemical and physical data | |
| Formula | C6374H9864N1692O1996S46 |
| Molar mass | 143.6 kg/mol g·mol−1 |
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Ramucirumab[1] (LY3009806, IMC-1121B, trade name Cyramza[2][3]) is a fully human monoclonal antibody (IgG1) developed for the treatment of solid tumors. This drug was developed by ImClone Systems Inc. It was isolated from a native phage display library from Dyax.
Approved uses
On 21 April 2014, the US Food and Drug Administration (FDA) approved ramucirumab, as a single agent or with paclitaxel, for treatment of advanced gastric or gastro-esophageal junction adenocarcinoma if the disease has progressed despite fluoropyrimidine- or platinum-containing chemotherapy.[4][5]
On 12 December 2014, the FDA approved ramucirumab in combination with docetaxel, for treatment of metastatic non-small-cell lung carcinoma (NSCLC) with disease progression on or after platinum-containing chemotherapy. If the cancer has a sensitizing mutation of EGFR or ALK previous therapy should have included targeted therapy for the genomic tumor aberration.[6]
In Europe, the drug is approved since 21 January 2015 for gastric or gastro-esophageal junction cancer under the same conditions. Meanwhile, it has also been approved for NSCLC, as well as in combination with FOLFIRI for the treatment of metastatic colorectal cancer if the disease has progressed despite bevacizumab, oxaliplatin and capecitabine (or similar) therapy.[7][8]
Contraindications
Under the European approval, NSCLC therapy with ramucirumab is contraindicated when there is tumour cavitation, or if major vessels are involved.[7][9]
Side effects
The most common adverse effects in a study investigating ramucirumab monotherapy were diarrhoea (14% of patients, as compared to 9% under placebo), hyponatraemia (low blood sodium levels; 6% versus 2%), headache (9% versus 3%), and high blood pressure (16% versus 8%).[10]
Interactions
In studies, no interactions were observed with paclitaxel, docetaxel or irinotecan.[7][10]
Pharmacology
Mechanism of action
It is directed against the vascular endothelial growth factor receptor 2 (VEGFR2). By binding to VEGFR2 it works as a receptor antagonist blocking the binding of vascular endothelial growth factor (VEGF) to VEGFR2. VEGFR2 is known to mediate the majority of the downstream effects of VEGF in angiogenesis.[11]
Clinical trials
On September 26, 2013 the manufacturer Eli Lilly announced that its Phase III study for ramucirumab failed to hit its primary endpoint on progression-free survival among women with metastatic breast cancer.[12][13]
In June 2014, a phase III trial of the drug reported it failed to improve overall survival in liver cancer.[14]
In Feb 2016 it was reported that a phase II trial of adding ramucirumab to docetaxel improved progression-free survival (PFS) compared with docetaxel alone in locally advanced or metastatic urothelial carcinoma.[15] It is now in the RANGE phase III trial for this indication.[16]
References
- ^ Statement On A Nonproprietary Name Adopted By The USAN Council - Ramucirumab, American Medical Association.
- ^ FierceBiotech: FDA OKs Lilly's blockbuster hopeful ramucirumab for stomach cancer
- ^ Cyramza official website
- ^ FDA.gov press release for ramucirumab approval, accessed April 22, 2014
- ^ Ramucirumab gastric cancer regimen & reference
- ^ [1]
- ^ a b c "Cyramza: EPAR – Product Information" (PDF). European Medicines Agency. 21 January 2015.
- ^ "Cyramza: EPAR – Public assessment report" (PDF). European Medicines Agency. 22 January 2015.
- ^ Haberfeld, H, ed. (2017). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Cyramza 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung.
- ^ a b FDA Professional Drug Information on Cyramza.
- ^ Ramucirumab (Cyramza) package insert
- ^ Clinical trial number NCT00703326 for "Phase III Study of Docetaxel + Ramucirumab or Placebo in Breast Cancer" at ClinicalTrials.gov
- ^ Fierce Biotech. "In another stinging setback, Eli Lilly's ramucirumab fails PhIII breast cancer study". Retrieved 27 September 2013.
- ^ http://www.genengnews.com/gen-news-highlights/lilly-s-cyramza-fails-phase-iii-trial-in-liver-cancer/81249964/
- ^ Ramucirumab Added to Docetaxel Extends PFS in Urothelial Carcinoma.Feb 2016
- ^ A Study of Ramucirumab (LY3009806) Plus Docetaxel in Participants With Urothelial Cancer (RANGE)