Cyramza (ramucirumab) is a human monoclonal antibody indicated for the treatment of Gastric cancer. Cyramza molecule was originally discovered by ImClone Systems, which was later acquired by Eli Lilly and Company in 2008.
Cyramza is the first FDA-approved treatment for gastric cancer after prior chemotherapy. Eli Lilly received approval for Cyramza from the US Food and Drug Administration (FDA) for as a single-agent treatment for patients with advanced or metastatic gastric cancer or adenocarcinoma of the gastroesophageal junction (GEJ) in April 2014. The US FDA also granted orphan designation to the drug.
Gastric cancer treatment
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An oral anti-cancer agent that blocks cell proliferation and tumour angiogenesis.
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Also known as stomach cancer or adenocarcinoma, gastric cancer originates in the form of a malignant tumour in the lining of stomach. In its advanced stages, the disease travels through the bloodstream and reaches organs such as liver, lungs and bones. It is the fifth most common cancer and the third-leading cause of cancer death in the world.
Around a million new gastric cancer cases were registered worldwide in 2012. The disease is preva lent outside the US and in the European Union (EU).
Cyramza blocks VEGF receptor 2
Cyramza is a human monoclonal antibody (IgG1) that binds and blocks the activation of vascular endothelial growth factor (VEGF) receptor 2. The drug also stops binding of VEGF receptor ligands VEGF-A, VEGF-C and VEGF-D.
The drug is available in 500mg/50ml and 100mg/10ml dosed vials for injection.
Clinical trials on Cyramza
The FDA approval for Cyramza was based on the results obtained from a phase III clinical trial known as REGARD study. The randomised, double-blinded and placebo-controlled study enrolled 355 patients across 29 countries. Patients enrolled in the study had locally advanced or metastatic gastric cancer, including gastroesophageal junction adenocarcinoma following progression after initial fluoropyrimidine or platinum-containing chemotherapy.
"Patients enrolled for the study had locally advanced or metastatic gastric cancer, including gastroesophageal junction adenocarcinoma following progression after initial fluoropyrimidine or platinum-containing chemotherapy."
Patients were administered with Cyramza solution and best supportive care (BSC) compared with placebo plus BSC. The primary endpoint of the study was overall survival and the secondary outcome measure was progression-free survival.
The results of the study demonstrated that patients given Cyramza 8mg/kg by infusion every two weeks and best supportive care (BSC), as compared with placebo and BSC, showed improved overall survival and progression-free survival. The Cyramza 8mg/kg by infusion plus best supportive care (BSC) group also witnessed an increase in the median overall survival of patients with advanced gastric cancer by 37%.
The overall median survival in Cyramza 8mg/kg plus best supportive care (BSC) arm was 5.2 months compared with 3.8 months in placebo arm and 0.78 in hazard ratio group. The progression-free survival was 2.1 months in Cyramza 8mg/kg plus BSC patients compared with 1.3 months in placebo and 0.48 months in hazard ratio.
The adverse reactions found in the Cyramza-administered patients during the clinical study included hypertension and diarrhoea.
Marketing commentary
Eli Lilly and Company, headquartered at Indianapolis, US, is engaged in the discovery, development and commercialisation of high-quality medicines. It has 13 manufacturing plants and around 38,000 employees across 55 countries, and markets products in more than 125 countries.
美国药监局批准礼来Cyramza用于治疗胃癌？药监局于4月21日批准礼来研发的单抗药物Cyramza（ramucirumab）用于治疗晚期胃癌和胃食管连接部腺癌，证实能有效延长患者生命，减缓肿瘤生长。胃癌形成于胃部内层组织，多发于老年人。根据美国国家癌症研究所统计，今年约有22220美国人被诊断出胃癌，10990美国人会死于这种疾病。
Cyramza是一种血管再生抑制剂，能阻断肿瘤的血液供给，适用于已使用氟嘧啶和含铂药物后不能手术切除或癌细胞已转移的病人。药监局药品评价与研究中心血液与肿瘤办公室负责人，医学博士RichardPazdur表示，虽然在过去的40年中，美国胃癌的发生率有所下降，但患者仍然需要新的治疗选择，尤其是那些对其它疗法均无效的患者。
研究人员征集了355位不能手术切除或转移性的胃癌和胃食管连接部腺癌患者进行临床试验，评价Cyramza的安全性和有效性。2/3的受试者为Cyramza组，其余受试者为安慰剂组，然后研究人员观察患者的生存时间（总生存率）。
试验结果表明，Cyramza组患者的中位生存率为5.2个月，而安慰剂组只有3.8个月。此外，与安慰机组比较，服用Cyramza的患者能减缓肿瘤生长，即延长癌症无进展生存期。故Cyramza被证实能延长患者生命，减缓肿瘤生长。同时，研究人员也开展了另一项临床试验，评估Cyramza与紫杉醇联合使用的有效性。试验结果表明，两种药物的联合使用比单用紫杉醇更能延长患者的总生存率。在临床试验中，Cyramza常见的副作用包括腹泻和高血压。药监局曾授予Cyramza优先审评资格，属于孤儿药，用于治疗罕见疾病。
Information
Generic Name: ramucirumab
Trade Name: Cyramza
Synonym: IMC 1121B
Entry Type: New molecular entity
Developmental Status
UK: Pre-registration (Filed)
EU: Pre-registration (Filed)
US: Approved (Licensed)
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
April 14: Approved by US FDA to treat patients with advanced stomach cancer or gastroesophageal junction adenocarcinoma. [12]
22/04/2014 08:18:54
Oct 13: Filed in the EU as a single-agent treatment for advanced gastric cancer following disease progression after initial chemotherapy [11].
07/01/2014 10:16:17
On 4 July 2012, orphan designation (EU/3/12/1004) was granted in the EU for ramucirumab for the treatment of gastric cancer [11].
24/10/2013 09:01:03
Oct 13: The FDA has granted Priority Review to the regulatory submission for ramucirumab as a single-agent treatment for advanced gastric cancer following disease progression after initial chemotherapy. The filing is based on data from REGARD. A US decision on approval is expected 2Q 2014. It has also been filed in the EU [10].
24/10/2013 08:43:26
April 12: PIII trials in progress, anticipated EU filing date later than 2012
13/04/2012 08:52:45
EU filing anticipiated 2012 (2)
19/01/2010 16:28:09
Trial or other data
Oct 13: REGARD study published in The Lancet [9].
04/10/2013 10:34:50
Sep 13: Top line results reported from the global PIII RAINBOW trial of ramucirumab + paclitaxel vs paclitaxel + placebo in patients with advanced gastric cancer refractory to or progressive after initial chemotherapy. The study met its primary endpoint of improved overall survival and a secondary endpoint of improved progression-free survival. The most common (>5% incidence) Grade >3 adverse events occurring at a higher rate on the ramucirumab arm included neutropenia, leukopenia, hypertension, fatigue/asthenia and abdominal pain [8].
26/09/2013 22:18:20
Jan 13: Further results from REGARD study presented at ASCO. Ramucirumab met its primary goal of improving overall survival (5.2 months vs 3.8 months with placebo). PFS was 2.1 vs 1.3 months, respectively. The company may file in the US later this year [7].
24/01/2013 15:45:33
Oct 12: Company report that the PIII REGARD trial , in patients with metastatic gastric cancer, met its primary endpoint of improved overall survival and also showed prolonged progression-free survival. The REGARD trial compared ramucirumab and best supportive care vs placebo and best supportive care as a second-line treatment in patients with metastatic gastric and gastroesophageal junction cancers. The most frequent adverse reaction (any grade) occurring at a higher rate with ramucirumab was hypertension (12%); other AEs ( > 5%) occurring more often with ramucirumab were diarrhoea and headache. A second PIII study in gastric cancer. RAINBOW, of ramucirumab in combination with paclitaxel, completed patient enrollment Sep 12 [6].
16/10/2012 09:15:52
Feb 12: Phase III trial eva luating the overall survival of patients with metastatic gastric cancer (NCT00917384). The 355 patients enrolled have all experienced disease progression following first-line platinum- or fluoropyrimidine-containing combination chemotherapy. Comparisons will be made between ramucirumab + best supportive care (BSC) and placebo + BSC. [4]
13/04/2012 08:46:50
Oct 10: A PIII trial (NCT01170663) eva luating the safety & efficacy of ramucirumab in combination with paclitaxel as second-line therapy began recruitment of approx 663 pts with metastatic gastric or gastro-oesophageal junction adenocarcinoma. Trial sites include the US, Germany, Singapore, Spain & Taiwan. The primary outcome measure will be overall survival time [3].
11/04/2011 11:26:03
NCT00917384: Started in Jul 09, this PIII study will eva luate the overall survival (OS) of 615 patients with metastatic gastric cancer (and gastroesophageal junction) following disease progression on first-line platinum- or fluoropyrimidine-containing combination chemotherapy who undergo treatment with the IMC-1121B plus best supportive care (BSC) vs placebo plus BSC. IMC-112B will be administered by IV infusion every 2 weeks at a dose of 8 mg/kg. Estimated study completion date: November 2012 [1].
18/07/2009 16:56:05
Evidence Based eva luations
NHSC/NIHR http://www.hsc.nihr.ac.uk/topics/ramucirumab-monotherapy-for-advanced-gastric-cance/
Category
BNF Category: Other immunomodulating drugs (08.02.04)
Pharmacology: Vascular endothelial growth factor receptor-2 antagonist
Epidemiology: Gastric cancer is the second most common cause of cancer-related death in the world. It is a difficult disease to cure, mainly because most patients present with advanced disease. 50% involve the pylorus, 25% the lesser curve and 10% the cardia. 2-8% of gastric cancers are lymphomas. 95% of gastric cancers occur in those aged over 55 years. 4,923 new diagnoses of gastric cancer were made in the UK in 2008. [5]
Indication: Gastric cancer
Additional Details: or gastro-oesophageal junction cancer, second-line
Method(s) of Administration
Intravenous infusion
Company Information
Name: Eli Lilly
US Name: Eli Lilly
NICE Information
In timetable: No
When: |
