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704260009

Refrigerated Storage

CyramzaEli Lilly

Eli Lilly
Cyramza
10 mg/ml concentrate for solution for infusion

Contact Eli Lilly in all cases where a deviation from the recommended storage conditions has occurred. Refer to the current BNF for company contact details.

21 May 2019
London MI Service

New Medicines

CyramzaHepatocellular carcinoma (HCC) and elevated baseline alpha-fetoprotein - second-line after sorafenib

Information

Cyramza
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

Launched
Launched
Launched
September 2019
Yes
Sep 19Approved in EU [18].
Jun 19Recommended for EU approval by CHMP - the additional indication is "for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma who have a serum alpha fetoprotein (AFP) of ≥ 400 ng/ml and who have been previously treated with sorafenib” [17].
May 19Approved by FDA as a single agent for the 2nd line treatment of pts with HCC with elevated AFP who have previously been treated with sorafenib [15].
Dec 18Lilly has decided not to proceed with commercial launch for this indication in the UK [13].
Dec 18Filed in the US [12].
Apr 18Filings to start mid 2018 [11].
Feb 16Withdrawn from the EU Community Register of designated Orphan Medicinal Products medicinal products on request of the Sponsor [9].
Nov 13EU filing will be via the centralised procedure [4].
Jul 12Granted orphan drug status in EU for hepatocellular carcinoma. It also has orphan drug status in the US [2].

Category

Vascular endothelial growth factor receptor-2 antagonist
The age-standardised incidence rate for liver cancer in the UK in 2008 was 4.3 per 100,000 population
Hepatocellular carcinoma (HCC) and elevated baseline alpha-fetoprotein - second-line after sorafenib
Intravenous

Further information

Yes
October 2019

Trial or other data

May 19Approved by FDA as a single agent for the 2nd line treatment of pts with HCC with elevated AFP who have previously been treated with sorafenib [15].
Jan 19Results of the PIII REACH-2 study (NCT02435433) (n= 292) published in the Lancet. The reported improved survival at median follow-up of 7.6 months with ramucirumab vs placebo (8.5 vs 7.3 months; HR, 0.710; p=0.0199) in patients with hepatocellular carcinoma and α-fetoprotein concentrations of at least 400 ng/mL who had previously received sorafenib [14].
Apr 18Eli Lilly announces Cyramza significantly extended overall survival and progression-free survival vs. placebo in patients with high levels of the glycoprotein alpha-fetoprotein (AFP), a biomarker the company called a marker of poor prognosis. It is the first medicine to put up positive liver cancer results in a biomarker-selected population [11].
Dec 17PIII REACH-2 study (NCT02435433) is still recruiting & expects to complete collection of primary outcome data in Jan 18 [10].
Jan 17NCT02435433 Estimated Primary Completion Date: October 2017
Jun 15PIII REACH-2 study (NCT02435433) is due to complete collection of primary outcome data in Oct 2017. It will enrol 399 pts [8].
Jun 15Eli Lilly plans to initiate the PIII REACH-2 trial to evaluate the safety and efficacy of ramucirumab and best supportive care (BSC) compared with placebo and BSC in patients with hepatocellular carcinoma and elevated baseline alpha-fetoprotein (NCT02435433). The primary endpoint is overall survival, assessed at 28 months. The randomised, double-blind trial was designed to enrol approximately 399 patients in the US, the UK, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, France, Germany, Hong Kong, Israel, Italy, Japan, Poland, South Korea, Spain, Switzerland, Taiwan [7].
Jun 15Results of REACH study published in The Lancet Oncology. This trial (n=565) found that second-line treatment with ramicirumab, did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma (9.2 vs. 7.6 months placebo, p=0.14) [6].
Jun 14PIII REACH trial of CYRAMZA in pts with hepatocellular carcinoma did not meet its primary endpoint; overall survival favored the CYRAMZA arm but was not statistically significant [5].
Mar 14PIII NCT01140347 study is ongoing but no longer recruiting pts. Collection of primary outcome data is complete [3].
Jul 12NCT01140347 (REACH): is a multicentre, randomized, double-blind, PIII study of ramucirumab (8 mg/kg IV every 2 weeks) and best supportive care (BSC) vs placebo and BSC as second-line treatment in 544 patients with hepatocellular carcinoma following first-line therapy with sorafenib. Treatment will be continued until radiographic or symptomatic progression, development of unacceptable toxicity, noncompliance or withdrawal of consent by the patient, or investigator decision. The primary outcome is overall survival. The study started Oct 10 and is due to complete Aug 13 [1].

Evidence based evaluations

CyramzaNon-small cell lung cancer (NSCLC), EGFR mutation-positive metastatic - first-line in combination with erlotinib

Information

Cyramza
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

Launched
Launched
Launched
January 2020
May 20Approved in the US [11]
Feb 20FDA advisers voted 6-5 in favour of approval of ramucirumab plus erlotinib in previously untreated EGFR-positive NSCLC [10].
Jan 20Approved in the EU [9].
Dec 19Recommended for EU approval by CHMP - the additional indication is "in combination with erlotinib ... for the first-line treatment of adult patients with metastatic non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutations (see section 5.1).” [8].
Nov 19Currently pre-registration in the EU. Has been filed via the centralised procedure [7].

Category

Vascular endothelial growth factor receptor-2 antagonist
There were 46,403 new cases diagnosed in the UK in 2014 [1]. Non-small cell lung carcinoma (NSCLC) is the most common type accounting for around 80% of lung cancers. Prevalence of EGFR-TK mutations in NSCLC (adenocarcinoma) ranges from 10.4% in an Italian study, to 50% and 39% in Japanese and Taiwanese studies [2].
Non-small cell lung cancer (NSCLC), EGFR mutation-positive metastatic - first-line in combination with erlotinib
Intravenous

Further information

Yes
Suspended

Trial or other data

Oct 19PIII RELAY RCT (n=449) is published; it reports that ramucirumab plus erlotinib demonstrated superior progression-free survival versus placebo plus erlotinib at a median of 20.7 months follow up (19.4 vs 12.4 months; HR 0.59; 95% CI 0.46–0.76; p<0.0001) [6].
Mar 19Lilly announce PIII RELAY trial met primary endpoint, significantly improving PFS in first-line treatment of metastatic EGFR-mutated NSCLC [5].
Dec 18PIII RELAY trial has finished recruiting and expects to complete collection of primary outcome data in Jan 19 [4].
Feb 18PIII RELAY trial is still recruiting and expects to complete collection of primary outcome data in Oct 18 [3].
May 15PIII RELAY study to evaluate safety and efficacy of ramucirumab, in combination with erlotinib compared to placebo in patients with EGFR mutation-positive metastatic NSCLC starts (NCT02411448). The randomised, double-blind trial intends to enrol approximately 462 patients in Spain, Canada, the US, the UK, Germany, France, Hong Kong, Italy, Japan, South Korea and Taiwan. Primary outcome is PFS and adverse effects [3].

Evidence based evaluations

CyramzaLocally advanced, unresectable or metastatic urothelial (transitional cell) carcinoma of the bladder, urethra, ureter, or renal pelvis - second-line after platinum chemotherapy

Information

Cyramza
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Jan 20Indication not listed in global company pipeline; assume all development discontinued [7].
Sep 18EU development discontinued due to lack of a statistically significant OS benefit in RANGE study [6].

Category

Vascular endothelial growth factor receptor-2 antagonist
UK incidence of bladder cancer is 11.4 per 100,000 population. The vast majority of bladder cancers in the UK are transitional cell carcinomas (also known as urothelial cell carcinomas). The recurrence rate for superficial transitional cell cancer of the bladder is high (70% within five years). As many as 80% of pts have at least one recurrence [3].
Locally advanced, unresectable or metastatic urothelial (transitional cell) carcinoma of the bladder, urethra, ureter, or renal pelvis - second-line after platinum chemotherapy
Intravenous