Zirabev
Registration timeline
The following table summarises the key steps and dates for this application.
| Description | Date |
|---|---|
| Submission dossier accepted and first round evaluation commenced | 31 October 2018 |
| First round evaluation completed | 5 April 2019 |
| Sponsor provides responses on questions raised in first round evaluation | 31 May 2019 |
| Second round evaluation completed | 22 July 2019 |
| Delegate's overall benefit-risk assessment | 11 September 2019 |
| Sponsor's pre-Advisory Committee response | Not applicable |
| Advisory Committee meeting | Not applicable |
| Registration decision (Outcome) | 28 October 2019 |
| Completion of administrative activities and registration on ARTG | 21 November 2019 |
| Number of working days from submission dossier acceptance to registration decision* | 211 |
*Statutory timeframe for standard applications is 255 working days
Metastatic colorectal cancer
The recommended dose of Zirabev, administered as an IV infusion, is as follows:
First-line treatment
5 mg/kg of body weight given once every 2 weeks or 7.5 mg/kg of body weight given once every 3 weeks.
Second-line treatment
10 mg/kg of body weight given every 2 weeks or 15 mg/kg of body weight given once every 3 weeks.
It is recommended that Zirabev treatment be continued until progression of the underlying disease.
Locally recurrent or metastatic breast cancer
The recommended dose of Zirabev is 10 mg/kg of body weight given once every 2 weeks or 15 mg/kg of body weight given once every 3 weeks as an IV infusion.
It is recommended that Zirabev treatment be continued until progression of the underlying disease.
Advanced, metastatic or recurrent non-squamous non-small cell lung cancer
The recommended dose of Zirabev in combination with carboplatin and paclitaxel is 15 mg/kg of body weight given once every 3 weeks as an IV infusion.
Zirabev is administered in addition to carboplatin and paclitaxel for up to 6 cycles of treatment followed by Zirabev as a single agent until disease progression.
Advanced and/or metastatic renal cell cancer
The recommended dose of is Zirabev 10 mg/kg given once every 2 weeks as an IV infusion. It is recommended that Zirabev treatment be continued until progression of the underlying disease.
Zirabev should be given in combination with IFN alfa-2a (Roferon-A). The recommended IFN alfa-2a dose is 9 MIU three times a week, however, if 9 MIU is not tolerated, the dosage may be reduced to 6 MIU and further to 3 MIU three times a week (see Section 5.1 Pharmacodynamic properties; Clinical trials). Please also refer to the Roferon-A Product Information.
Grade IV glioma
The recommended dose of Zirabev is 10 mg/kg of body weight given once every 2 weeks or 15 mg/kg of body weight given once every 3 weeks as an IV infusion.
It is recommended that Zirabev treatment be continued until progression of the underlying disease.
Epithelial ovarian, fallopian tube or primary peritoneal cancer
The recommended dose of Zirabev administered as an IV infusion is as follows:
First line treatment
15 mg/kg of body weight given once every 3 weeks in combination with carboplatin and paclitaxel for up to 6 cycles of treatment, followed by continued use of Zirabev as single agent.
It is recommended that Zirabev treatment be continued for a total of 15 months therapy or until disease progression, whichever occurs earlier.
Treatment of recurrent disease
- Platinum sensitive: 15 mg/kg of body weight given once every 3 weeks in combination with carboplatin and paclitaxel for 6 cycles (up to 8 cycles) followed by continued use of Zirabev as a single agent until disease progression. Alternatively, 15 mg/kg of body weight given once every 3 weeks in combination with carboplatin and gemcitabine for 6 cycles (up to 10 cycles), followed by continued use of Zirabev as single agent until disease progression.
- Platinum resistant: 10 mg/kg body weight given once every 2 weeks when administered in combination with one of the following agents - paclitaxel or topotecan (given weekly) or pegylated liposomal doxorubicin. Alternatively, 15 mg/kg every 3 weeks when administered in combination with topotecan given on days 1-5, every 3 weeks. (See Section 5.1 Pharmacodynamic properties - Clinical trials Study MO22224 for descriptions of the chemotherapy regimens).
It is recommended that treatment be continued until disease progression.
Cervical cancer
Zirabev is administered in combination with paclitaxel and cisplatin or, if cisplatin is not tolerated or not indicated, paclitaxel and topotecan (see Section 5.1 Pharmacodynamic properties - Clinical trials, study GOG-0240 for further details on the chemotherapy regimens).
The recommended dose of Zirabev is 15 mg/kg of body weight given once every 3 weeks as an IV infusion.
It is recommended that Zirabev treatment be continued until progression of the underlying disease.
For further information refer to the Product Information.
Zirabev (bevacizumab) was approved for the following therapeutic use:
Metastatic colorectal cancer
Zirabev (bevacizumab) in combination with fluoropyrimidine-based chemotherapy is indicated for the treatment of patients with metastatic colorectal cancer.
Locally recurrent or metastatic breast cancer
Zirabev (bevacizumab) in combination with paclitaxel is indicated for the first-line treatment of metastatic breast cancer in patients in whom an anthracycline-based therapy is contraindicated. (see Section 5.1 Pharmacodynamic properties – Clinical trials).
Advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC)
Zirabev (bevacizumab), in combination with carboplatin and paclitaxel, is indicated for first-line treatment of patients with unresectable advanced, metastatic or recurrent, nonsquamous, non- small cell lung cancer.
Advanced and/or metastatic renal cell cancer
Zirabev (bevacizumab) in combination with interferon alfa-2a is indicated for treatment of patients with advanced and/or metastatic renal cell cancer.
Grade IV glioma
Zirabev (bevacizumab) as a single agent, is indicated for the treatment of patients with Grade IV glioma after relapse or disease progression after standard therapy, including chemotherapy.
Epithelial ovarian, fallopian tube or primary peritoneal cancer
Zirabev (bevacizumab) in combination with carboplatin and paclitaxel, is indicated for first-line treatment of patients with advanced (FIGO stages IIIB, IIIC and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer
Zirabev (bevacizumab), in combination with carboplatin and paclitaxel or in combination with carboplatin and gemcitabine, is indicated for the treatment of patients with first recurrence of platinum-sensitive, epithelial ovarian, fallopian tube, or primary peritoneal cancer who have not received prior bevacizumab or other VEGF-targeted angiogenesis inhibitors.
Zirabev (bevacizumab) in combination with paclitaxel, topotecan or pegylated liposomal doxorubicin is indicated for the treatment of patients with recurrent, platinum resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received no more than two prior chemotherapy regimens, and have not received any prior antiangiogenic therapy including bevacizumab.
Cervical Cancer
Zirabev (bevacizumab) in combination with paclitaxel and cisplatin is indicated for the treatment of persistent, recurrent or metastatic carcinoma of the cervix. Zirabev (bevacizumab) in combination with paclitaxel and topotecan is an acceptable alternative where cisplatin is not tolerated or not indicated.
- The bevacizumab (Zirabev) EU-Risk Management Plan (RMP) (version 0.3, date 8 November 2018; data lock point 17 January 2018), with Australian Specific Annex (version 1.1; date 31 May 2019), included with submission PM-2018-03842-1-4, and any subsequent revisions, as agreed with the TGA will be implemented in Australia.
An obligatory component of risk management plans is routine pharmacovigilance. Routine pharmacovigilance includes the submission of periodic safety update reports (PSURs).
Reports are to be provided in line with the current published list of EU reference dates and frequency of submission of PSURs until the period covered by such reports is not less than three years from the date of this approval letter.
The reports are to at least meet the requirements for PSURs as described in the European Medicines Agency's Guideline on Good Pharmacovigilance Practices (GVP) Module VII-periodic safety update report (Rev 1), Part VII.B Structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration.
- Batch testing conditions
- It is a condition of registration that all batches of Zirabev (bevacizumab) imported into Australia must comply with the product details and specifications approved during evaluation and detailed in the Certified Product Details (CPD).
- It is a condition of registration that up to 5 initial batches of Zirabev (bevacizumab) imported into Australia is not released for sale until samples and/or the manufacturer's release data have been assessed and endorsed for release by the TGA Laboratories Branch. Outcomes of laboratory testing are published biannually in the TGA Database of Laboratory Testing Results.
- The sponsor should be prepared to provide product samples, reference materials and documentary evidence as defined by the TGA Laboratories branch. The sponsor must contact Biochemistry.Testing@health.gov.au for specific material requirements related to the batch release testing/assessment of the product. More information on TGA testing of biological medicines is available at https://www.tga.gov.au/publication/testing-biological-medicines.
- This batch release condition will be reviewed and may be modified on the basis of actual batch quality and consistency. This condition remains in place until you are notified in writing of any variation.
- Certified Product Details
The Certified Product Details (CPD), as described in Guidance 7: Certified Product Details of the Australian Regulatory Guidelines for Prescription Medicines (ARGPM), in PDF format, for the above products should be provided upon registration of these therapeutic goods. In addition, an updated CPD should be provided when changes to finished product specifications and test methods are approved in a Category 3 application or notified through a self-assessable change.
The CPD should be emailed to Biochemistry.Testing@health.gov.au as a single PDF document.
- For all injectable products the Product Information must be included with the product as a package insert.